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Functional Recovery of Denervated Skeletal Muscle with Sensory or Mixed Nerve Protection: A Pilot Study
Li, Qing Tian; Zhang, Pei Xun; Yin, Xiao Feng; Han, Na; Kou, Yu Hui; Deng, Jiu Xu; Jiang, Bao Guo
Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection) or sural nerve (sensory protection). The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve. PMID:24244555
Sensory nerves and pancreatitis
Li, Qingfu
Sensory nerves are a kind of nerve that conduct afferent impulses from the periphery receptors to the central nervous system (CNS) and are able to release neuromediators from the activated peripheral endings. Sensory nerves are particularly important for microcirculatory response, and stimulation of pancreatic sensory nerves releases a variety of neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP), etc., leading to neurogenic inflammation characterized as the local vasodilatation and plasma extravasation. Deactivation of sensory nerves often leads to the disturbances of pancreatic microcirculation. Pancreatitis is a common digestive disease that can lead to severe complications and even death if it goes untreated. Experimental studies in animals and tissue analysis in patients with pancreatitis have shown significant changes in sensory nerves supplying the pancreatic gland. Thus making clear the whole mechanism of pancreatitis is essential to treat and cure it. Sensory nerves may have a close correlation with the development of pancreatitis, and knowing more about the role of sensory nerve in pancreatitis is important for the treatment for pancreatitis. This review is aimed to summarize the relationship between sensory nerves and pancreatitis. PMID:25493260
Bladder reinnervation using a primarily motor donor nerve (femoral nerve branches) is functionally superior to using a primarily sensory donor nerve (genitofemoral nerve)
Gomez-Amaya, Sandra M.; Barbe, Mary F.; Brown, Justin M.; Lamarre, Neil S.; Braverman, Alan S.; Massicotte, Vicky S.; Ruggieri, Michael R.
Purpose To determine whether transfer of a primarily motor nerve (Femoral, F) to the anterior vesicle branch of the pelvic nerve (PN) allows more effective bladder reinnervation than a primarily sensory nerve (genitofemoral, GF). Methods Forty-one female mongrel hounds underwent bladder decentralization, decentralization and then bilateral nerve transfer (GFNT and FNT) or were sham/unoperated controls. Decentralization was achieved by bilateral transection of all sacral roots that induce bladder contractions upon electrical stimulation. The retrograde neuronal labeling dye fluorogold was injected into the bladder 3 weeks prior to euthanasia. Results Increased detrusor pressure after direct stimulation of the transferred nerve, lumbar spinal cord or spinal roots was observed in 12/17 GFNT dogs (mean detrusor pressure = 7.6±1.4 cmH2O) and in 9/10 FNT-V dogs (mean detrusor pressure = 11.7±3.1 cm H2O). The mean detrusor pressures after direct electrical stimulation of transferred femoral nerves were statistically significantly greater than after stimulation of the transferred genitofemoral nerves. Retrogradely labeled neurons from the bladder observed in upper lumbar cord segments after GFNT and FNT confirmed bladder reinnervation as did labeled axons at the nerve transfer site. Conclusions While transfer of either a mixed sensory and motor nerve (GFN) or a primarily motor nerve (FN) can reinnervate the bladder, using a primarily motor nerve provides greater return of nerve-evoked detrusor contraction. This surgical approach may be useful for patients with lower motor spinal cord injury to accomplish bladder emptying. PMID:25066874
TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.
Yu, Xiaoyun; Hu, Youtian; Ru, Fei; Kollarik, Marian; Undem, Bradley J; Yu, Shaoyong
Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception. PMID:25591866
Sensory ReEducation after Median Nerve Lesions
Technique for re-educating sensory function after median nerve lesions at the wrist is described.Results of re-education of Twenty-three patients are presented. The functional results are good and belie the traditional view of sensory function after nerve suture.Recent advances in sensory neuro-physiology-are discussed which may explain the successes of this technique.
Nerve Conduction Velocity of Small Components in Human Sensory Nerves
W. Tackmann; R. Minkenberg
Slow conducted components of sensory nerve action potentials were investigated in median and in sural nerves of controls and in patients with peripheral nerve diseases. In the normal group the slow components showed no relation to age which is in contrast to the maximum velocity. In both the median nerve and sural nerve of about 20% of the patients with
Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis
Borbély, Éva; Botz, Bálint; Bölcskei, Kata; Kenyér, Tibor; Kereskai, László; Kiss, Tamás; Szolcsányi, János; Pintér, Erika; Csepregi, Janka Zsófia; Mócsai, Attila; Helyes, Zsuzsanna
Objective The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro–immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology. Methods Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed. Results In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice. Conclusions Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important anti-inflammatory roles at least partially through somatostatin release. PMID:25524130
Natural history of sensory nerve recovery after cutaneous nerve injury following foot and ankle surgery
Bai, Lu; Han, Yan-ni; Zhang, Wen-tao; Huang, Wei; Zhang, Hong-lei
Cutaneous nerve injury is the most common complication following foot and ankle surgery. However, clinical studies including long-term follow-up data after cutaneous nerve injury of the foot and ankle are lacking. In the current retrospective study, we analyzed the clinical data of 279 patients who underwent foot and ankle surgery. Subjects who suffered from apparent paresthesia in the cutaneous sensory nerve area after surgery were included in the study. Patients received oral vitamin B12 and methylcobalamin. We examined final follow-up data of 17 patients, including seven with sural nerve injury, five with superficial peroneal nerve injury, and five with plantar medial cutaneous nerve injury. We assessed nerve sensory function using the Medical Research Council Scale. Follow-up immediately, at 6 weeks, 3, 6 and 9 months, and 1 year after surgery demonstrated that sensory function was gradually restored in most patients within 6 months. However, recovery was slow at 9 months. There was no significant difference in sensory function between 9 months and 1 year after surgery. Painful neuromas occurred in four patients at 9 months to 1 year. The results demonstrated that the recovery of sensory function in patients with various cutaneous nerve injuries after foot and ankle surgery required at least 6 months. PMID:25788928
The near-nerve sensory nerve conduction in tarsal tunnel syndrome
S J Oh; H S Kim; B K Ahmad
The near-nerve sensory nerve conduction in the medial and lateral plantar nerves was studied in 25 cases of tarsal tunnel syndrome. Sensory nerve conduction was abnormal in 24 cases (96%) The most common abnormalities were slow nerve conduction velocities and dispersion phenomenon (prolonged duration of compound nerve action potentials). These two electrophysiological abnormalities are indicative of a focal segmental demyelination
Nerve growth factor decreases in sympathetic and sensory nerves of rats with chronic heart failure.
Xing, Jihong; Lu, Jian; Li, Jianhua
Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6-20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185
Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure
Lu, Jian
Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185
Somatosensory evoked potentials, sensory nerve potentials and sensory nerve conduction in hereditary motor and sensory neuropathy type I
M. Aramideh; J. E. Hoogendijk; C. M. Aalfs; F. E. Posthumus Meyjes; M. Visser; B. W. Ongerboer De Visser
Thirty-nine patients from six families with hereditary motor and sensory neuropathy type I and control subjects were included in this study. A neurological deficit score (NDS) was derived from a neurological examination and compared with neurophysiological test findings. Further, sensory nerve conduction velocities (SNCV) were compared with the motor nerve conduction velocities (MNCV). Five patients whom peaks of N11\\/N13 complex
Leptin-sensitive sensory nerves innervate white fat
Murphy, Keegan T.; Schwartz, Gary J.; Nguyen, Ngoc Ly T.; Mendez, Jennifer M.; Ryu, Vitaly
Leptin, the primary white adipose tissue (WAT) adipokine, is thought to convey lipid reserve information to the brain via the circulation. Because WAT responds to environmental/internal signals in a fat pad-specific (FPS) manner, systemic signals such as leptin would fail to communicate such distinctive information. Saturation of brain leptin transport systems also would fail to convey increased lipid levels beyond that point. WAT possesses sensory innervation exemplified by proven sensory-associated peptides in nerves within the tissue and by viral sensory nerve-specific transneuronal tract tracer, H129 strain of herpes simplex virus 1 labeling of dorsal root ganglia (DRG) pseudounipolar neurons, spinal cord and central sensory circuits. Leptin as a paracrine factor activating WAT sensory innervation could supply the brain with FPS information. Therefore, we tested for and found the presence of the long form of the leptin receptor (Ob-Rb) on DRG pseudounipolar neurons immunohistochemically labeled after injections of Fluorogold, a retrograde tract tracer, into inguinal WAT (IWAT). Intra-IWAT leptin injections (300 ng) significantly elevated IWAT nerve spike rate within 5 min and persisted for at least 30 min. Intra-IWAT leptin injections also induced significant c-Fos immunoreactivity (ir), indicating neural activation across DRG pseudounipolar sensory neurons labeled with Fluorogold IWAT injections. Intraperitoneal leptin injection did not increase c-Fos-ir in DRG or the arcuate nucleus, nor did it increase arcuate signal transducer and activator of transcription 3 phosphorylation-ir. Collectively, these results strongly suggest that endogenous leptin secreted from white adipocytes functions as a paracrine factor to activate spinal sensory nerves innervating the tissue. PMID:23612999
Theobromine inhibits sensory nerve activation and cough.
Usmani, Omar S; Belvisi, Maria G; Patel, Hema J; Crispino, Natascia; Birrell, Mark A; Korbonits, Márta; Korbonits, Dezso; Barnes, Peter J
Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs. PMID:15548587
Tissue Preparation and Immunostaining of Mouse Sensory Nerve Fibers Innervating Skin and Limb Bones
Shepherd, Andrew J.; Mohapatra, Durga P.
Detection and primary processing of physical, chemical and thermal sensory stimuli by peripheral sensory nerve fibers is key to sensory perception in animals and humans. These peripheral sensory nerve fibers express a plethora of receptors and ion channel proteins which detect and initiate specific sensory stimuli. Methods are available to characterize the electrical properties of peripheral sensory nerve fibers innervating the skin, which can also be utilized to identify the functional expression of specific ion channel proteins in these fibers. However, similar electrophysiological methods are not available (and are also difficult to develop) for the detection of the functional expression of receptors and ion channel proteins in peripheral sensory nerve fibers innervating other visceral organs, including the most challenging tissues such as bone. Moreover, such electrophysiological methods cannot be utilized to determine the expression of non-excitable proteins in peripheral sensory nerve fibers. Therefore, immunostaining of peripheral/visceral tissue samples for sensory nerve fivers provides the best possible way to determine the expression of specific proteins of interest in these nerve fibers. So far, most of the protein expression studies in sensory neurons have utilized immunostaining procedures in sensory ganglia, where the information is limited to the expression of specific proteins in the cell body of specific types or subsets of sensory neurons. Here we report detailed methods/protocols for the preparation of peripheral/visceral tissue samples for immunostaining of peripheral sensory nerve fibers. We specifically detail methods for the preparation of skin or plantar punch biopsy and bone (femur) sections from mice for immunostaining of peripheral sensory nerve fibers. These methods are not only key to the qualitative determination of protein expression in peripheral sensory neurons, but also provide a quantitative assay method for determining changes in protein expression levels in specific types or subsets of sensory fibers, as well as for determining the morphological and/or anatomical changes in the number and density of sensory fibers during various pathological states. Further, these methods are not confined to the staining of only sensory nerve fibers, but can also be used for staining any types of nerve fibers in the skin, bones and other visceral tissue. PMID:22314687
Sural nerve defects after nerve biopsy or nerve transfer as a sensory regeneration model for peripheral nerve conduit implantation.
Radtke, C; Kocsis, J D; Reimers, K; Allmeling, C; Vogt, P M
Nerve repair after injury can be effectively accomplished by direct suture approximation of the proximal and distal segments. This is more successful if coadaptation can be achieved without tension. Currently, the gold standard repair of larger deficits is the transplantation of an autologous sensory sural nerve graft. However, a significant disadvantage of this technique is the inevitable donor morbidity (sensory loss, neuroma and scar formation) after harvesting of the sural nerve. Moreover, limitation of autologous donor nerve length and fixed diameter of the available sural nerve are major drawbacks of current autograft treatment. Another approach that was introduced for nerve repair is the implantation of alloplastic nerve tubes made of, for example, poly-L-lactide. In these, nerve stumps of the transected nerves are surgically bridged using the biosynthetic conduit. A number of experimental studies, primarily in rodents, indicate axonal regeneration and remyelination after implantation of various conduits. However, only limited clinical studies with conduit implantation have been performed in acute peripheral nerve injuries particularly on digital nerves. Clinical transfer of animal studies, which can be carefully calibrated for site and extent of injury, to humans is difficult to interpret due to the intrinsic variability in human nerve injuries. This prevents effective quantification of improvement and induces bias in the study. Therefore, standardization of lesion/repair in human studies is warranted. Here we propose to use sural nerve defects, induced due to nerve graft harvesting or from diagnostic nerve biopsies as a model site to enable standardization of nerve conduit implantation. This would help better with the characterization of the implants and its effectiveness in axonal regeneration and remyelination. Nerve regeneration can be assessed, for example, by recovery of sensation, measured non-invasively by threshold to von Frey filaments and cold allodynia. Moreover, the implantation of nerve conduits may not only serve as a model to examine nerve repair, but it could also prevent neuroma formation, which is a major morbidity of sural nerve extraction. PMID:23867139
Observations on the function of nuclear factor kappa B (NF-kappaB) in the survival of adult primary sensory neurons after nerve injury.
Gushchina, Svetlana; Leinster, Veronica; Wu, Dongsheng; Jasim, Avin; Demestre, Maria; Lopez de Heredia, Luis; Michael, Gregory J; Barker, Philip A; Richardson, Peter M; Magoulas, Charalambos
Peripheral nerve transections cause much more neuronal death in embryonic and neonatal dorsal root ganglia (DRG) than in adult DRG. Here we used transgenic approaches to examine the hypothesis that NF-kappaB is an important intrinsic factor of adult DRG neurons for their in vivo capacity to survive after nerve injury. We generated transgenic mice expressing the NF-kappaB super-inhibitor (IkappaBalpha-SI), a multi-mutant form of IkappaBalpha, specifically in adult neurons. Adult DRG neurons in these transgenic animals are not abnormally susceptible to apoptosis after peripheral nerve injury, although there is a significant inhibition in the ability of NF-kappaB to translocate into their nucleus. We investigated the observed lack of NF-kappaB neuroprotective function at the level of NF-kappaB transcriptional activity using transgenic NF-kappaB/LacZ reporter mice. We show that the expression of the NF-kappaB reporter transgene is restricted in naďve and injured DRG neurons. However, NF-kappaB transcriptional activity in adult DRG neurons is evident upon exposure to Trichostatin A (TSA) which is a specific inhibitor of histone deacetylases. Taken together our results illustrate that the functions of NF-kappaB are limited in adult primary sensory neurons due to a transcriptional repression mechanism mediated by histone deacetylases, and that intrinsic neuroprotective factors other than NF-kappaB are responsible for the resistance of adult DRG neurons to apoptosis in response to nerve injury. PMID:19049877
Sensory Nerves Promote Ozone-induced Lung Inflammation in Mice
Genetically manipulated mice exhibiting altered innervation of the airways were used to examine the role of sensory nerves in ozone-induced lung inflammation. Transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secre- tory protein (CCSP) promoter exhibit hyperinnervation of the air- ways by sympathetic and tachykinin-containing sensory nerve fi- bers. Mice carrying a mutation in the low-affinity
Sensory conduction of the sural nerve in polyneuropathy.
Burke, D; Skuse, N F; Lethlean, A K
Using surface electrodes, sensory nerve action potentials (SAP) have been recorded in the proximal segment (mid-calf to lateral malleolus) and the distal segment (lateral malleolus to toe 5) of the sural nerve and in the median nerve in 79 control subjects. The values obtained for the distal segment of the sural nerve varied widely and in seven apparently normal subjects no SAP could be distinguished. In the proximal segment conduction velocities were over 40 m/s and there was no significant change with age, unlike the median nerve in which a highly significant slowing occurred with age. Comparison of the results of sural and median sensory conduction studies in 300 consecutive patients screened for sensory polyneuropathy confirms the value of sural nerve sensory studies as a routine screening test, and confirms the belief that the changes in polyneuropathy are usually more prominent in lower limb nerves. It is therefore suggested that studies of sural sensory conduction form the single most useful test in the diagnosis of sensory polyneuropathy. PMID:4367408
Sensory outcomes of the anterior tongue after lingual nerve repair in oropharyngeal cancer.
Elfring, T T; Boliek, C A; Seikaly, H; Harris, J; Rieger, J M
Primary treatment of oropharyngeal cancer often involves surgical resection and reconstruction of the affected area. However, during base of tongue reconstruction the lingual nerve is often severed on one or both sides, affecting sensation in the preserved tissue of the anterior tongue. The loss of specific tongue sensations could negatively affect a person's oral function and quality of life. The aim of this study was to explore the effects of different types of lingual nerve intervention on sensory function for patients with base of tongue cancer as compared to healthy, age-matched adults. Subjects included 30 patients who had undergone primary oropharyngeal reconstruction with a radial forearm free-flap and 30 matched controls. Sensations tested were temperature, two-point discrimination, light touch, taste, oral stereognosis and texture on the anterior two-thirds of the tongue. Results indicated that type of surgical nerve repair may not have a significant impact on overall sensory outcomes, providing mixed results for either nerve repair technique. Sensations for the nonoperated tongue side and operated side with lingual nerve intact were comparable to matched controls, with mixed outcomes for nerve repair. The poorest sensory outcomes were observed in patients with the lingual nerve severed, while all patients with lingual nerve intervention exhibited deteriorated taste sensation on the affected tongue side. Overall, patients in this study who had undergone oropharyngeal reconstruction with lingual nerve intervention exhibited decreased levels of sensation on the operated tongue side, with minimal differences between types of lingual nerve repair. PMID:21923892
Outcomes of short-gap sensory nerve injuries reconstructed with processed nerve allografts from a multicenter registry study.
Rinker, Brian D; Ingari, John V; Greenberg, Jeffrey A; Thayer, Wesley P; Safa, Bauback; Buncke, Gregory M
Background?Short-gap digital nerve injuries are a common surgical problem, but the optimal treatment modality is unknown. A multicenter database was queried and analyzed to determine the outcomes of nerve gap reconstructions between 5 and 15?mm with processed nerve allograft. Methods?The current RANGER registry is designed to continuously monitor and compile injury, repair, safety, and outcomes data. Centers followed their own standard of care for treatment and follow-up. The database was queried for digital nerve injuries with a gap between 5 and 15?mm reporting sufficient follow-up data to complete outcomes analysis. Available quantitative outcome measures were reviewed and reported. Meaningful recovery was defined by the Medical Research Council Classification (MRCC) scale at S3-S4 for sensory function. Results?Sufficient follow-up data were available for 24 subjects (37 repairs) in the prescribed gap range. Mean age was 43 years (range, 23-81). Mean gap was 11?±?3 (5-15) mm. Time to repair was 13?±?42 (0-215) days. There were 25 lacerations, 8 avulsion/amputations, 2 gunshots, 1 crush injury, and 1 injury of unknown mechanism. Meaningful recovery, defined as S3-S4 on the MRCC scales, was reported in 92% of repairs. Sensory recovery of S3+ or S4 was observed in 84% of repairs. Static 2PD was 7.1?±?2.9?mm (n?=?19). Return to light touch was observed in 23 out of 32 repairs reporting Semmes-Weinstein monofilament outcomes (SWMF). There were no reported nerve adverse events. Conclusion?Sensory outcomes for processed nerve allografts were equivalent to historical controls for nerve autograft and exceed those of conduit. Processed nerve allografts provide an effective solution for short-gap digital nerve reconstructions. PMID:25893633
Nerve injury induces the expression of syndecan-1 heparan sulfate proteoglycan in primary sensory neurons.
Murakami, K; Tanaka, T; Bando, Y; Yoshida, S
Heparan sulfate proteoglycans (HSPGs) have important functions in development of the central nervous system; however, their functions in nerve injury are not yet fully understood. We previously reported the expression of syndecan-1, a type of HSPG, in cranial motor neurons after nerve injury, suggesting the importance of syndecan-1 in the pathology of motor nerve injury. In this study, we examined the expression of syndecan-1, a type of HSPG, in primary sensory neurons after nerve injury in mice. Sciatic nerve axotomy strongly induced the expression of syndecan-1 in a subpopulation of injured dorsal root ganglion (DRG) neurons, which were small in size and had CGRP- or isolectin B4-positive fibers. Syndecan-1 was also distributed in the dorsal horn of the spinal cord ipsilateral to the axotomy, and located on the membrane of axons in lamina II of the dorsal horn. Not only sciatic nerve axotomy, infraorbital nerve axotomy also induced the expression of syndecan-1 in trigeminal ganglion neurons. Moreover, syndecan-1 knockdown in cultured DRG neurons induced a shorter neurite extension. These results suggest that syndecan-1 expression in injured primary sensory neurons may have functional roles in nerve regeneration and synaptic plasticity, resulting in the development of neuropathic pain. PMID:26002314
Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions
V Dimitriadou; A Rouleau; M. D Trung Tuong; G. J. F Newlands; H. R. P Miller; G Luffau; J.-C Schwartz; M Garbarg
In this study, we have characterized the phenotype of mast cells in rat dura mater and their topological and functional relationships with C-fibers in normal and inflammatory conditions. Three mast cell populations with different size, morphology and localization were characterized by their content of specific neutral serine proteases. They showed immunoreactivity corresponding to rat mast cell protease I, rat mast
A reversible functional sensory neuropathy model.
Danigo, Aurore; Magy, Laurent; Richard, Laurence; Sturtz, Franck; Funalot, Benoît; Demiot, Claire
Small-fiber neuropathy was induced in young adult mice by intraperitoneal injection of resiniferatoxin (RTX), a TRPV1 agonist. At day 7, RTX induced significant thermal and mechanical hypoalgesia. At day 28, mechanical and thermal nociception were restored. No nerve degeneration in skin was observed and unmyelinated nerve fiber morphology and density in sciatic nerve were unchanged. At day 7, substance P (SP) was largely depleted in dorsal root ganglia (DRG) neurons, although calcitonin gene-related peptide (CGRP) was only moderately depleted. Three weeks after, SP and CGRP expression was restored in DRG neurons. At the same time, CGRP expression remained low in intraepidermal nerve fibers (IENFs) whereas SP expression had improved. In summary, RTX induced in our model a transient neuropeptide depletion in sensory neurons without nerve degeneration. We think this model is valuable as it brings the opportunity to study functional nerve changes in the very early phase of small fiber neuropathy. Moreover, it may represent a useful tool to study the mechanisms of action of therapeutic strategies to prevent sensory neuropathy of various origins. PMID:24792390
Reduced intraepidermal nerve fiber density in HIV-associated sensory
Steinbach, Joe Henry
severity and progression of HIV disease. Background: SN affects 30% of individuals with AIDS, and treatment in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory
Transient receptor potential channels on sensory nerves.
Eid, S R; Cortright, D N
The somatosensory effects of natural products such as capsaicin, mustard oil, and menthol have been long recognized. Over the last decade, the identification of transient receptor potential (TRP) channels in primary sensory neurons as the targets for these agents has led to an explosion of research into the roles of "thermoTRPs" TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8 in nociception. In concert, through the efforts of many industrial and academic teams, a number of agonists and antagonists of these channels have been discovered, paving the way for a better understanding of sensory biology and, potentially, for novel treatments for diseases. PMID:19655110
The distal sensory nerve action potential as a diagnostic tool for the differentiation of lesions in dorsal roots and peripheral nerves
R. Benecke; B. Conrad
On the basis of the conception that, in preganglionic lesions, peripheral sensory nerve fibers should remain intact, the question arises whether evaluation of distal sensory nerve action potentials can be helpful in differentiating between cervical dorsal root and peripheral nerve lesions. Amplitudes of sensory nerve action potentials (SNAP) and corresponding distal sensory conduction velocities (SCV) of the median and ulnar
Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries
He, Bo; Zhu, Zhaowei; Zhu, Qingtang; Zhou, Xiang; Zheng, Canbin; Li, Pengliang; Zhu, Shuang; Liu, Xiaolin; Zhu, Jiakai
OBJECTIVE: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES: The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION: The following types of article were selected: (1) clinical trials describing the repair of median, ulnar, radial, and digital nerve injuries published in English; and (2) studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to investigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES: Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3+ or S4. RESULTS: Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were independent predictors of outcome after the repair of nerve injuries (P < 0.05), and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION: Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up. PMID:25206870
Transient Receptor Potential Channels on Sensory Nerves
S. R. Eid; D. N. Cortright
\\u000a The somatosensory effects of natural products such as capsaicin, mustard oil, and menthol have been long recognized. Over\\u000a the last decade, the identification of transient receptor potential (TRP) channels in primary sensory neurons as the targets\\u000a for these agents has led to an explosion of research into the roles of "thermoTRPs" TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and\\u000a TRPM8 in nociception.
C-peptide improves autonomic nerve function in IDDM patients
B. L. Johansson; K. Borg; E. Fernqvist-Forbes; T. Odergren; S. Remahl; J. Wahren
Summary In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during
Acrolein depletes the neuropeptides CGRP and substance P in sensory nerves in rat respiratory tract.
Springall, D R; Edginton, J A; Price, P N; Swanston, D W; Noel, C; Bloom, S R; Polak, J M
The mammalian respiratory tract is densely innervated by autonomic and sensory nerves around airways and blood vessels. Subsets of these nerves contain a number of putative neurotransmitter peptides, such as substance P and calcitonin gene-related peptide (CGRP) in sensory nerves and vasoactive intestinal polypeptide (VIP), possibly serving autonomic functions. CGRP is also found in endocrine cells in rat airway epithelium. These peptides are all pharmacologically potent effectors of bronchial and vascular smooth muscle and bronchial secretion. Their functions in vivo are less well established. We have therefore examined the effects of inhaled acrolein, a sensory irritant, on three pulmonary neuropeptides: CGRP, substance P, and VIP. Groups of rats (n = 3 each) were exposed for 10 min to acrolein in air (Ct = 510, 1858, and 5693 mg.min/m3) or to air alone. Fifteen minutes later they were killed (pentabarbitone IP) and their respiratory tracts were dissected and fixed in 0.4% p-benzoquinone solution. Cryostat sections were stained by indirect immunofluorescence for a general nerve marker (PGP 9.5) and neuropeptides. The acrolein-treated animals had a dose-related decrease in tracheal substance P- and CGRP-immunoreactive nerve fibers compared with controls. No change was seen in total nerve fiber distribution and number (PGP 9.5) or VIP immunoreactivity, nor in CGRP-immunoreactive epithelial endocrine cells. It is concluded that the rat tracheal peptidergic nerves are a sensitive indicator of inhaled irritant substances. Their reduced immunoreactivity may be because of a release of sensory neuropeptides that could play a role in the physiological response to irritant or toxic compounds. Images FIGURE 4. a FIGURE 4. b FIGURE 5. a FIGURE 5. b FIGURE 6. a FIGURE 6. b FIGURE 7. a FIGURE 7. b FIGURE 7. c FIGURE 8. a FIGURE 8. b PMID:1696540
The effect of surgical medicaments on peripheral nerve function
A. R. Loescher; P. P. Robinson
Surgical medicaments are often placed in close proximity to peripheral nerves and maybe responsible for some postoperative sensory disturbances. In this study we investigated the effect of four medicaments - BIPP, (bismuth iodoform paraffin paste), Whitehead's varnish (compound iodoform paint), Surgicel (oxidized regenerated cellulose) and Carnoy's solution (ethanol, chloroform and acetic acid) - on peripheral nerve function. The experiments were
Noninvasive Peroneal Sensory and Motor Nerve Conduction Recordings in the Rabbit Distal Hindlimb: Feasibility, Variability and Neuropathy Measure
Hotson, John R.
The peroneal nerve anatomy of the rabbit distal hindlimb is similar to humans, but reports of distal peroneal nerve conduction studies were not identified with a literature search. Distal sensorimotor recordings may be useful for studying rabbit models of length-dependent peripheral neuropathy. Surface electrodes were adhered to the dorsal rabbit foot overlying the extensor digitorum brevis muscle and the superficial peroneal nerve. The deep and superficial peroneal nerves were stimulated above the ankle and the common peroneal nerve was stimulated at the knee. The nerve conduction studies were repeated twice with a one-week intertest interval to determine measurement variability. Intravenous vincristine was used to produce a peripheral neuropathy. Repeat recordings measured the response to vincristine. A compound muscle action potential and a sensory nerve action potential were evoked in all rabbits. The compound muscle action potential mean amplitude was 0.29 mV (SD ± 0.12) and the fibula head to ankle mean motor conduction velocity was 46.5 m/s (SD ± 2.9). The sensory nerve action potential mean amplitude was 22.8 ?V (SD ± 2.8) and the distal sensory conduction velocity was 38.8 m/s (SD ± 2.2). Sensorimotor latencies and velocities were least variable between two test sessions (coefficient of variation ?=? 2.6–5.9%), sensory potential amplitudes were intermediate (coefficient of variation ?=? 11.1%) and compound potential amplitudes were the most variable (coefficient of variation ?=?19.3%). Vincristine abolished compound muscle action potentials and reduced sensory nerve action potential amplitudes by 42–57% while having little effect on velocity. Rabbit distal hindlimb nerve conduction studies are feasible with surface recordings and stimulation. The evoked distal sensory potentials have amplitudes, configurations and recording techniques that are similar to humans and may be valuable for measuring large sensory fiber function in chronic models of peripheral neuropathies. PMID:24658286
A Randomized, Controlled, Open-Label Study of the Long-Term Effects of NGX-4010, a High-Concentration Capsaicin Patch, on Epidermal Nerve Fiber Density and Sensory Function in Healthy Volunteers
William R. Kennedy; Geertrui F. Vanhove; Shiao-ping Lu; Jeffrey Tobias; Keith R. Bley; David Walk; Gwen Wendelschafer-Crabb; Donald A. Simone; Mona M. Selim
Desensitization of nociceptive sensory nerve endings is the basis for the therapeutic use of capsaicin in neuropathic pain syndromes. This study evaluated the pharmacodynamic effects of a single 60-minute application of NGX-4010, a high-concentration (8% w\\/w) capsaicin patch, on both thighs of healthy volunteers. Epidermal nerve fiber (ENF) density and quantitative sensory testing (QST) using thermal, tactile, and sharp mechanical-pain
Regeneration of sensory but not motor axons following visceral nerve injury.
Payne, Sophie C; Belleville, Philip J; Keast, Janet R
Following peripheral nerve injury, restoration of function may occur via the regeneration of injured axons or compensatory sprouting of spared axons. Injury to visceral nerves that control urogenital organs is a common consequence of pelvic surgery, however their capacity to reinnervate organs is poorly understood. To determine if and how sensory and motor connections to the bladder are re-established, a novel surgical model of visceral nerve injury was performed unilaterally in adult male Wistar rats. Bladder-projecting motor and sensory neurons in pelvic ganglia and lumbosacral dorsal root ganglia, respectively, were identified and characterised by retrograde tracing and immunofluorescence. Application of tracers ipsi- and contralateral to injury distinguished the projection pathways of new connections in the bladder. In naive animals, the majority of sensory and motor neurons project ipsilaterally to the bladder, while ~20 % project contralaterally and ~5 % bilaterally. Injured axons of motor neurons were unable to regenerate by 4weeks after transection. In contrast, by this time many injured sensory neurons regrew axons to reform a substantial plexus within the detrusor and suburothelial tissues. These regeneration responses were also indicated by upregulation of activating transcription factor-3 (ATF-3), which was sustained in motor neurons but transient in sensory bladder-projecting neurons. Axotomy had little or no effect on the survival of bladder-projecting sensory and motor neurons. We also found evidence that uninjured motor and sensory neurons develop additional projections to the denervated bladder tissue and return connectivity, likely by undergoing compensatory growth. In conclusion, our results show that visceral sensory and motor neurons have a different capacity to regenerate axons following axotomy, however in both components of the circuit uninjured bladder neurons spontaneously grow new axon collaterals to replace the lost terminal field within the organ. For a full functional recovery, understanding the environmental and cellular mechanisms that reduce the ability of pelvic ganglion cells to undergo axonal regeneration is needed. PMID:25725351
Motor and sensory nerve conduction velocities in Yucatan minipigs
C Hort-Legrand; L Noah; E Mériguet; D Mésangeau
Summary Motor and\\/or sensory conduction velocities are used to assess peripheral nervous system disorders. Although the miniature pig represents a model of choice for long-term pharmacological experimentation, no study has so far been reported on this model in relation to the measurement of nerve conduction velocities. We developed the present technique and applied it to 34 3-18-month-old Yucatan minipigs. Motor
Sensory Nerve Conduction in Demyelinating and Axonal Guillain-Barré Syndromes
Satoshi Kuwabara; Kazue Ogawara; Sonoko Misawa; Keiko Mizobuchi; Jia-Ying Sung; Yukiko Kitano; Masahiro Mori; Takamichi Hattori
Guillain-Barré syndrome is divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) based on motor nerve conduction studies. We investigated whether sensory nerve conduction studies contribute to the electrodiagnosis of AIDP and AMAN. In consecutive 59 patients with AIDP (n = 26) or AMAN (n = 33), results of sensory nerve conduction studies in the median,
Functional weakness and sensory disturbance
Stone, J; Zeman, A; Sharpe, M
In the diagnosis of functional weakness and sensory disturbance, positive physical signs are as important as absence of signs of disease. Motor signs, particularly Hoover's sign, are more reliable than sensory signs, but none should be used in isolation and must be interpreted in the overall context of the presentation. It should be borne in mind that a patient may have both a functional and an organic disorder. PMID:12185152
Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.
Hodges, Gary J; Traeger, J Andrew; Tang, Tri; Kosiba, Wojciech A; Zhao, Kun; Johnson, John M
Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29 degrees C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 +/- 55%, LA only; 42 +/- 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 +/- 8 and 6 +/- 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 +/- 4 and 46 +/- 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (-26 +/- 8 and -22 +/- 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC. PMID:17468334
Sensory nerves and nitric oxide contribute to reflex cutaneous vasodilation in humans.
Wong, Brett J
We tested the hypothesis that inhibition of cutaneous sensory nerves would attenuate reflex cutaneous vasodilation in response to an increase in core temperature. Nine subjects were equipped with four microdialysis fibers on the forearm. Two sites were treated with topical anesthetic EMLA cream for 120 min. Sensory nerve inhibition was verified by lack of sensation to a pinprick. Microdialysis fibers were randomly assigned as 1) lactated Ringer (control); 2) 10 mM nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase; 3) EMLA + lactated Ringer; and 4) EMLA + L-NAME. Laser-Doppler flowmetry was used as an index of skin blood flow, and blood pressure was measured via brachial auscultation. Subjects wore a water-perfused suit, and oral temperature was monitored as an index of core temperature. The suit was perfused with 50°C water to initiate whole body heat stress to raise oral temperature 0.8°C above baseline. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVC(max)). There was no difference in CVC between control and EMLA sites (67 ± 5 vs. 69 ± 6% CVC(max)), but the onset of vasodilation was delayed at EMLA compared with control sites. The L-NAME site was significantly attenuated compared with control and EMLA sites (45 ± 5% CVC(max); P < 0.01). Combined EMLA + L-NAME site (25 ± 6% CVC(max)) was attenuated compared with control and EMLA (P < 0.001) and L-NAME only (P < 0.01). These data suggest cutaneous sensory nerves contribute to reflex cutaneous vasodilation during the early, but not latter, stages of heat stress, and full expression of reflex cutaneous vasodilation requires functional sensory nerves and NOS. PMID:23408029
Sensory nerve conduction in the upper limbs at various stages of diabetic neuropathy 1
P. Noël
In 59 diabetic patients, sensory nerve potentials were recorded at various sites along the course of the median nerve. Pathological responses were characterized by reduced amplitude, desynchronization and decreased conduction velocity (CV). Four groups of patients with increasingly severe nerve dysfunction were distinguished. The presence and severity of clinical neuropathy in the upper limbs could be related to decreased maximal
Photostimulation of sensory neurons of the rat vagus nerve
NASA Astrophysics Data System (ADS)
Rhee, Albert Y.; Li, Gong; Wells, Jonathon; Kao, Joseph P. Y.
We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-?m output of a diode laser, delivered through a 200-?m silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca 2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca 2+ indicator, to monitor the rise in intracellular Ca 2+ concentration ([Ca 2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca 2+]i (referred to as Ca 2+ transients). Consistent with the Ca 2+ transients arising from influx of Ca 2+, identical photostimulation failed to evoke Ca 2+ responses in the absence of extracellular Ca 2+. Furthermore, the photo-induced Ca 2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.
Schwann Cells Seeded in Acellular Nerve Grafts Improve Functional Recovery
Jesuraj, Nithya J.; Santosa, Katherine B.; MacEwan, Matthew R.; Moore, Amy M.; Kasukurthi, Rahul; Ray, Wilson Z.; Flagg, Eric R.; Hunter, Daniel A.; Borschel, Gregory H.; Johnson, Philip J.; Mackinnon, Susan E.; Sakiyama-Elbert, Shelly E.
Introduction This study evaluated whether Schwann cells (SCs) from different nerve sources transplanted into cold-preserved acellular nerve grafts (CP-ANGs) would improve functional regeneration compared to nerve isografts. Methods SCs isolated and expanded from motor and sensory branches of rat femoral and sciatic nerves were seeded into 14mm CP-ANGs. Growth factor expression, axonal regeneration, and functional recovery were evaluated in a14 mm rat sciatic injury model and compared to isografts. Results At 14 days, motor or sensory-derived SCs increased expression of growth factors in CP-ANGs versus isografts. After 42 days, histomorphometric analysis found CP-ANGs with SCs and isografts had similar numbers of regenerating nerve fibers. At 84 days, muscle force generation was similar for CP-ANGs with SCs and isografts. SC source did not affect nerve fiber counts or muscle force generation. Discussion SCs transplanted into CP-ANGs increase functional regeneration to isograft levels; however SC nerve source did not have an effect. PMID:23625513
Ultrasound-guided Selective Sensory Nerve Block for Wide-awake Forearm Tendon Reconstruction
Nakanishi, Yasuaki; Kobata, Yasunori; Shimizu, Takamasa; Kira, Tsutomu; Onishi, Tadanobu; Hayami, Naoki; Tanaka, Yasuhito
Background: Wide-awake hand surgery is useful for tendon reconstruction because surgeons can observe the actual movement of the reconstructed tendons during the surgery. We hypothesized that accurate ultrasound-guided injection of local anesthetics into the sensory nerves contributes to reliable analgesia with a relatively small amount of anesthetic. Methods: We enrolled 8 patients who underwent forearm tendon transfer. Three patients underwent reconstruction of flexor tendon ruptures in zones 4 and 5, 3 underwent opponensplasty, and 2 underwent multiple tendon transfers according to Brand's procedure. All patients underwent ultrasound-guided injection of ropivacaine to each sensory nerve branch of the upper arm and forearm and into the subfascial layer of the forearm. The mean amount of total ropivacaine was 193?mg. Results: In 7 of the 8 patients, we confirmed adequate active contraction of the flexor or extensor muscles during surgery. The expected active motion of the flexor pollicis longus was not found in 1 patient during surgery because the effect of the anesthetic had spread too widely, involving the motor branch of the median nerve. Two patients required additional infiltration of 2–3?mL of local anesthetic because of local wound pain. All patients gained satisfactory function of the transferred tendons after the surgery, and no remarkable perioperative complications related to local anesthetic systemic toxicity occurred. Conclusions: Selective administration of an anesthetic to the sensory nerve branches and subfascial layer enables the performance of wide-awake forearm tendon surgery. The ultrasound-guided injection technique provides safe and effective regional anesthesia for wide-awake surgery.
Retrograde changes in motor and sensory conduction velocity after nerve injury.
Stöhr, M; Schumm, F; Reill, P
Nerve section is followed by a reduction of motor and sensory conduction velocity in the proximal segment of the injured nerve. This reduction of velocity is associated with retrograde changes in fiber size. If reinnervation does not occur within the next 1 1/2--2 years, retrograde degeneration of nerve fibers results, and the amplitude of the evoked nerve potential in the proximal segment of the injured nerve decreases. This retrograde degeneration is probably significant in view of the poor results frequently obtained after nerve transplantation which is carried out too late. PMID:67191
Selective Targeting of TRPV1 Expressing Sensory Nerve Terminals in the Spinal Cord for Long Lasting Analgesia
Sikand, Parul; Parihar, Arti; Evans, M. Steven; Premkumar, Louis S.
Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain. PMID:19753113
Changes in sensory activity of ocular surface sensory nerves during allergic keratoconjunctivitis.
Acosta, M Carmen; Luna, Carolina; Quirce, Susana; Belmonte, Carlos; Gallar, Juana
Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. Blinking and tearing rate were measured. Spontaneous and stimulus-evoked (mechanical, thermal, chemical) impulse activity was recorded from mechanonociceptor, polymodal nociceptor and cold corneoscleral sensory afferent fibers. After a single (day 14) or repeated daily exposures to the allergen during the following 3 to 4days, tearing and blinking rate increased significantly. Also, sensitization was observed in mechanonociceptors (transient reduction of mechanical threshold only on day 14) and in polymodal nociceptors (sustained enhancement of the impulse response to acidic stimulation). In contrast, cold thermoreceptors showed a significant decrease in basal ongoing activity and in the response to cooling. Treatment with the TRPV1 and TRPA1 blockers capsazepine and HC-030031 reversed the augmented blinking. Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes. PMID:23867735
Sensory nerve conduction velocities in the cutaneous afferents of the ulnar and peroneal nerves of the dog: Tissue temperature-dependent reference ranges
A. Miyamoto; A. Sumi; Y. Ishido; T. Nakano; M. Yahagi; S. Inada
Sensory nerve conduction velocities in the cutaneous afferents of the ulnar and peroneal nerves of the neurologically normal adult dog were determined by stimulation at stimulus intensities of 15, 20 and 25 V through subcutaneously placed electrodes and by the averaged evoked response technique. Stimulus intensities of 15 V for the ulnar nerve and 20 V for the peroneal nerve
Sensory and motor maximum nerve conduction velocity in the peripheral and central nervous system of the beagle dog
U. Schaeppi; M. Teste; U. Siegenthaler
Sensory maximum nerve conduction velocity (MNCV) and motor MNCV were monitored in altogether 14 beagle dogs anaesthetized with pentobarbital. Sensory MNCV was determined by averaging cortically evoked potentials from somatosensory area I (SS I) in response to repeated electrical stimulation of digital paw pads, tibial nerve at calcaneus or sciatic nerve at trochanter.
Peripheral motor and sensory nerve conduction studies in normal infants and children
Antonio Garc??a; Jesús Calleja; Francisco M. Antol??n; José Berciano
Objective: There are few data on electrophysiological data of motor and sensory fibres during nerve maturation. The aim of this study is to investigate the evolution of nerve conduction in the upper and lower limbs during the first years of life.Methods: The study comprised 92 normal infants and children aged from 1 week to 6 years. Using surface electrodes, the
Comparison of orthodromic and antidromic sensory nerve conduction velocity measurements in the carpal tunnel syndrome
W. Tackmann; H. E. Kaeser; H. G. Magun
Orthodromic and antidromic nerve conduction velocities were determined in sensory median nerve fibres from digit to palm and from palm to wrist in patients with the carpal tunnel syndrome. In a large number of subjects the carpal tunnel syndrome could be detected only when the palm-to-wrist segment was investigated.
Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA
C. Chalar; A. Richeri; L. Viettro; R. Chávez-Genaro; P. Bianchimano; N. M. Marmol; K. Crutcher; G. Burnstock; T. Cowen; M. M. Brauer
In the present study we investigated the effects of infantile\\/prepubertal chronic oestrogen treatment, chemical sympathectomy with guanethidine and combined sympathectomy and chronic oestrogen treatment on developing sensory nerves of the rat uterus. Changes in sensory innervation were assessed quantitatively on uterine cryostat tissue sections stained for calcitonin gene-related peptide (CGRP). Uterine levels of NGF protein, using immunohistochemistry and ELISA, and
Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas
NASA Technical Reports Server (NTRS)
Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.
Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.
Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas.
Macias, M Y; Lehman, C T; Sanger, J R; Riley, D A
Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies. PMID:9843078
Prevalence of subclinical neuropathy in diabetic patients: assessment by study of conduction velocity distribution within motor and sensory nerve fibres
Pierluigi Bertora; Pierluigi Valla; Elisabetta Dezuanni; Maurizio Osio; Davide Mantica; Maurizio Bevilacqua; Guido Norbiato; Mario Riccardo Caccia; Alfonso Mangoni
Nerve conduction velocity distribution (CVD) study is a newly-developed electrodiagnostic method for detecting alterations\\u000a in the composition of nerve fibres according to their conduction velocity. The presence of subclinical neuropathy was evaluated\\u000a in 138 diabetic patients by CVD study of four motor nerves (external popliteal and ulnar nerves bilaterally) and two sensory\\u000a nerves (median nerve bilaterally), and the data obtained
Ultrasound of radial, ulnar, median, and sciatic nerves in healthy subjects and patients with hereditary motor and sensory neuropathies
Oliver Heinemeyer; Carl D Reimers
This study was conducted to evaluate the capability of ultrasonography to visualize extremity nerves. Fifty healthy women and men and 10 patients suffering with hereditary motor and sensory neuropathy (HMSN) were examined. The radial nerve lateral to the humerus, ulnar nerve distal to the cubital tunnel, median nerve in the middle of the forearm and proximal to the palmar crease,
Bloom, Aaron P.; Jimenez-Andrade, Juan M.; Taylor, Reid N.; Castańeda-Corral, Gabriela; Kaczmarska, Magdalena J.; Freeman, Katie T.; Coughlin, Kathleen A.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.
Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP+) sensory nerve fibers. Nearly all CGRP+ nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+) and growth associated protein-43 (GAP43+). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP+ / TrkA+ / GAP43+ sensory nerve fibers. PMID:21497141
Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves.
Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo
The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO(3) per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb's LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 ?m) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb. PMID:21197231
Effect of helium-neon laser irradiation on peripheral sensory nerve latency
Snyder-Mackler, L.; Bork, C.E.
The purpose of this randomized, double-blind study was to determine the effect of a helium-neon (He-Ne) laser on latency of peripheral sensory nerve. Forty healthy subjects with no history of right upper extremity pathological conditions were assigned to either a Laser or a Placebo Group. Six 1-cm2 blocks along a 12-cm segment of the subjects' right superficial radial nerve received 20-second applications of either the He-Ne laser or a placebo. We assessed differences between pretest and posttest latencies with t tests for correlated and independent samples. The Laser Group showed a statistically significant increase in latency that corresponded to a decrease in sensory nerve conduction velocity. Short-duration He-Ne laser application significantly increased the distal latency of the superficial radial nerve. This finding provides information about the mechanism of the reported pain-relieving effect of the He-Ne laser.
The correlation between sensory nerve conduction velocities and three metabolic indices in rats treated with streptozotocin
P. O. O. Julu
Summary The fastest conduction velocities of the myelinated (A) and unmyelinated (C) sensory nerve fibres were measured in the saphenous nerves of rats made diabetic up to 5 weeks previously by injection of streptozotocin. The conduction velocity of the fastest A-alpha fibres in treated rats fell by 25% compared to control rats. The effect on the slow A-delta fibres was small
Sensory nerve conduction studies of the L-1\\/L-2 dorsal rami
Amrit P. Singh; Hillel M. Sommer
Objective: This report describes a technique for performing sensory nerve conduction studies of the lateral cutaneous branches of the dorsal rami of the L-1\\/L-2 nerve roots for use in the evaluation of unilateral low back pain without lower limb referral.Subjects: Eleven healthy adult volunteers (9 men and 2 women) ranging in age from 25 to 36 years with no current
Assessment of Sensory Nerve Conduction in Carpal Tunnel Syndrome before, during and after Operation
Sensory conduction velocities of the median nerve before, during and after operation were compared in nine patients with carpal tunnel syndrome and four controls, in order to evaluate the prognostic value of the pre-operative and intra-operative findings.Sensory conduction velocity was higher after operation than before in all patients (mean difference 31.33%), but not in control subjects. One patient showed a
Characteristics of patients with sensory neuropathy diagnosed with abnormal small nerve fibres on skin biopsy.
De Sousa, E A; Hays, A P; Chin, R L; Sander, H W; Brannagan, T H
Clinical, laboratory and electrodiagnostic (EDX) characteristics of 62 patients with sensory neuropathy with abnormal skin biopsies were reviewed. Reduced epidermal nerve fibre density (ENFD) was seen in 71% and morphological changes with normal ENFD were seen in 29% of the patients. Patients with small fibre sensory neuropathy may have associated large fibre loss undetected by routine EDX. Identified associations included abnormal glucose metabolism, Lyme vaccination, monoclonal gammopathy, vitamin B12 deficiency, coeliac disease, and diseases of the connective tissue, inflammatory bowel and thyroid. Sensory neuropathy remained undetermined in 50% of the patients. PMID:16844956
Sensory nerve conduction in branches of common interdigital nerves: a new technique for normal controls and patients with morton's neuroma.
Uludag, Burhanettin; Tataroglu, Cengiz; Bademkiran, Fikret; Uludag, Irem Fatma; Ertekin, Cumhur
In this article, a new electrodiagnostic approach is described for patients with Morton's neuroma. The new method is based on the anatomic fact that the two branches of the common plantar interdigital nerves innervate the lateral side of one toe and the medial side the next one. This study included 20 normal subjects (aged 28-58 years, 10 men and 10 women) and 4 patients with Morton's neuroma (aged 44-52 years, 4 women). The branches of adjacent common plantar interdigital nerves that innerve one toe were stimulated superficially and separately with half of one toe covered with a piece of medical tape. The recordings were obtained on the posterior tibial nerve at the medial malleolus with needle electrodes. Thus, the difference in latencies of obtained sensory nerve action potentials on the posterior tibial nerve with needle electrode was measured. From normal subjects' data, it was determined that a latency difference value of above 0.17 milliseconds (mean +/- 2.5 SD) in one toe was abnormal. All of the patients with Morton's neuroma showed abnormal interlatency difference values. This new method, which we have developed, is more sensitive, simple to use, does not require extra equipment, and does not cause excessive pain. We suggest that interlatency difference between branches of the common plantar interdigital nerves is a useful and sensitive method for the diagnosis of Morton's neuroma. PMID:20479659
Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C
Hadley, Stephen H.; Bahia, Parmvir K.
Airway sensory nerve excitability is a key determinant of respiratory disease-associated reflexes and sensations such as cough and dyspnea. Inflammatory signaling modulates mitochondrial function and produces reactive oxygen species (ROS). Peripheral terminals of sensory nerves are densely packed with mitochondria; thus, we hypothesized that mitochondrial modulation would alter neuronal excitability. We recorded action potential firing from the terminals of individual bronchopulmonary C-fibers using a mouse ex vivo lung-vagal ganglia preparation. C-fibers were characterized as nociceptors or non-nociceptors based upon conduction velocity and response to transient receptor potential (TRP) channel agonists. Antimycin A (mitochondrial complex III Qi site inhibitor) had no effect on the excitability of non-nociceptors. However, antimycin A increased excitability in nociceptive C-fibers, decreasing the mechanical threshold by 50% and increasing the action potential firing elicited by a P2X2/3 agonist to 270% of control. Antimycin A–induced nociceptor hyperexcitability was independent of TRP ankyrin 1 or TRP vanilloid 1 channels. Blocking mitochondrial ATP production with oligomycin or myxothiazol had no effect on excitability. Antimycin A–induced hyperexcitability was dependent on mitochondrial ROS and was blocked by intracellular antioxidants. ROS are known to activate protein kinase C (PKC). Antimycin A–induced hyperexcitability was inhibited by the PKC inhibitor bisindolylmaleimide (BIM) I, but not by its inactive analog BIM V. In dissociated vagal neurons, antimycin A caused ROS-dependent PKC translocation to the membrane. Finally, H2O2 also induced PKC-dependent nociceptive C-fiber hyperexcitability and PKC translocation. In conclusion, ROS evoked by mitochondrial dysfunction caused nociceptor hyperexcitability via the translocation and activation of PKC. PMID:24642367
Sensory nerve terminal mitochondrial dysfunction induces hyperexcitability in airway nociceptors via protein kinase C.
Hadley, Stephen H; Bahia, Parmvir K; Taylor-Clark, Thomas E
Airway sensory nerve excitability is a key determinant of respiratory disease-associated reflexes and sensations such as cough and dyspnea. Inflammatory signaling modulates mitochondrial function and produces reactive oxygen species (ROS). Peripheral terminals of sensory nerves are densely packed with mitochondria; thus, we hypothesized that mitochondrial modulation would alter neuronal excitability. We recorded action potential firing from the terminals of individual bronchopulmonary C-fibers using a mouse ex vivo lung-vagal ganglia preparation. C-fibers were characterized as nociceptors or non-nociceptors based upon conduction velocity and response to transient receptor potential (TRP) channel agonists. Antimycin A (mitochondrial complex III Qi site inhibitor) had no effect on the excitability of non-nociceptors. However, antimycin A increased excitability in nociceptive C-fibers, decreasing the mechanical threshold by 50% and increasing the action potential firing elicited by a P2X2/3 agonist to 270% of control. Antimycin A-induced nociceptor hyperexcitability was independent of TRP ankyrin 1 or TRP vanilloid 1 channels. Blocking mitochondrial ATP production with oligomycin or myxothiazol had no effect on excitability. Antimycin A-induced hyperexcitability was dependent on mitochondrial ROS and was blocked by intracellular antioxidants. ROS are known to activate protein kinase C (PKC). Antimycin A-induced hyperexcitability was inhibited by the PKC inhibitor bisindolylmaleimide (BIM) I, but not by its inactive analog BIM V. In dissociated vagal neurons, antimycin A caused ROS-dependent PKC translocation to the membrane. Finally, H2O2 also induced PKC-dependent nociceptive C-fiber hyperexcitability and PKC translocation. In conclusion, ROS evoked by mitochondrial dysfunction caused nociceptor hyperexcitability via the translocation and activation of PKC. PMID:24642367
Capsaicin Combined with Local Anesthetics Preferentially Prolongs Sensory/Nociceptive Block in Rat Sciatic Nerve
Binshtok, Alexander M.; Wang, Chi-Fei; Hevelone, Nathanael D.; Bean, Bruce P.; Woolf, Clifford J.; Wang, Ging Kuo
Background Transient receptor potential vanilloid 1 channels integrate nociceptive stimuli and are predominantly expressed by unmyelinated C-fiber nociceptors, but not low-threshold mechanoreceptive sensory or motor fibers. A recent report showed that the transient receptor potential vanilloid 1 channel agonist capsaicin allows a hydrophilic quaternary ammonium derivative of lidocaine, QX-314, to selectively block C fibers without motor block. The authors tested whether a similar differential block would be produced using amphipathicN-methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, either alone or together with 0.05% capsaicin, in a rat sciatic nerve block model. Methods Rats (n = 8/group) were anesthetized with sevoflurane, and 0.2 ml of drug was injected either alone or with capsaicin (simultaneously or 10 min later) next to the sciatic nerve in the sciatic notch. Motor function was assessed by the extensor postural thrust. Nociception was evaluated by the nocifensive withdrawal reflex and vocalization evoked by pinch of a skin fold over the lateral metatarsus (cutaneous pain) with a serrated forceps. Results N-Methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, followed by injection of capsaicin 10 min later, each elicited a predominantly nociceptive-specific blockade. In comparison, simultaneous application of each local anesthetic with capsaicin did not elicit a clinically significant differential block, with the exception of N-methyl amitriptyline. Conclusions Both tertiary amine local anesthetics and their quaternary ammonium derivatives can elicit a predominantly sensory/nociceptor selective block when followed by injection of capsaicin. The combined application of transient receptor potential vanilloid 1 channel agonists and various local anesthetics or their quaternary ammonium derivatives is an appealing strategy to achieve a long-lasting differential block in regional analgesia. PMID:18946300
Changes induced by peripheral nerve injury in the morphology and nanomechanics of sensory neurons
NASA Astrophysics Data System (ADS)
Benzina, Ouafa; Szabo, Vivien; Lucas, Olivier; Saab, Marie-belle; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla; Martin, Marta
Peripheral nerve injury in vivo promotes a regenerative growth in vitro characterized by an improved neurite regrowth. Knowledge of the conditioning injury effects on both morphology and mechanical properties of live sensory neurons could be instrumental to understand the cellular and molecular mechanisms leading to this regenerative growth. In the present study, we use differential interference contrast microscopy, fluorescence microscopy and atomic force microscopy (AFM) to show that conditioned axotomy, induced by sciatic nerve injury, does not increase somatic size of sensory neurons from adult mice lumbar dorsal root ganglia but promotes the appearance of longer and larger neurites and growth cones. AFM on live neurons is also employed to investigate changes in morphology and membrane mechanical properties of somas of conditioned neurons following sciatic nerve injury. Mechanical analysis of the soma allows distinguishing neurons having a regenerative growth from control ones, although they show similar shapes and sizes.
Identification of the sensory nerve fiber responsible for lysophosphatidic acid-induced allodynia in mice.
Ohsawa, M; Miyabe, Y; Katsu, H; Yamamoto, S; Ono, H
Lysophosphatidic acid (LPA) has been considered one of the molecular culprits for neuropathic pain. Understanding how LPA changes the function of primary afferent fibers might be an essential step for clarifying the pathogenesis of neuropathic pain. The present study was designed to identify the primary afferent fibers (A?, A?, or C) participating in LPA-induced allodynia in ddY mice. Mechanical allodynia and thermal hyperalgesia were evaluated by the von Frey filament test and thermal paw withdrawal test, respectively. Sensory nerve fiber responsiveness was measured using a Neurometer. Daily repeated intrathecal treatment with LPA led to a decrease in the mechanical, but not thermal nociceptive threshold, and a reduction in the threshold for paw withdrawal induced by 2000-Hz (A? fiber) and 250-Hz (A? fiber), but not 5-Hz (C fiber) sine-wave electrical stimulation. When the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor agonist resiniferatoxin (RTX) was administered subcutaneously before the start of LPA treatment, LPA-induced mechanical allodynia and A? and A? fiber hypersensitivity demonstrated by neurometry were not affected, indicating that TRPV1-expressing nerve fibers (possibly C fibers) might not be essential for LPA-induced allodynia. LPA-induced allodynia was reversed by treatment with RTX at 7 days after the start of LPA treatment. Expression of TRPV1 on myelinated nerve fibers after repeated intrathecal LPA treatment was observed in the dorsal root ganglion. These results suggest that sensitization of A? and A? fibers, but not C fibers, contributes to the development of intrathecally administered LPA-induced mechanical allodynia. Moreover, increased or newly expressed TRPV1 receptors in A? and A? fibers are considered to be involved in the maintenance of LPA-induced allodynia. PMID:23685168
Precision pinch performance in patients with sensory deficits of the median nerve at the carpal tunnel.
Yen, Wei-Jang; Kuo, Yao-Lung; Kuo, Li-Chieh; Chen, Shu-Min; Kuan, Ta-Shen; Hsu, Hsiu-Yun
To investigate how sensory symptoms impact the motor control of hands, in this study we examined the differences in conventional sensibility assessments and pinch force control in the pinch-holding-up activity (PHUA) test between carpal tunnel syndrome (CTS) patients and healthy controls. CTS patients (n = 82) with 122 affected hands and an equal number of control subjects were recruited to participate in the threshold, discrimination, and PHUA tests. The patients showed significantly poorer hand sensibility and lower efficiency of force adjustment in the PHUA test as compared with the control subjects. Baseline pinch strength and the percentage of maximal pinch strength for the PHUA were significantly higher for the subgroup of sensory nerve action potential (SNAP) of <16 ?V than for the subgroup of SNAP of ?16 ?V. Using a PHUA perspective to analyze the efficiency of force-adjustment could assist the clinical detection of sensory nerve dysfunction. PMID:24496877
Phenotyping sensory nerve endings in vitro in the mouse
Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W
This protocol details methods to identify and record from cutaneous primary afferent axons in an isolated mammalian skin–saphenous nerve preparation. The method is based on extracellular recordings of propagated action potentials from single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities to various stimulus modalities that are quantified by adequate and controlled stimulation of the superfused skin with heat, cold, touch, constant punctate pressure or chemicals. Responses recorded from single-fibers are comparable with those obtained in previous in vivo experiments on the same species. We describe the components and the setting-up of the basic equipment of a skin–nerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (15–45 min) and the isolation and recording of neurons (approximately 1–3 h per recording). In addition, stimulation techniques, protocols to achieve single-fiber recordings, issues of data acquisition and action potential discrimination are discussed in detail. PMID:19180088
Peripheral nerve functions may deteriorate parallel to the progression of microangiopathy in diabetic patients.
Ogawa, Kenichi; Sasaki, Hideyuki; Yamasaki, Hiroshi; Okamoto, Kunihisa; Matsuno, Shohei; Shono, Takeshi; Doi, Takuya; Arimoto, Keiko; Furuta, Hiroto; Nishi, Masahiro; Nakao, Taisei; Nanjo, Kishio
Our aim was to obtain information to help in the early detection of impaired nerve function and to assess the severity of diabetic symmetric polyneuropathy (DPN). Various somatic and autonomic nerve functions in 40 diabetics and 20 age-matched healthy volunteers were evaluated using six objective examinations: nerve conduction study, quantitative vibratory perception threshold, heart rate variability, Valsalva test, head-up tilt and quantitative sudomotor axonal reflex test (QSART). The diabetics were divided into three groups according to the severity of their microangiopathy. The nerve function data and level of impairment were compared between a healthy control and three diabetic groups. The relationships between nerve function data and clinical background were also examined using multivariate analysis. Results were as follows: (1) all nerve dysfunctions seemed to develop parallel to the progression of microangiopathy, (2) reduced nerve conduction velocity and elevated vibratory perception thresholds in the feet might be early detectable signs of DPN, (3) vasomotor and sudomotor sympathetic functions and cardiovagal functions seemed to deteriorate with the appearance of microangiopathy, (4) lowered compound muscle action potential seemed to appear at the advanced microangiopathic condition, (5) hypohydrosis was closely related to diabetic foot ulcers. In conclusion, nerve dysfunction in diabetics might generally progress with microangiopathy from somatic sensory nerve dysfunction to autonomic nerve dysfunction and then to somatic motor nerve dysfunction. Sympathetic sudomotor dysfunction might be a sensitive predictor of diabetic foot ulcer. PMID:16829339
Functional Restoration Of Precision Grip Using Slip Information Obtained From Peripheral Nerve Recordings
J. A. Hoffer; M. Haugland; T. Sinkjaer
We have implemented, in an experimental animal model, an approach for 'closed-loop' control of functional electrical stimulation (FES) of paralyzed muscles, in which tactile sensory information is recorded by implanted nerve cuff electrodes and fed back to the controller. This appmach may be applicable for functional restoration of motor function of upper or lower libs in quadriplegia, paraplegia or hemiplegia
Low-level laser treatment improves longstanding sensory aberrations in the inferior alveolar nerve following surgical trauma
NASA Astrophysics Data System (ADS)
Khullar, Shelley M.; Brodin, P.; Barkvoll, P.; Haanoes, H. R.
The incidence of inferior alveolar nerve (IAN) damage following removal of 3rd molar teeth or saggital split osteotomy has been reported as high as up to 5.5% and 100% respectively. Sensory aberrations in the IAN persisting for longer than 6 months leave some degree of permanent defect. Low level laser treatment (LLL) has a reported beneficial effect on regeneration of traumatically injured nerves. The purpose of this double blind clinical trial was to examine the effects of LLL using a GaAlAs laser (820 nm, Ronvig, Denmark) on touch and temperature sensory perception following a longstanding post surgical IAN injury. Thirteen patients were divided into two groups, one of which received real LLL (4 by 6 J per treatment along the distribution of the IAN to a total of 20 treatments during a time period between 36 - 69 days) and the other equivalent placebo LLL. The degree of mechanoreceptor injury as assessed by Semmes Weinstein Monofilaments (North Coast Medical, USA) were comparable in the two groups prior to treatment (p equals 0.9). Subsequent to LLL the real laser treatment group showed a significant improvement in mechanoreceptor sensory testing (p equals 0.01) as manifested by a decrease in load threshold (g) necessary to elicit a response from the most damaged area. The placebo LLL group showed no significant improvement, In addition, the real LLL group reported a subjective improvement in sensory function too. The degree of thermal sensitivity disability as assessed using a thermotester (Philips, Sweden) was comparable between the two groups prior to LLL p equals 0.5). However, there was no significant improvement in thermal sensitivity post LLL for either the real or placebo laser treated groups. In conclusion, GaAlAs LLL can improve mechanoreceptor perception in longstanding sensory aberration in the IAN.
Modelled temperature-dependent excitability behaviour of a generalised human peripheral sensory nerve fibre.
Smit, Jacoba E; Hanekom, Tania; Hanekom, Johan J
The objective of this study was to determine if a recently developed human Ranvier node model, which is based on a modified version of the Hodgkin-Huxley model, could predict the excitability behaviour in human peripheral sensory nerve fibres with diameters ranging from 5.0 to 15.0 microm. The Ranvier node model was extended to include a persistent sodium current and was incorporated into a generalised single cable nerve fibre model. Parameter temperature dependence was included. All calculations were performed in Matlab. Sensory nerve fibre excitability behaviour characteristics predicted by the new nerve fibre model at different temperatures and fibre diameters compared well with measured data. Absolute refractory periods deviated from measured data, while relative refractory periods were similar to measured data. Conduction velocities showed both fibre diameter and temperature dependence and were underestimated in fibres thinner than 12.5 microm. Calculated strength-duration time constants ranged from 128.5 to 183.0 micros at 37 degrees C over the studied nerve fibre diameter range, with chronaxie times about 30% shorter than strength-duration time constants. Chronaxie times exhibited temperature dependence, with values overestimated by a factor 5 at temperatures lower than body temperature. Possible explanations include the deviated absolute refractory period trend and inclusion of a nodal strangulation relationship. PMID:19579032
Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases
Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin
Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy. PMID:25221597
Cough Sensors. III. Opioid and Cannabinoid Receptors on Vagal Sensory Nerves
M. G. Belvisi; D. J. Hele
Cough is a persistent symptom of many inflammatory airways' diseases. Cough is mediated by receptors sited on sensory nerves\\u000a and then through vagal afferent pathways, which terminate in the brainstem respiratory centre. Cough is often described as\\u000a an unmet clinical need. Opioids are the only prescription-based anti-tussives currently available in the UK. They possess\\u000a limited efficacy and exhibit serious unwanted
Effects of ozone on epithelium and sensory nerves in the bronchial mucosa of healthy humans.
Krishna, M T; Springall, D; Meng, Q H; Withers, N; Macleod, D; Biscione, G; Frew, A; Polak, J; Holgate, S
Neuropeptides released from sensory nerves during inflammation have potent effects on bronchomotor tone, airway secretion, and inflammatory cells. We investigated the effects of ozone on sensory nerves by exposing 12 healthy, nonsmoking subjects to 0.2 ppm ozone and filtered air (FA) for 2 h on separate occasions, with intermittent exercise and rest. Spirometry was performed at baseline and 15 min after exposures, and bronchoscopy (bronchial biopsy and bronchoalveolar lavage [BAL]) was done 6 h after exposure. Frozen sections were immunostained for the anatomic neural marker protein gene peptide (PGP) 9.5 and the sensory neutropeptides substance P (SP) and calcitonin-gene-related peptide (CGRP). Nerves in the submucosa were quantified by image analysis. A trend toward an increase in the levels of polymorphonuclear leukocytes (PMNs) (air versus ozone, median [interquartile range]: 3.5 [2 to 5.3%] versus 9.8 [4.2 to 16.3%], p = 0.07) and ciliated epithelial cells (median [interquartile range]: 1.6 [1.3 to 3.4%] versus 5 [2.2 to 9.8%], p = 0.05) was observed in the BAL fluid (BALF). There was a significant decrease in SP immunoreactivity following ozone exposure (median [interquartile range]: 0.6 [0.05 to 1.2] versus 0.15 [0.08 to 0.18], p < 0.05). A significant inverse correlation was observed between SP immunoreactivity and: (1) percent PMNs and ciliated epithelial cells in the BALF; and (2) percent change in FEV1 following exposure to ozone. These findings indicate that short-term exposure to 0.2 ppm ozone causes epithelial shedding and stimulates subepithelial sensory nerves to release SP into the airways. The release of SP could contribute to bronchoconstriction and subsequent neutrophil infiltration into the airways. PMID:9310018
Electrical stimulation of sensory nerves with skin electrodes for research, diagnosis, communication and behavioral conditioning: A survey
ERICH A. PFEIFFERt
When electrical current is passed through the body by means of electrodes applied to the skin, sensory nerves can be stimulated.\\u000a This results in sensations that vary from barely perceivable to highly unpleasant. Such electrocutaneous stimulation of sensory\\u000a nerves has been studied by engineers, neurologists, physiologists and psychologists, who have investigated the interrelationship\\u000a between the physical parameters of the electrical
Detoxification of Organophosphate Nerve Agents by Immobilized Dual Functional
Chen, Wilfred
Detoxification of Organophosphate Nerve Agents by Immobilized Dual Functional Biocatalysts of organophosphate nerve agents in bulk liquid phase. ß 2005 Wiley Periodicals, Inc. Keywords: pesticides; degradation; OPH; CBD; hollow fiber bioreactor; immobilized cells INTRODUCTION All nerve agents belong
Michael C.-K. Wu; Stephen V. David; Jack L. Gallant
System identification is a growing approach to sensory neurophys- iology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowl- edge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This pre- diction paradigm provides an
On the identification of sensory information from mixed nerves by using single-channel cuff electrodes
Background Several groups have shown that the performance of motor neuroprostheses can be significantly improved by detecting specific sensory events related to the ongoing motor task (e.g., the slippage of an object during grasping). Algorithms have been developed to achieve this goal by processing electroneurographic (ENG) afferent signals recorded by using single-channel cuff electrodes. However, no efforts have been made so far to understand the number and type of detectable sensory events that can be differentiated from whole nerve recordings using this approach. Methods To this aim, ENG afferent signals, evoked by different sensory stimuli were recorded using single-channel cuff electrodes placed around the sciatic nerve of anesthetized rats. The ENG signals were digitally processed and several features were extracted and used as inputs for the classification. The work was performed on integral datasets, without eliminating any noisy parts, in order to be as close as possible to real application. Results The results obtained showed that single-channel cuff electrodes are able to provide information on two to three different afferent (proprioceptive, mechanical and nociceptive) stimuli, with reasonably good discrimination ability. The classification performances are affected by the SNR of the signal, which in turn is related to the diameter of the fibers encoding a particular type of neurophysiological stimulus. Conclusions Our findings indicate that signals of acceptable SNR and corresponding to different physiological modalities (e.g. mediated by different types of nerve fibers) may be distinguished. PMID:20423488
Hyperglycemia- and neuropathy-induced changes in mitochondria within sensory nerves
Hamid, Hussein S; Mervak, Colin M; Münch, Alexandra E; Robell, Nicholas J; Hayes, John M; Porzio, Michael T; Singleton, J Robinson; Smith, A Gordon; Feldman, Eva L; Lentz, Stephen I
Objective This study focused on altered mitochondrial dynamics as a potential mechanism for diabetic peripheral neuropathy (DPN). We employed both an in vitro sensory neuron model and an in situ analysis of human intraepidermal nerve fibers (IENFs) from cutaneous biopsies to measure alterations in the size distribution of mitochondria as a result of hyperglycemia and diabetes, respectively. Methods Neurite- and nerve-specific mitochondrial signals within cultured rodent sensory neurons and human IENFs were measured by employing a three-dimensional visualization and quantification technique. Skin biopsies from distal thigh (DT) and distal leg (DL) were analyzed from three groups of patients; patients with diabetes and no DPN, patients with diabetes and confirmed DPN, and healthy controls. Results This analysis demonstrated an increase in mitochondria distributed within the neurites of cultured sensory neurons exposed to hyperglycemic conditions. Similar changes were observed within IENFs of the DT in DPN patients compared to controls. This change was represented by a significant shift in the size frequency distribution of mitochondria toward larger mitochondria volumes within DT nerves of DPN patients. There was a length-dependent difference in mitochondria within IENFs. Distal leg IENFs from control patients had a significant shift toward larger volumes of mitochondrial signal compared to DT IENFs. Interpretation The results of this study support the hypothesis that altered mitochondrial dynamics may contribute to DPN pathogenesis. Future studies will examine the potential mechanisms that are responsible for mitochondrial changes within IENFs and its effect on DPN pathogenesis. PMID:25493271
Effects of Acute Organophosphorus Poisoning on Function of Peripheral Nerves: A Cohort Study
Jayasinghe, Sudheera S.; Pathirana, Kithsiri D.; Buckley, Nick A.
Background Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. The aim of this study was to measure peripheral nerve function after acute exposure to OP. Methods A cohort study was conducted with age, gender and occupation matched controls. Motor nerve conduction velocity (MNCV), amplitude and area of compound muscle action potential (CMAP), sensory nerve conduction velocity (SNCV), F- waves and electromyography (EMG) on the deltoid and the first dorsal interosseous muscles on the dominant side were performed, following acute OP poisoning. All neurophysiological assessments except EMG were performed on the controls. Assessments were performed on the day of discharge from the hospital (the first assessment) and six weeks (the second assessment) after the exposure. The controls were assessed only once. Results There were 70 patients (50 males) and 70 controls. Fifty-three patients attended for the second assessment. In the first assessment MNCV of all the motor nerves examined, CMAP amplitude and SNCV of ulnar nerve, median and ulnar F-wave occurrence in the patients were significantly reduced compared to the controls. In the second assessment significant reduction was found in SNCV of both sensory nerves examined, MNCV of ulnar nerve, CMAP amplitude of common peroneal nerve, F-wave occurrence of median and ulnar nerves. No abnormalities were detected in the patients when compared to the standard cut-off values of nerve conduction studies except F-wave occurrence. EMG studies did not show any abnormality. Conclusion There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required. PMID:23185328
Sensory Attenuation Assessed by Sensory Evoked Potentials in Functional Movement Disorders
Macerollo, Antonella; Chen, Jui-Cheng; Pareés, Isabel; Kassavetis, Panagiotis; Kilner, James Morvan; Edwards, Mark John
Background Functional (psychogenic) movement disorders (FMD) have features associated with voluntary movement (e.g. distractibility) but patients report movements to be out of their control. One explanation for this phenomenon is that sense of agency for movement is impaired. The phenomenon of reduction in the intensity of sensory experience when movement is self-generated and a reduction in sensory evoked potentials (SEPs) amplitude at the onset of self-paced movement (sensory attenuation) have been linked to sense of agency for movement. Methods We compared amplitude of SEPs from median nerve stimulation at rest and at the onset of a self-paced movement of the thumb in 17 patients with FMD and 17 healthy controls. Results Patients showed lack of attenuation of SEPs at the onset of movement compared to reduction in amplitude of SEPs in controls. FMD patients had significantly different ratios of movement onset to rest SEPs than did healthy controls at each electrode: 0.79 in healthy controls and 1.35 in patients at F3 (t = -4.22, p<0.001), 0.78 in healthy controls and 1.12 at patients C3 (t = -3.15, p = 0.004) and 0.77 in healthy controls and 1.05 at patients P3 (t = -2.88, p = 0.007). Conclusions Patients with FMD have reduced sensory attenuation as measured by SEPs at onset of self-paced movement. This finding can be plausibly linked to impairment of sense of agency for movement in these patients. PMID:26091500
Orbital pain and unruptured carotid-posterior communicating artery aneurysms: the role of sensory fibers of the third cranial nerve.
Lanzino, G; Andreoli, A; Tognetti, F; Limoni, P; Calbucci, F; Bortolami, R; Lucchi, M L; Callegari, E; Testa, C
Intact aneurysms of the carotid siphon at the point of take-off of the posterior communicating artery may exhibit orbital pain, whether associated with oculomotor palsy or not as a warning symptom prior to rupture. In order to explain this symptom the hypothesis of a sensory pathway within the third cranial nerve, which is liable to compression by the enlarging aneurysm sac, has been investigated. Data from human autopsy material show evidence of sensory ganglion cells within the rootlets of the oculomotor nerve; furthermore, studies in animals prove that the third nerve contains sensory fibers which run proximally along the nerve bundles, enter the brainstem and reach the spinal trigeminal nucleus. These fibers come from the ophthalmic division of the fifth nerve and join the third nerve at the level of the lateral wall of the cavernous sinus. Although a number of questions remain to be solved, the presence of a sensory pattern within the third nerve could account for fronto-orbital pain from enlarging aneurysms impinging on the third nerve itself. PMID:8434520
Sigma-1 receptor expression in sensory neurons and the effect of painful peripheral nerve injury
Background The sigma-1 receptor (?1R), an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion (DRG) neurons, contributing to the development of pain. The ?1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, ?1R expression in the DRG has not been studied. We therefore characterized ?1R expression in DRGs at baseline and following spinal nerve ligation (SNL) in rats. Results Immunohistochemical (IHC) studies in DRG sections show ?1R in both neuronal somata and satellite glial cells. The punctate distribution of ?1R in the neuronal cytoplasm suggests expression in the endoplasmic reticulum. When classified by neuronal size, large neurons (>1300 ?m) showed higher levels of ?1R staining than other groups (700-1300 ?m, <700 ?m). Comparing ?1R expression in neuronal groups characterized by expression of calcitonin gene-related peptide (CGRP), isolectin-B4 (IB4) and neurofilament-200 (NF-200), we found ?1R expression in all three neuronal subpopulations, with highest levels of ?1R expression in the NF-200 group. After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased ?1R protein but unaffected transcript level, compared with Control DRGs. IHC images also showed decreased ?1R protein expression, in SNL L5 DRGs, and to a lesser extent in the neighboring SNL L4 DRGs. Neurons labeled by CGRP and NF-200 showed decreased ?1R expression in L5 and, to a lesser extent, L4 DRGs. In IB4-labeled neurons, ?1R expression decreased only in axotomized L5 DRGs. Satellite cells also showed decreased ?1R expression in L5 DRGs after SNL. Conclusions Our data show that ?1R is present in both sensory neurons and satellite cells in rat DRGs. Expression of ?1R is down-regulated in axotomized neurons as well as in their accompanying satellite glial cells, while neighboring uninjured neurons show a lesser down-regulation. Therefore, elevated ?1R expression in neuropathic pain is not an explanation for pain relief after ?1R blockade. This implies that increased levels of endogenous ?1R agonists may play a role, and diminished neuroprotection from loss of glial ?1R may be a contributing factor. PMID:24015960
A comparison of nerve conduction velocities and current perception thresholds as correlates of clinical severity of diabetic sensory neuropathy
M S Rendell; J J Katims; R Richter; F Rowland
Nerve conduction velocities (NCVs) are the standard measurements used to confirm the presence or absence of diabetic neuropathy. NCVs were contrasted with the newer technique of measurement of alternating current perception thresholds (CPTs) in assessing the quantitative level of correlation with severity of diabetic sensory neuropathy. A very detailed, scored neurological history (symptoms) and physical examination, emphasising sensory assessment, was
Serial changes of sensory nerve conduction velocity and minimal F-wave latency in streptozotocin-induced diabetic rats
Noriaki Kato; Mitsuhiro Makino; Kuniharu Mizuno; Tsunemasa Suzuki; Masaomi Shindo
We studied the serial changes of sensory nerve conduction velocity (SNCV) in the caudal nerve of streptozotocin (STZ)-induced diabetic rats using a new technical method. Minimal F-wave latency was also studied by stimulating the tibial nerve. The SNCV in the diabetic rats was slower than that in the normal rats 2 weeks after STZ injection, and minimal F-wave latency was
Overexpression of Nerve Growth Factor in Skin Selectively Affects the Survival and Functional Properties of Nociceptors
C. L. Stucky; M. Koltzenburg; M. Schneider; M. G. Engle; K. M. Albers; B. M. Davis
Mice that overexpress nerve growth factor (NGF-OE) in the skin have double the normal number of cutaneous sensory neurons, have increased innervation of the skin and spinal cord, and are hyperalgesic. Here, we have asked whether the increased cu- taneous NGF level results in a selective survival of only certain functional types of neurons and whether it changes the prop-
Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice
Introduction Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sprouting; however, neuroplasticity is generally thought to be greater in young versus old nerves. Here we explore whether sensory and sympathetic nerve fibers can undergo a significant ectopic nerve remodeling in the painful arthritic knee joint of geriatric mice. Methods Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic nerve fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), and growth-associated protein 43 (GAP43; nerve fibers undergoing sprouting). Results At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ nerve fibers in the synovium and periosteum. Conclusions Sensory and sympathetic nerve fibers that innervate the aged knee joint clearly maintain the capacity for robust nerve sprouting and formation of neuroma-like structures after inflammation/injury. Understanding the factors that drive this neuroplasticity, whether this pathologic reorganization of nerve fibers contributes to chronic joint pain, and how the phenotype of sensory and sympathetic nerves changes with age may provide pharmacologic insight and targets for better controlling aging-related joint pain. PMID:22548760
Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.
Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela
After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. PMID:25253866
Evaluation of the function status of the ulnar nerve in carpal tunnel syndrome.
Zhang, J; Liu, N; Wang, Y W; Zhang, Z C; Zheng, L N; Zhu, J
Many carpal tunnel syndrome (CTS) patients have symptoms in both the median and ulnar digits more frequently than in the median digits alone. This is possibly because of close anatomical contiguity of the carpal tunnel and Guyon's canal, and the high pressure may also affect the latter, causing indirect compression of ulnar nerve fibers. Thus, we evaluated the functional status of the ulnar nerve in patients with CTS in order to investigate the relationship between ulnar nerve impairment and sensory symptoms of the ulnar territory. Electrophysiological studies were conducted in CTS patients and healthy controls. CTS patients were divided into the mild/moderate group and severe group; they were further divided into the symptomatic and asymptomatic subgroups according to the sensory symptom of the fifth digit region. The findings suggest that CTS patients could have coexisting ulnar nerve wrist entrapments that might exacerbate the severity of CTS. Sensory impairment in the ulnar territory was observed more frequently in the mild/moderate stage of CTS, which is associated with ulnar nerve involvement. These findings also suggest that damage to the ulnar nerve fibers caused by compression forces in Guyon's canal may underlie the ulnar spread of symptoms in CTS. PMID:25966136
Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes' hearing problem: an innovation in multi-channel-array skin-hearing technology
Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong
The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes' hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized. PMID:25317171
Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes' hearing problem: an innovation in multi-channel-array skin-hearing technology.
Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong
The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes' hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized. PMID:25317171
Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.
Jordt, Sven-Eric; Bautista, Diana M; Chuang, Huai-Hu; McKemy, David D; Zygmunt, Peter M; Högestätt, Edward D; Meng, Ian D; Julius, David
Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds. Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust hypersensitivity to thermal and mechanical stimuli. Despite their widespread use in both the kitchen and the laboratory, the molecular mechanism through which isothiocyanates mediate their effects remains unknown. Here we show that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the TRP ion channel family recently implicated in the detection of noxious cold. These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors. PMID:14712238
Motor Nerve Transfers to Restore Extrinsic Median Nerve Function: Case Report
Hsiao, Eugene C.; Tung, Thomas H.; Mackinnon, Susan E.
Active pronation is important for many activities of daily living. Loss of median nerve function including pronation is a rare sequela of humerus fracture. Tendon transfers to restore pronation are reserved for the obstetrical brachial plexus palsy patient. Transfer of expendable motor nerves is a treatment modality that can be used to restore active pronation. Nerve transfers are advantageous in that they do not require prolonged immobilization postoperatively, avoid operating within the zone of injury, reinnervate muscles in their native location prior to degeneration of the motor end plates, and result in minimal donor deficit. We report a case of lost median nerve function after a humerus fracture. Pronation was restored with transfer of the extensor carpi radialis brevis branch of the radial nerve to the pronator teres branch of the median nerve. Anterior interosseous nerve function was restored with transfer of the supinator branch to the anterior interosseous nerve. Clinically evident motor function was seen at 4 months postoperatively and continued to improve for the following 18 months. The patient has 4+/5 pronator teres, 4+/5 flexor pollicis longus, and 4?/5 index finger flexor digitorum profundus function. The transfer of the extensor carpi radialis brevis branch of the radial nerve to the pronator teres and supinator branch of the radial nerve to the anterior interosseous nerve is a novel, previously unreported method to restore extrinsic median nerve function. PMID:18807095
Sensory fibers of the pelvic nerve innervating the Rat's urinary bladder.
Shea, V K; Cai, R; Crepps, B; Mason, J L; Perl, E R
Much attention has been given to the pelvic nerve afferent innervation of the urinary bladder; however, reports differ considerably in descriptions of afferent receptor types, their conduction velocities, and their potential roles in bladder reflexes and sensation. The present study was undertaken to do a relatively unbiased sampling of bladder afferent fibers of the pelvic nerve in adult female rats. The search stimulus for units to be studied was electrical stimulation of both the bladder nerves and the pelvic nerve. Single-unit activity of 100 L(6) dorsal root fibers, activated by both pelvic and bladder nerve stimulation, was analyzed. Sixty-five units had C-fiber and 35 units had Adelta-fiber conduction velocities. Receptive characteristics were established by direct mechanical stimulation, filling of the bladder with 0.9% NaCl at a physiological speed and by filling the bladder with solutions containing capsaicin, potassium, or turpentine oil. The majority (61) of these fibers were unambiguously excited by bladder filling with 0.9% NaCl and were classified as mechanoreceptors. All mechanoreceptors with receptive fields on the body of the bladder had low pressure thresholds (=10 mmHg). Receptive fields of units with higher thresholds were near the ureterovesical junction, on the base of the bladder or could not be found. Neither thresholds nor suprathreshold responses could be related to conduction velocity. Bladder compliance and mechanoreceptor thresholds were influenced by the stage of the estrous cycle: both were lowest in proestrous rats and highest in metaestrous rats. Mechanoreceptors innervating the body of the bladder and the region near the ureterovesical junction showed two patterns of responsiveness to slow bladder filling. One group of units exhibited increasing activity with increasing pressure up to 40 mmHg, while the other group showed a peak in activity at pressures below 40 mmHg followed by a plateau or decrease in activity with increasing pressure. It is proposed that differences in stimulus transduction relate to the different response patterns. Thirty-nine units failed to respond to bladder filling. Eight of these were excited by intravesical potassium or capsaicin and were classified as chemoreceptors. The remaining 31 units were not excited by any stimulus tested. Chemoreceptors and unexcited units had both Adelta and C afferent fibers. We conclude that the pelvic nerve sensory innervation of the rat bladder is complex, may be sensitive to hormonal status, and that the properties of individual sensory receptors are not related in an obvious manner to the conduction velocity of their fibers. PMID:11024085
Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities
NASA Technical Reports Server (NTRS)
Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.
Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.
Functional and structural nerve fiber findings in heterozygote patients with Fabry disease.
Torvin Mřller, Anette; Winther Bach, Flemming; Feldt-Rasmussen, Ulla; Rasmussen, Ase; Hasholt, Lis; Lan, He; Sommer, Claudia; Křlvraa, Steen; Ballegaard, Martin; Staehelin Jensen, Troels
Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation between pain VAS score, quantitative sensory testing and intraepidermal nerve fiber density. Our study demonstrates that careful evaluation of symptoms in female Fabry patients is important as small fiber disease manifestations are present, which in some cases is only detected by skin biopsy. PMID:19665302
Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons
Richardson, P.M.; Riopelle, R.J.
To investigate the distribution of nerve growth factor (NGF) receptors on peripheral and central axons, (/sup 125/I)NGF was injected into the sciatic nerve or spinal cord of adult rats. Accumulation of (/sup 125/I)NGF in lumbar dorsal root ganglia was monitored by gamma emission counting and radioautography. (/sup 125/I)NGF, injected endoneurially in small quantities, was taken into sensory axons by a saturable process and was transported retrogradely to their cell bodies at a maximal rate of 2.5 to 7.5 mm/hr. Because very little (/sup 125/I)NGF reached peripheral terminals, the results were interpreted to indicate that receptors for NGF are present on nonterminal segments of sensory axons. The specificity and high affinity of NGF uptake were illustrated by observations that negligible amounts of gamma activity accumulated in lumbar dorsal root ganglia after comparable intraneural injection of (/sup 125/I) cytochrome C or (/sup 125/I)oxidized NGF. Similar techniques were used to demonstrate avid internalization and retrograde transport of (/sup 125/I)NGF by intraspinal axons arising from dorsal root ganglia. Following injection of (/sup 125/I)NGF into lumbar or cervical regions of the spinal cord, neuronal perikarya were clearly labeled in radioautographs of lumbar dorsal root ganglia. Sites for NGF uptake on primary sensory neurons in the adult rat are not restricted to peripheral axon terminals but are extensively distributed along both peripheral and central axons. Receptors on axons provide a mechanism whereby NGF supplied by glia could influence neuronal maintenance or axonal regeneration.
Activation of EP4 receptors contributes to prostaglandin E2-mediated stimulation of renal sensory nerves.
Kopp, Ulla C; Cicha, Michael Z; Nakamura, Kazuhiro; Nüsing, Rolf M; Smith, Lori A; Hökfelt, Tomas
Induction of cyclooxygenase-2 (COX-2) in the renal pelvic wall increases prostaglandin E(2) (PGE(2)) leading to stimulation of cAMP production, which results in substance P (SP) release and activation of renal mechanosensory nerves. The subtype of PGE receptors involved, EP2 and/or EP4, was studied by immunohistochemistry and renal pelvic administration of agonists and antagonists of EP2 and EP4 receptors. EP4 receptor-like immunoreactivity (LI) was colocalized with calcitonin gene-related peptide (CGRP)-LI in dorsal root ganglia (DRGs) at Th(9)-L(1) and in nerve terminals in the renal pelvic wall. Th(9)-L(1) DRG neurons also contained EP3 receptor-LI and COX-2-LI, each of which was colocalized with CGRP-LI in some neurons. No renal pelvic nerves contained EP3 receptor-LI and only very few nerves COX-2-LI. The EP1/EP2 receptor antagonist AH-6809 (20 microM) had no effect on SP release produced by PGE(2) (0.14 microM) from an isolated rat renal pelvic wall preparation. However, the EP4 receptor antagonist L-161,982 (10 microM) blocked the SP release produced by the EP2/EP4 receptor agonist butaprost (10 microM) 12 +/- 2 vs. 2 +/- 1 and PGE(2), 9 +/- 1 vs. 1 +/- 0 pg/min. The SP release by butaprost and PGE(2) was similarly blocked by the EP4 receptor antagonist AH-23848 (30 microM). In anesthetized rats, the afferent renal nerve activity (ARNA) responses to butaprost 700 +/- 100 and PGE(2).780 +/- 100%.s (area under the curve of ARNA vs. time) were unaffected by renal pelvic perfusion with AH-6809. However, 1 microM L-161,982 and 10 microM AH-23848 blocked the ARNA responses to butaprost by 94 +/- 5 and 78 +/- 10%, respectively, and to PGE(2) by 74 +/- 16 and 74 +/- 11%, respectively. L-161,982 also blocked the ARNA response to increasing renal pelvic pressure 10 mmHg, 85 +/- 5%. In conclusion, PGE(2) increases renal pelvic release of SP and ARNA by activating EP4 receptors on renal sensory nerve fibers. PMID:15292051
Nerve Growth Factor-Dependence of Herpes Simplex Virus Latency in Peripheral Sympathetic and Sensory Neurons in vitro
C. L. Wilcox; L. Smith; C. R. Freed; E. M. Johnson
Previously, we reported that nerve growth factor (NGF) is required to maintain herpes simplex virus (HSV) latency in cultures of rat sympathetic neurons (Wilcox and Johnson, 1987, 1988). Here, we extend these results by showing that NGF was also required to maintain HSV latency in cultures of sensory neurons obtained from dorsal root ganglia of rats, monkeys, and humans. The
Effects of acetyl- and proprionyl- l-carnitine on peripheral nerve function and vascular supply in experimental diabetes
M. A. Cotter; N. E. Cameron; A. Keegan; K. C. Dines
l-Carnitine metabolism is abnormal in diabetes mellitus, and treatment with acetyl-l-carnitine (ALC) improves the function of cardiac muscle, retina, and peripheral nerve in experimental models. The aim was to compare the effects of ALC and proprionyl-l-carnitine (PLC) on motor and sensory nerve conduction in streptozotocin-diabetic rats and to ascertain whether their action could be mediated by a vascular mechanism. ALC
The relationship between lingual and hypoglossal nerve function and quality of life in head and neck cancer.
Elfring, T; Boliek, C A; Winget, M; Paulsen, C; Seikaly, H; Rieger, J M
Sensorimotor impairment of the tongue has the potential to affect speech and swallowing. The purpose of this study was to critically examine the effects of nerve preservation and reinnervation after reconstruction of the base of tongue on patient-perceived outcomes of quality of life (QoL) related to speech and swallowing through completion of the EORTC QLQ-H&N35 standardised questionnaire. Thirty participants with a diagnosis of base of tongue cancer underwent primary resection and reconstruction with a radial forearm free flap, which may or may not have included nerve repair to the lingual nerve, hypoglossal nerve or both. Eight QoL domains sensitive to changes in motor and sensory nerve function were included in the analysis. Transected lingual and hypoglossal nerves were associated with difficulty in swallowing, social eating, dry mouth and social contact. There were fewer problems reported when these nerves were either repaired or left intact. There were no significant differences between patient nerve status and QoL outcomes for speech, sticky saliva and use of feeding tubes. This study was the first to examine the impact of sensory or motor nerve transection and reconstruction on health-related QoL outcomes. PMID:24289234
Thyroid hormone reduces the loss of axotomized sensory neurons in dorsal root ganglia after sciatic nerve transection in adult rat.
Schenker, Michel; Kraftsik, Rudolf; Glauser, Liliane; Kuntzer, Thierry; Bogousslavsky, Julien; Barakat-Walter, Ibtissam
We have shown that a local administration of thyroid hormones (T3) at the level of transected rat sciatic nerve induced a significant increase in the number of regenerated axons. To address the question of whether local administration of T3 rescues the axotomized sensory neurons from death, in the present study we estimated the total number of surviving neurons per dorsal root ganglion (DRG) in three experimental group animals. Forty-five days following rat sciatic nerve transection, the lumbar (L4 and L5) DRG were removed from PBS-control, T3-treated as well as from unoperated rats, and serial sections (1 microm) were cut. The physical dissector method was used to estimate the total number of sensory neurons in the DRGs. Our results revealed that in PBS-control rats transection of sciatic nerve leads to a significant (P < 0.001) decrease in the mean number of sensory neurons (8743.8 +/- 748.6) compared with the number of neurons in nontransected ganglion (mean 13,293.7 +/- 1368.4). However, administration of T3 immediately after sciatic nerve transection rescues a great number of axotomized neurons so that their mean neuron number (12,045.8 +/- 929.8) is not significantly different from the mean number of neurons in the nontransected ganglion. In addition, the volume of ganglia showed a similar tendency. These results suggest that T3 rescues a high number of axotomized sensory neurons from death and allows these cells to grow new axons. We believe that the relative preservation of neurons is important in considering future therapeutic approaches of human peripheral nerve lesion and sensory neuropathy. PMID:14637094
VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity
Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain. PMID:23249422
How does morphology relate to function in sensory arbors?
Hall, David H.; Treinin, Millet
Sensory dendrites fall into many different morphological and functional classes. Polymodal nociceptors are one subclass of sensory neurons, which are of particular note due to their elaborate dendritic arbors. Complex developmental programs are required to form these arbors, and there is striking conservation of morphology, function, and molecular determinants between vertebrate and invertebrate polymodal nociceptors. Based on these studies, we argue that arbor morphology plays an important role in the function of polymodal nociceptors. Similar associations between form and function may explain the plethora of dendrite morphologies seen among all sensory neurons. PMID:21840610
Autologous Fat Grafting Improves Facial Nerve Function
Klinger, Marco; Lisa, Andrea; Caviggioli, Fabio; Maione, Luca; Murolo, Matteo; Vinci, Valeriano; Klinger, Francesco Maria
We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman's technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function.
Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson's Disease Patients.
Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H; Caviness, John N; Shill, Holly A; Sabbagh, Marwan; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G
Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated ?-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia. PMID:26041249
Sensory recovery of innervated and non-innervated radial forearm free flaps: functional implications.
Netscher, D; Armenta, A H; Meade, R A; Alford, E L
Findings reported in the literature on the sensation provided by intraorally applied innervated vs. non-innervated radial forearm free flaps differ. In an effort to understand these differences in sensory recovery, the authors carried out sensory evaluations in 12 patients who had undergone radial forearm free flaps. Seven patients had innervated flaps for defects of the tongue and floor of mouth; five had non-innervated flaps to various sites. Flap sensitivity to temperature, light touch, dull touch, and sharpness and two-point discrimination was assessed at the donor site and contralaterally, and at the recipient site and contralateral mirror-image oral mucosa. Patients subjectively rated post-reconstruction sensation and provided quality of life (QOOL) data. The innervated flaps demonstrated better sensory recovery than the non-innervated flaps, although the latter did restore reasonable sensation. This paper describes the results, compares the study to other similar studies, and discusses various factors in the sensory recovery of both innervated and non-innervated intraoral radial forearm free flaps. The authors conclude that, although the trend in this study is toward improved function with the innervated flaps, these flaps do not appear to offer major intraoral functional advantage over the non-innervated flaps, which attain reasonably effective sensory recovery from neural ingrowth, if the lingual nerve is intact. PMID:10803620
Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function
Viader, Andreu; Golden, Judith P.; Baloh, Robert H.; Schmidt, Robert E.; Hunter, Daniel A.; Milbrandt, Jeffrey
Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable but, as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies. PMID:21752989
Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress.
Kwiecien, S; Konturek, P C; Sliwowski, Z; Mitis-Musiol, M; Pawlik, M W; Brzozowski, B; Jasnos, K; Magierowski, M; Konturek, S J; Brzozowski, T
Gastric microcirculation plays an important role in the maintenance of the mucosal gastric integrity and the mechanism of injury as well as providing protection to the gastric mucosa. Disturbances in the blood perfusion, through the microcapillaries within the gastric mucosa may result in the formation of mucosal damage. Acute gastric mucosal lesions constitute an important clinical problem. Originally, one of the essential component of maintaining the gastric mucosal integrity was the biosynthesis of prostaglandins (PGs), an issue that has captured the attention of numerous investigations. PGs form due to the activity of cyclooxygenase (COX), an enzyme which is divided into 2 isoforms: constitutive (COX-1) and inducible (COX-2) ones. The inhibition of COX-1 by SC-560, or COX-2 by rofecoxib, reduces gastric blood flow (GBF) and impairs gastric mucosal integrity. Another detrimental effect on the gastric mucosal barrier results from the ablation of sensory afferent nerves by neurotoxic doses of capsaicin. Functional ablation of the sensory afferent nerves by capsaicin attenuates GBF and also renders the gastric mucosa more susceptible to gastric mucosal damage induced by ethanol, aspirin and stress. However, the role of reactive oxygen species (ROS) in the interaction between COX specific inhibitors and afferent sensory nerves has not been extensively studied. The aim of our present study was to determine the participation of ROS in pathogenesis of stress-induced gastric lesions in rats administered with SC-560 or rofecoxib, with or without ablation of the sensory afferent nerves. ROS were estimated by measuring the gastric mucosal tissue level of MDA and 4-HNE, the products of lipid peroxidation by ROS as well as the SOD activity and reduced glutathione (GSH) levels, both considered to be scavengers of ROS. It was demonstrated that exposure to 3.5 h of WRS resulted in gastric lesions, causing a significant increase of MDA and 4-HNE in the gastric mucosa, accompanied by a decrease of SOD activity and mucosal GSH level. Pretreatment with COX-1 and COX-2 inhibitors (SC-560 and rofecoxib, respectively) aggravated the number of gastric lesions, decreased GBF, attenuated GSH level without further significant changes in MDA and 4-HNE tissue levels and SOD activity. Furthermore, the capsaicin--nactivation of sensory nerves resulted in exaggeration of gastric mucosal damage induced by WRS and this was further augmented by rofecoxib. We conclude that oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity and the fall in GSH tissue level, may play an important role in the mechanism of interaction between the inhibition of COX activity and afferent sensory nerves releasing vasoactive neuropeptides. This is supported by the fact that the addition of specific COX-1 or COX-2 inhibitors to animals with capsaicin denervation led to exacerbation of gastric lesions, and further fall in the antioxidizing status of gastric mucosa exposed to stress. PMID:22653901
Edaravone promotes functional recovery after mechanical peripheral nerve injury
Zhang, Teng; Li, Zhengwei; Dong, Jianli; Nan, Feng; Li, Tao; Yu, Qing
Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expression was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechanical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression. PMID:25374594
Peripheral nerve lengthening as a regenerative strategy
Vaz, Kenneth M.; Brown, Justin M.; Shah, Sameer B.
Peripheral nerve injury impairs motor, sensory, and autonomic function, incurring substantial financial costs and diminished quality of life. For large nerve gaps, proximal lesions, or chronic nerve injury, the prognosis for recovery is particularly poor, even with autografts, the current gold standard for treating small to moderate nerve gaps. In vivo elongation of intact proximal stumps towards the injured distal stumps of severed peripheral nerves may offer a promising new strategy to treat nerve injury. This review describes several nerve lengthening strategies, including a novel internal fixator device that enables rapid and distal reconnection of proximal and distal nerve stumps. PMID:25317163
Exploring developmental, functional, and evolutionary aspects of amphioxus sensory cells
Satoh, Gouki
Amphioxus has neither elaborated brains nor definitive sensory organs, so that the two may have evolved in a mutually affecting manner and given rise to the forms seen in extant vertebrates. Clarifying the developmental and functional aspects of the amphioxus sensory system is thus pivotal for inferring the early evolution of vertebrates. Morphological studies have identified and classified amphioxus sensory cells; however, it is completely unknown whether the morphological classification makes sense in functional and evolutionary terms. Molecular markers, such as gene expression, are therefore indispensable for investigating the developmental and functional aspects of amphioxus sensory cells. This article reviews recent molecular studies on amphioxus sensory cells. Increasing evidence shows that the non-neural ectoderm of amphioxus can be subdivided into molecularly distinct subdomains by the combinatorial code of developmental cues involving the RA-dependent Hox code, suggesting that amphioxus epithelial sensory cells developed along positional information. This study focuses particularly on research involving the molecular phylogeny and expression of the seven-transmembrane, G protein-coupled receptor (GPCR) genes and discusses the usefulness of this information for characterizing the sensory cells of amphioxus. PMID:16763674
Glycomimetic functionalized collagen hydrogels for peripheral nerve repair
NASA Astrophysics Data System (ADS)
Masand, Shirley Narain
Despite the innate regenerative potential of the peripheral nervous system, functional recovery is often limited. The goal of this dissertation was to develop a clinically relevant biomaterial strategy to (1) encourage the regrowth of axons and (2) direct them down their appropriate motor tracts. To this end, we use peptide mimics of two glycans, polysialic acid (PSA) and an epitope first discovered on human natural killer cells (HNK-1), to functionalize type I collagen hydrogels. Previous studies have shown that these molecules, in their glycan and glycomimetic form, are associated with acceleration of neurite outgrowth, glial cell proliferation, and motoneuron targeting. In vitro, we demonstrated the retained functionality of the peptide glycomimetics after conjugation to a type I collagen backbone. While HNK-functionalized collagen increased motor neurite outgrowth, PSA-functionalized collagen encouraged motor and sensory neurite outgrowth and Schwann cell extension and proliferation. When we introduce these glycomimetic-functionalized collagen hydrogels into a critical gap femoral nerve model, we show that both PSA and HNK-functionalized hydrogels yielded a significant increase in functional recovery when compared to saline, native and scramble-coupled hydrogels. However, there was an interesting divergence in the morphological results: PSA-functionalized hydrogels increased axon count and HNK-functionalized hydrogels increased motoneuron targeting and myelination. We believed that these differences may be attributed to distinct mechanisms by which the glycomimetics impart their benefit. Interestingly, however, we found no synergistic gain in recovery with the use of our composite hydrogels which we speculated may be due to an inadequate dose of the individual glycomimetic. To address this possibility, we show that increasing the amount of functionalized peptide functionalized in our composite hydrogels led to increases in axon count and area of regeneration, but does not affect the degree of functional recovery. Finally, in order to assess potential mechanisms by which our glycomimetics impart benefit, we describe a novel platform for studying neural cell/biomaterial interaction through the use of two types of motoneuron cultures, dissociated spinal cord neurons and organotypic spinal cord slices. We show promising evidence that this strategy can be used to probe signaling pathways potentially involved in the action of these bioactives.
Aging and the Interaction of Sensory Cortical Function and Structure
Peiffer, Ann M.; Hugenschmidt, Christina E.; Maldjian, Joseph A.; Casanova, Ramon; Srikanth, Ryali; Hayasaka, Satoru; Burdette, Jonathan H.; Kraft, Robert A.; Laurienti, Paul J.
Even the healthiest older adults experience changes in cognitive and sensory function. Studies show that older adults have reduced neural responses to sensory information. However, it is well known that sensory systems do not act in isolation but function cooperatively to either enhance or suppress neural responses to individual environmental stimuli. Very little research has been dedicated to understanding how aging affects the interactions between sensory systems, especially cross-modal deactivations or the ability of one sensory system (e.g., audition) to suppress the neural responses in another sensory system cortex (e.g., vision). Such cross-modal interactions have been implicated in attentional shifts between sensory modalities and could account for increased distractibility in older adults. To assess age-related changes in cross-modal deactivations, functional MRI studies were performed in 61 adults between 18 and 80 years old during simple auditory and visual discrimination tasks. Results within visual cortex confirmed previous findings of decreased responses to visual stimuli for older adults. Age-related changes in the visual cortical response to auditory stimuli were, however, much more complex and suggested an alteration with age in the functional interactions between the senses. Ventral visual cortical regions exhibited cross-modal deactivations in younger but not older adults, whereas more dorsal aspects of visual cortex were suppressed in older but not younger adults. These differences in deactivation also remained after adjusting for age-related reductions in brain volume of sensory cortex. Thus, functional differences in cortical activity between older and younger adults cannot solely be accounted for by differences in gray matter volume. PMID:18072271
Sensory and Cognitive Factors Influencing Functional Ability in Older Adults
Kimberly M. Wood; Jerri D. Edwards; Olivio J. Clay; Virginia G. Wadley; Daniel L. Roenker; Karlene K. Ball
Background: Age-related sensory and cognitive impairments have been related to functional performance in older adults. With regard to cognitive abilities, processing speed in particular may be strongly related to older adults' abilities to perform everyday tasks. Identifying and comparing cognitive correlates of functional performance is particularly important in order to design interventions to promote independence and prevent functional disability. Objective:
Effect of Remote Sensory Noise on Hand Function Post Stroke
Seo, Na Jin; Kosmopoulos, Marcella Lyn; Enders, Leah R.; Hur, Pilwon
Hand motor impairment persists after stroke. Sensory inputs may facilitate recovery of motor function. This pilot study tested the effectiveness of tactile sensory noise in improving hand motor function in chronic stroke survivors with tactile sensory deficits, using a repeated measures design. Sensory noise in the form of subthreshold, white noise, mechanical vibration was applied to the wrist skin during motor tasks. Hand dexterity assessed by the Nine Hole Peg Test and the Box and Block Test and pinch strength significantly improved when the sensory noise was turned on compared with when it was turned off in chronic stroke survivors. The subthreshold sensory noise to the wrist appears to induce improvements in hand motor function possibly via neuronal connections in the sensoriomotor cortex. The approach of applying concomitant, unperceivable mechanical vibration to the wrist during hand motor tasks is easily adoptable for clinic use as well as unsupervised home use. This pilot study suggests a potential for a wristband-type assistive device to complement hand rehabilitation for stroke survivors with sensorimotor deficit. PMID:25477806
Nerve function in workers with long term exposure to trichloroethene.
Ruijten, M W; Verberk, M M; Sallé, H J
Certain functions of the nervous system were examined in 31 printing workers (mean age 44) exposed to trichloroethene (mean duration 16 years) and 28 controls (mean age 45). In the sural nerve the conduction velocity (SNCV), response amplitude, and refractory period (SRP) were measured. The latencies of the masseter and the blink reflex were determined to test the trigeminal nerve. In the peroneal nerve the conduction velocity of fast and slow nerve fibres, the response amplitude, and the refractory period were determined. As a measure of autonomic nerve function the response of the heart rate was determined to isometric muscle contraction and deep breathing. Individual cumulative exposure was calculated on the basis of exposure levels in the past. The mean cumulative exposure of the exposed workers was 704 ppm x years. For the assessment of the exposure effect relation a multiple linear regression model was used. A slight reduction (-1.1 m/s) in the SNCV was found and a prolongation (0.4 ms) of the SRP (mean of the controls 1.95 ms). The latency of the masseter reflex (mean 10.4 ms) had increased (0.4 ms). With respect to the blink reflex no prolongation was found. No impairment was found in the functions of motor and autonomic nerves. This study shows that the refractory period may be a sensitive indicator of preclinical toxic neuropathies. Long term exposure to trichloroethene at threshold limit values (about 35 ppm) may slightly affect the trigeminal and sural nerves. PMID:1998613
Enhanced early sensory outcome after nerve repair as a result of immediate post-operative re-learning: a randomized controlled trial.
Rosén, B; Vikström, P; Turner, S; McGrouther, D A; Selles, R W; Schreuders, T A R; Björkman, A
We assessed the use of guided plasticity training to improve the outcome in the first 6 months after nerve repair. In a multicentre randomized controlled trial, 37 adults with median or ulnar nerve repair at the distal forearm were randomized to intervention, starting the first week after surgery with sensory and motor re-learning using mirror visual feedback and observation of touch, or to a control group with re-learning starting when reinnervation could be detected. The primary outcome at 3 and 6 months post-operatively was discriminative touch (shape texture identification test, part of the Rosen score). At 6 months, discriminative touch was significantly better in the early intervention group. Improvement of discriminative touch between 3 and 6 months was also significantly greater in that group. There were no significant differences in motor function, pain or in the total score. We conclude that early re-learning using guided plasticity may have a potential to improve the outcomes after nerve repair. LEVEL OF EVIDENCE II. PMID:25294735
Motor and sensory nerve conduction velocity in the baboon: normal values and changes during acrylamide neuropathy
A. P. Hopkins; R. W. Gilliatt
Nerve conduction velocity and the amplitude of nerve and muscle action potentials have been measured in the median and anterior tibial nerves of normal adult and infant baboons. The effect of altered temperature on velocity has also been investigated. Seven adult baboons were intoxicated with acrylamide. In animals given 10-15 mg\\/kg\\/day, the gradual development of a peripheral neuropathy was accompanied
From the Cover: Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration
Alka A. Vyas; Himatkumar V. Patel; Susan E. Fromholt; Marija Heffer-Lauc; Kavita A. Vyas; Jiyoung Dang; Melitta Schachner; Ronald L. Schnaar
Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition
Peripheral nerve function and metabolic control in diabetes mellitus.
Troni, W; Carta, Q; Cantello, R; Caselle, M T; Rainero, I
Measurement of conduction velocity along the H reflex arc was used to study sensorimotor peripheral nerve function in diabetic patients during short- and long-term improvement of hyperglycemia. In ten type I diabetics a slight (p less than 0.05) conduction increase occurred after 6 hours of normal glycemia induced by an artificial endocrine pancreas. Similar but more prominent improvement occurred in twelve type I diabetics treated with continuous subcutaneous insulin injection for 6 months. The results suggest that nerve conduction slowing in diabetic patients stems partly from reversible, nonstructural abnormalities and partly from more slowly reversible morphological or chemical changes in peripheral nerve. PMID:6383190
Microelectronic neural bridging of toad nerves to restore leg function?
Shen, Xiaoyan; Wang, Zhigong; Lv, Xiaoying; Huang, Zonghao
The present study used a microelectronic neural bridge comprised of electrode arrays for neural signal detection, functional electrical stimulation, and a microelectronic circuit including signal amplifying, processing, and functional electrical stimulation to bridge two separate nerves, and to restore the lost function of one nerve. The left leg of one spinal toad was subjected to external mechanical stimulation and functional electrical stimulation driving. The function of the left leg of one spinal toad was regenerated to the corresponding leg of another spinal toad using a microelectronic neural bridge. Oscilloscope tracings showed that the electromyographic signals from controlled spinal toads were generated by neural signals that controlled the spinal toad, and there was a delay between signals. This study demonstrates that microelectronic neural bridging can be used to restore neural function between different injured nerves. PMID:25206698
A study of nerve conduction velocity, late responses and neuromuscular synapse functions in organophosphate workers in India
U. K. Misra; D. Nag; W. A. Khan; P. K. Ray
To study the effect of occupational organophosphate exposure on neuromuscular function, 24 workers exposed to fenthion [0,0-dimethyl-0(4-methyl mercapto-3 methyl phenyl phosphorothioate], whose mean age was 31.7 years (range 22–50) and mean duration of exposure to fenthion 8.5 years (range 1–19) were subjected to detailed clinical and neurophysiological evaluation after spraying. The neurophysiological tests included motor and sensory nerve conduction velocity;
Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model.
Deng, Kangli; Lin, Dan Li; Hanzlicek, Brett; Balog, Brian; Penn, Marc S; Kiedrowski, Matthew J; Hu, Zhiquan; Ye, Zhangqun; Zhu, Hui; Damaser, Margot S
Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury. PMID:25377914
Effect of graded nerve pressure injuries on motor function.
Karasawa, Mika; Yokouchi, Kumiko; Kakegawa, Akira; Kawagishi, Kyutaro; Moriizumi, Tetsuji; Fukushima, Nanae
OBJECT The purpose of this study was to determine the minimum amount of nerve fibers required to maintain normal motor function after nerve injury in rats. METHODS The authors first confirmed that a common peroneal nerve injury caused more aggravating effects on lower limb motor function than tibial nerve injury, as assessed by the static sciatic index (SSI). Thereafter, rats were subjected to varying degrees of crush injury to the common peroneal nerve. At 48 hours after the injury, motor function was assessed using the SSI and slope-walking ability (with slope angles of 30° and 45°). The tibialis anterior muscle, a main muscle innervated by the common peroneal nerve, was removed. Muscle sections were co-labeled with neuronal class III ?-tubulin polyclonal antibody to identify the presence of axons and Alexa Fluor 488-conjugated ?-bungarotoxin to identify the presence of motor endplates. RESULTS The evaluation of neuromuscular innervation showed a correlation between SSI scores and ratios of residual axons (rs = 0.68, p < 0.01), and there was a statistically significant difference between slope-walking ability and ratios of residual axons (p < 0.01). Moreover, the ratios of residual axons in the nerve-crushed rats with normal motor function (SSI above -20) ranged from 36.5% to 88.7%, and those ratios in the success group with slope-walking angles of 30° and 45° ranged from 14.7% to 88.7% and from 39.8% to 88.7%, respectively. CONCLUSIONS In this study of rodents, less than half of the motor axons were sufficient to maintain normal motor function of the lower limb. PMID:25748301
The effect of different warming methods on sensory nerve conduction velocity in shipyard workers occupationally exposed to hand–arm vibration
Martin Cherniack; Anthony J. Brammer; Ronnie Lundstrom; Tim F. Morse; Greg Neely; Tohr Nilsson; Donald Peterson; Esko Toppila; Nicholas Warren; Ulysses Diva; Marc Croteau; Jeffrey Dussetschleger
Objectives Segmental sensory nerve conduction velocity (SNCV) was measured from the wrists to the hands and digits in a population of\\u000a 134 (126 men and 8 women) vibration-exposed shipyard workers following systemic warming using a bicycle ergometer. Results\\u000a were compared to earlier nerve conduction tests, identical in execution, except that the warming process was segmental and\\u000a cutaneous. The study was designed
Erythropoietin Accelerates Functional Recovery After Peripheral Nerve Injury
Elfar, John C.; Jacobson, Justin A.; Puzas, J. Edward; Rosier, Randy N.; Zuscik, Michael J.
Background: Erythropoietin is a naturally occurring hormone with multiple effects on a number of different cell types. Recent data have suggested neuroprotective and perhaps even neurotrophic roles for erythropoietin. We hypothesized that these functional effects could be demonstrable in standard models of peripheral nerve injury. Methods: Experiments were undertaken to evaluate the effect of erythropoietin on the previously reported standard course of healing of sciatic injuries in mice. The injury groups included mice that were subjected to (1) sham surgery, (2) a calibrated sciatic crush injury, (3) transection of the sciatic nerve followed by epineural repair, or (4) a transection followed by burial of the proximal stump in the adjacent muscle tissue (neurectomy). Either erythropoietin or saline solution was administered to the mice in each of these experimental groups twenty-four hours preinjury, immediately after surgical creation of the injury, twenty-four hours postinjury, or one week postinjury. All mice were evaluated on the basis of the published model for recovery of sciatic nerve motor function by measuring footprint parameters at specific times after the injury. Immunohistochemistry was also performed to assess the erythropoietin-receptor expression profile at the site of injury. Results: In general, the mice treated with erythropoietin recovered sciatic nerve motor function significantly faster than did the untreated controls. This conclusion was based on a sciatic function index that was 60% better in the erythropoietin-treated mice at seven days postinjury (p < 0.05). Although the group that had been given the erythropoietin immediately postinjury showed the best enhancement of recovery, the timing of the administration of the drug was not critical. Histological analysis demonstrated enhanced erythropoietin-receptor positivity in the nerves that recovered fastest, suggesting that accelerated healing correlates with expression of the receptor in nerve tissue. Conclusions: Erythropoietin treatment of an acute sciatic nerve crush injury leads to an effect consistent with functional neuroprotection. This protective effect may have clinical relevance, especially since it was detectable even when erythropoietin had been administered up to one week after injury. Clinical Relevance: Erythropoietin may represent a safe therapeutic agent to enhance nerve recovery in humans either after or before "nerve-at-risk" procedures as well as a useful adjunct to treatment of peripheral nerve crush injuries. PMID:18676893
Modulating molecular chaperones improves sensory fiber recovery and mitochondrial function in diabetic peripheral neuropathy.
Urban, Michael J; Pan, Pan; Farmer, Kevin L; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T
Quantification of intra-epidermal nerve fibers (iENFs) is an important approach to stage diabetic peripheral neuropathy (DPN) and is a promising clinical endpoint for identifying beneficial therapeutics. Mechanistically, diabetes decreases neuronal mitochondrial function and enhancing mitochondrial respiratory capacity may aid neuronal recovery from glucotoxic insults. We have proposed that modulating the activity and expression of heat shock proteins (Hsp) may be of benefit in treating DPN. KU-32 is a C-terminal Hsp90 inhibitor that improved thermal hypoalgesia in diabetic C57Bl/6 mice but it was not determined if this was associated with an increase in iENF density and mitochondrial function. After 16 weeks of diabetes, Swiss Webster mice showed decreased electrophysiological and psychosensory responses and a >30% loss of iENFs. Treatment of the mice with ten weekly doses of 20mg/kg KU-32 significantly reversed pre-existing deficits in nerve conduction velocity and responses to mechanical and thermal stimuli. KU-32 therapy significantly reversed the pre-existing loss of iENFs despite the identification of a sub-group of drug-treated diabetic mice that showed improved thermal sensitivity but no increase in iENF density. To determine if the improved clinical indices correlated with enhanced mitochondrial activity, sensory neurons were isolated and mitochondrial bioenergetics assessed ex vivo using extracellular flux technology. Diabetes decreased maximal respiratory capacity in sensory neurons and this deficit was improved following KU-32 treatment. In conclusion, KU-32 improved physiological and morphologic markers of degenerative neuropathy and drug efficacy may be related to enhanced mitochondrial bioenergetics in sensory neurons. PMID:22465570
Neuroselective Current Perception Threshold Evaluation of Bladder Mucosal Sensory Function
Osamu Ukimura; So Ushijima; Hisashi Honjo; Tsuyoshi Iwata; Kei Suzuki; Naoki Hirahara; Koji Okihara; Yoichi Mizutani; Akihiro Kawauchi; Tsuneharu Miki
Objective: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders.Methods: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three
Nerve conduction and electromyography studies.
Kane, N M; Oware, A
Nerve conduction studies (NCS) and electromyography (EMG), often shortened to 'EMGs', are a useful adjunct to clinical examination of the peripheral nervous system and striated skeletal muscle. NCS provide an efficient and rapid method of quantifying nerve conduction velocity (CV) and the amplitude of both sensory nerve action potentials (SNAPs) and compound motor action potentials (cMAPs). The CV reflects speed of propagation of action potentials, by saltatory conduction, along large myelinated axons in a peripheral nerve. The amplitude of SNAPs is in part determined by the number of axons in a sensory nerve, whilst amplitude of cMAPs reflects integrated function of the motor axons, neuromuscular junction and striated muscle. Repetitive nerve stimulation (RNS) can identify defects of neuromuscular junction (NMJ) transmission, pre- or post-synaptic. Needle EMG examination can detect myopathic changes in muscle and signs of denervation. Combinations of these procedures can establish if motor and/or sensory nerve cell bodies or peripheral nerves are damaged (e.g. motor neuronopathy, sensory ganglionopathy or neuropathy), and also indicate if the primary target is the axon or the myelin sheath (i.e. axonal or demyelinating neuropathies). The distribution of nerve damage can be determined as either generalised, multifocal (mononeuropathy multiplex) or focal. The latter often due to compression at the common entrapment sites (such as the carpal tunnel, Guyon's canal, cubital tunnel, radial groove, fibular head and tarsal tunnel, to name but a few of the reported hundred or so 'entrapment neuropathies'). PMID:22614870
Slower nerve conduction velocity in individuals with functional ankle instability.
Simon, J; Docherty, C
The purpose of this study is to quantify nerve conduction velocity differences in individuals with functional ankle instability compared to a "healthy" population. 38 participants ages 18-30 were recruited from a large university with approximately 43,000 students. 19 subjects (9 men and 10 women; age=21.0±1.4 years; height=172.0±9.3?cm; mass=74.4±1 2.4?kg) with symptoms of functional ankle instability were in the functional ankle instability group. 19 subjects (10 men, 9 women; age=22.0±2.6 years; height=169.8±9.1?cm; mass=69.0±14.8?kg) with "healthy" ankles were in the control group. Nerve conduction velocity was conducted using one trial at 2 different sites: posterior to the fibular head (fibular), and 10?cm superior/posterior of the first site (popliteal). Nerve conduction velocity (m/sec) was assessed using a SierraWave II system (Cadwell Laboratories; Kennewick, WA). A MANCOVA was performed on the two dependent variables (fibular and popliteal). Covariates included surface temperature of the leg, body mass index, and age. The independent variable was group (functional ankle instability and control). The effect of group was significantly related to nerve conduction velocity at the fibular site (F(1, 27)?=16.49, p=0.01) and popliteal site (F(1, 27)=4.51, p=0.01), with responses significantly faster for individuals in the control group than the functional ankle instability group. These results indicate that patients with functional ankle instability might have damage to the peroneal nerve which results in slower peroneal nerve conduction velocity. PMID:24577859
Microscale Electrode Implantation during Nerve Repair: Effects on Nerve Morphology, Electromyography, and Recovery of Muscle Contractile Function
Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S
Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves. PMID:21921739
Modified Quad surgery significantly improves the median nerve conduction and functional outcomes in obstetric brachial plexus nerve injury
Background Nerve conduction studies or somatosensory evoked potentials (SSEPs) have become an important tool in the investigation of peripheral nerve lesions, and is sensitive in detecting brachial plexus nerve injury, and other nerve injuries. To investigate whether the modified Quad surgical procedure improves nerve conductivity and functional outcomes in obstetric brachial plexus nerve injury (OBPI) patients. Methods All nerves were tested with direct functional electrical stimulation. A Prass probe was used to stimulate the nerves, and recording the response, the compound motor action potential (CMAP) in the muscle. SSEP monitoring was performed pre- and post modified Quad surgery, stimulating the median and ulnar nerves at the wrist, the radial nerve over the dorsum of the hand, recording the peripheral, cervical and cortical responses. All patients have had the modified Quad surgery (n?=?19). The modified Quad surgery is a muscle release and transfer surgery with nerve decompressions. All patients were assessed preoperatively and postoperatively by evaluating video recordings of standardized movements, the modified Mallet scale to index active shoulder movements. Results The cervical responses were significantly lower in amplitude in the affected arm than the un-affected arm. The median nerve conduction was significantly improved from 8.04 to 9.26 (P?0.022) post-operatively. The shoulder abduction was also significantly improved (pre-op 30° ± 23.3 to 143° ± 33.7, p?0.0001), with a mean follow-up of 43 months after the modified Quad surgery in these patients. Conclusion Median nerve conduction, and shoulder abduction were significantly improved in OBPI children, who have undergone the modified Quad procedure with neuroplasty, internal microneurolysis and tetanic stimulation of the median nerve. PMID:23714699
Topography and ultrastructure of sensory nerve endings in the joint capsules of the Kowari (Dasyuroides byrnei), an Australian marsupial.
Strasmann, T; Halata, Z; Loo, S K
The present investigation in concerned with the topography and ultrastructure of sensory nerve endings in the joint capsules of the Kowari (Dasyuroides byrnei), an Australian marsupial. Material for light and electron microscopy was obtained from shoulder, elbow and knee joint capsules. On the basis of differences in the organization of the connective tissue belonging to the fibrous layer, 3 variants of capsule structure have been distinguished: a rigid, a flaccid and an intermediate type. Whilst the rigid type is characterized by dense connective tissue in the clearly demarcated fibrous layer, the flaccid type shows loose, irregularly arranged connective tissue in the fibrous layer which merges into the synovial layer of the joint capsule. The morphology of the intermediate type corresponds to an intermediate stage between the former two types. In the fibrous layer of the joint capsules three different types of sensory nerve endings were observed: free nerve endings, Ruffini corpuscles and lamellated corpuscles. The free nerve endings are supplied by myelinated afferent axons (1-2 microns in diameter); the terminal thickenings of which are incompletely surrounded by a terminal Schwann cell. Ruffini corpuscles are present in three different varieties: small corpuscles without a perineural capsule predominantly within the flaccid part of the capsule; slightly larger corpuscles with an incomplete perineural capsule and large corpuscles resembling Golgi tendon organs which predominantly occur in the rigid parts of the capsule. The afferent myelinated axons measure 2-4 microns in diameter. The lamellated corpuscles show two variants: small corpuscles with a 2 to 4-layered perineural capsule in the rigid parts of the joint capsules and large corpuscles with two longitudinal clefts of the inner core in the flaccid parts. Both types are supplied by myelinated axons of 3-5 microns in diameter. Thus, in the fibrous layer of the rigid type of joint capsules large Ruffini and small lamellated corpuscles predominate, whereas the fibrous layer of the flaccid type coincides with small Ruffini and large lamellated corpuscles. The present data, therefore, corroborate the concept that the morphology of mechanoreceptors depends upon the texture of the surrounding connective tissue. PMID:3605642
Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique
A. Naukkarinen; I. T. Harvima; M. L. Aalto; R. J. Harvima; M. Horsmanheimo
The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional\\/non-lesional psoriatic and lichen planus skin as well as in healthy control skin.
Olfactory Cilia: Linking Sensory Cilia Function and Human Disease
Jenkins, Paul M.; McEwen, Dyke P.
The olfactory system gives us an awareness of our immediate environment by allowing us to detect airborne stimuli. The components necessary for detection of these odorants are compartmentalized in the cilia of olfactory sensory neurons. Cilia are microtubule-based organelles, which can be found projecting from the surface of almost any mammalian cell, and are critical for proper olfactory function. Mislocalization of ciliary proteins and/or the loss of cilia cause impaired olfactory function, which is now recognized as a clinical manifestation of a broad class of human diseases, termed ciliopathies. Future work investigating the mechanisms of olfactory cilia function will provide us important new information regarding the pathogenesis of human sensory perception diseases. PMID:19406873
TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury
Astrid Tulleuda; Barbara Cokic; Gerard Callejo; Barbara Saiani; Jordi Serra; Xavier Gasull
Background Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the\\u000a S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury.\\u000a Few data are available on the role of leak K2P channels after peripheral axotomy in mammals.\\u000a \\u000a \\u000a \\u000a \\u000a Results Here we describe that rat sciatic nerve axotomy
A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery
Daly, W.; Yao, L.; Zeugolis, D.; Windebank, A.; Pandit, A.
Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative—hollow nerve guidance conduits (NGCs)—have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell–material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic. PMID:22090283
Tachykinin receptors mediating responses to sensory nerve stimulation and exogenous tachykinins and analogues in the rabbit isolated iris sphincter.
Hall, J. M.; Mitchell, D.; Morton, I. K.
1. We have used selective tachykinin receptor agonists and antagonists to investigate the nature of the receptors mediating responses to endogenous and exogenous tachykinins in the rabbit iris sphincter preparation in vitro. 2. The NK1-selective agonist, substance P methyl ester, induced contraction with a pD2 of 9.16 indicating the presence of NK1 receptors. In confirmation, the NK1-selective antagonist, GR82334, competitively antagonized responses to substance P methyl ester with high affinity (pKB 7.46). 3. NK3 receptors also mediate contraction since NK3-selective agonists exhibited high potency, e.g. the pD2 of [Me-Phe7]-neurokinin B was 9.67, and their responses were not inhibited by GR82334 (10 microM). 4. NK2 receptor activation does not seem to contribute to contraction since the NK2-selective agonist [beta-Ala8]-neurokinin A(4-10) had relatively low potency (pD2 6.43), and the NK2-selective antagonists MEN10207 (1 microM) and L-659,877 (10 microM) were inactive or had low affinity, respectively. 5. GR82334 (1 microM) significantly inhibited responses to electrical field-stimulation of non-adrenergic non-cholinergic sensory nerves (3, 10 and 30 Hz), and caused a rightward shift of the log concentration-response curve to bradykinin (lateral shift ca. 1000 fold). Higher concentrations of GR82334 (10 microM) significantly attenuated responses to capsaicin (1-60 microM) whilst completely abolishing responses to field-stimulation (3, 10 and 30 Hz) and bradykinin (1 nM- 3 microM). 6. In conclusion, NK1 and NK3 receptor activation results in contraction of the rabbit iris sphincter. The contractile response following sensory nerve stimulation by bradykinin, capsaicin and electrical field stimulation results from NK1 receptor activation. PMID:8401912
Neural Control of Blood Pressure: Focusing on Capsaicin-Sensitive Sensory Nerves
Youping Wang; Donna H. Wang
Hypertension is a major risk factor leading to devastating cardiovascular events such as myocardial infarction, stroke, heart failure, and renal failure. Despite intensive research in this area, mechanisms underlying essential hyperten- sion remain to be defined. Accumulating evidence indicates that neural components including both sympathetic and sen- sory nerves innervating the cardiovascular and renal tissues play a key role in
On the identification of sensory information from mixed nerves by using single-channel cuff electrodes
Stanisa Raspopovic; Jacopo Carpaneto; Esther Udina; Xavier Navarro; Silvestro Micera
BACKGROUND: Several groups have shown that the performance of motor neuroprostheses can be significantly improved by detecting specific sensory events related to the ongoing motor task (e.g., the slippage of an object during grasping). Algorithms have been developed to achieve this goal by processing electroneurographic (ENG) afferent signals recorded by using single-channel cuff electrodes. However, no efforts have been made
A new paradigm of electrical stimulation to enhance sensory neural function.
Breen, Paul P; ÓLaighin, Gearóid; McIntosh, Caroline; Dinneen, Sean F; Quinlan, Leo R; Serrador, Jorge M
The ability to improve peripheral neural transmission would have significant therapeutic potential in medicine. A technology of this kind could be used to restore and/or enhance sensory function in individuals with depressed sensory function, such as older adults or patients with peripheral neuropathies. The goal of this study was to investigate if a new paradigm of subsensory electrical noise stimulation enhances somatosensory function. Vibration (50Hz) was applied with a Neurothesiometer to the plantar aspect of the foot in the presence or absence of subsensory electrical noise (1/f type). The noise was applied at a proximal site, on a defined region of the tibial nerve path above the ankle. Vibration perception thresholds (VPT) of younger adults were measured in control and experimental conditions, in the absence or presence of noise respectively. An improvement of ?16% in VPT was found in the presence of noise. These are the first data to demonstrate that modulation of axonal transmission with externally applied electrical noise improves perception of tactile stimuli in humans. PMID:24894033
Modelled temperature-dependent excitability behaviour of a single ranvier node for a human peripheral sensory nerve fibre.
Smit, Jacoba E; Hanekom, Tania; Hanekom, Johan J
The objective of this study was to determine whether the Hodgkin-Huxley model for unmyelinated nerve fibres could be modified to predict excitability behaviour at Ranvier nodes. Only the model parameters were modified to those of human, with the equations left unaltered. A model of a single Ranvier node has been developed as part of a larger model to describe excitation behaviour in a generalised human peripheral sensory nerve fibre. Parameter values describing the ionic and leakage conductances, corresponding equilibrium potentials, resting membrane potential and membrane capacitance of the original Hodgkin-Huxley model were modified to reflect the corresponding parameter values for human. Parameter temperature dependence was included. The fast activating potassium current kinetics were slowed down to represent those of a slow activating and deactivating potassium current, which do not inactivate. All calculations were performed in MATLAB. Action potential shape and amplitude were satisfactorily predicted at 20, 25 and 37 degrees C, and were not influenced by activation or deactivation of the slow potassium current. The calculated chronaxie time constant was 65.5 micros at 37 degrees C. However, chronaxie times were overestimated at temperatures lower than body temperature. PMID:19066936
Characterization of Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis
Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.
Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814
Exercise training improves functional recovery and motor nerve conduction velocity after sciatic nerve crush lesion in the rat
Nico L. U. van Meeteren; Jan H. Brakkee; Frank P. T. Hamers; Paul J. M. Helders; Willem H. Gispen
Objective: To observe the effects of exercise training on recuperation of sensorimotor function in the early phase of regeneration, and to monitor the long-term effects of exercise on electrophysiological aspects of the regenerating nerve.Design: After sciatic nerve crush in 20 male Wistar rats, one random selected group was subjected to 24 days of exercise training, whereas the other group served
Sensory nerves, vascular endothelium and neurogenic relaxation of the guinea-pig isolated pulmonary artery
Carlo Alberto Maggi; Riccardo Patacchini; Francesca Perretti; Manuela Tramontana; Stefano Manzini; Pierangelo Geppetti; Paolo Santicioli
1. In the presence of atropine and guanethidine (3 µmol\\/l each), electrical field stimulation (1–20 Hz) produced frequency-dependent relaxations of the histamine-(3 µmol\\/l) induced vascular tone in isolated rings from the guinea-pig pulmonary artery. The electrically-evoked relaxations were abolished by tetrodotoxin (1 µmol\\/l). The amplitude of these nerve-mediated, nonadrenergic non-cholinergic (NANC) relaxations was unaffected by removal of the vascular endothelium
Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats
Petra Hartmann; Renáta Varga; Zsuzsanna Zobolyák; Júlia Héger; Blanka Cs?sz; István Németh; Zsolt Rázga; Csaba Vízler; Dénes Garab; Péter Sántha; Gábor Jancsó; Mihály Boros; Andrea Szabó
We have shown that ischaemic preconditioning ameliorates both the local periosteal and the systemic leukocyte activation evoked\\u000a by limb ischaemia–reperfusion. We hypothesized that the activation of chemosensitive afferent nerves by transient ischaemia\\u000a contributes to the protective mechanisms of ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent\\u000a mechanism. In Sprague–Dawley rats, 60-min complete limb ischaemia was followed by 180 min of reperfusion.
The role of reactive oxygen species and capsaicin-sensitive sensory nerves in the pathomechanisms of gastric ulcers induced by stress.
Kwiecie?, S; Brzozowski, T; Konturek, P C; Pawlik, M W; Pawlik, W W; Kwiecie?, N; Konturek, S J
Gastric microcirculation plays an important role in the maintenance of the gastric mucosal barrier and mucosal integrity. Sensory nerves are involved in the regulation of mucosal blood circulation and mucosal defense. Therefore, the ablation of these nerves by neurotoxic doses of capsaicin provides the possibility of determination of their role in gastric mucosal integrity. Stress ulceration represents a serious gastric lesions. Results of our previous experiments have indicated that water immersion and restraint stress (WRS) led to increased oxidative metabolism. Ablation of sensory nerves by high doses of capsaicin retards healing of gastric ulcers, but the role of reactive oxygen species (ROS) in the healing process has been little studied. Therefore, the aim of our present investigations was to determine the participation of ROS in sensory nerve activity during WRS. Experiments were carried out on 90 male Wistar rats and the area of gastric lesions was measured by planimetry. Colorimetric assays were used to determine gastric mucosal levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), as well as superoxide dismutase (SOD) activity. We demonstrated that inactivation of sensory nerves resulted in magnification of gastric mucosal damage induced by the WRS. In this process, oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity, could play an important role. Aspirin, applied in a low dose, exerts a protective activity, possibly due to its metabolites, which possess the anti-oxidant and ROS scavanging properties. Pentoxyfilline-induced gastroprotection and hyperemia depends upon attenuation of the oxidative stress. This protection and hyperemia were, at least in part, attenuated by ASA. PMID:14566080
Targeted Expression of a Multifunctional Chimeric Neurotrophin in the Lesioned Sciatic Nerve Accelerates Regeneration of Sensory and Motor Axons
Hiroshi Funakoshi; Marten Risling; Thomas Carlstedt; Urban Lendahl; Tonis Timmusk; Madis Metsis; Yuji Yamamoto; Carlos F. Ibanez
Peripheral nerve injury markedly regulates expression of neurotrophins and their receptors in the lesioned nerve. However, the role of endogenously produced neurotrophins in the process of nerve regeneration is unclear. Expression of a multifunctional neurotrophin, panneurotrophin-1 (PNT-1), was targeted to the peripheral nerves of transgenic mice by using a gene promoter that is specifically activated after nerve lesion but that
Asymptomatic small fiber neuropathy in diabetes mellitus: investigations with intraepidermal nerve fiber density, quantitative sensory testing and laser-evoked potentials.
Ragé, Michael; Van Acker, Nathalie; Knaapen, Michiel W M; Timmers, Maarten; Streffer, Johannes; Hermans, Michel P; Sindic, Christian; Meert, Theo; Plaghki, Léon
This study aimed at evaluating the performance of a battery of morphological and functional tests for the assessment of small nerve fiber loss in asymptomatic diabetic neuropathy (DNP). Patients diagnosed for ?10 years with type 1 (n = 10) or type 2 (n = 13) diabetes mellitus (DM) without conventional symptoms or signs of DNP were recruited and compared with healthy controls (n = 18) and patients with overt DNP (n = 5). Intraepidermal nerve fiber density (IENFd) was measured with PGP9.5 immunostaining on punch skin biopsies performed at the distal leg. Functional tests consisted of quantitative sensory testing (QST) for light-touch, cool, warm and heat pain detection thresholds and brain-evoked potentials with electrical (SEPs) and CO(2) laser stimulation [laser-evoked potentials (LEPs)] of hand dorsum and distal leg using small (0.8 mm(2)) and large (20 mm(2)) beam sizes. Results confirmed a state of asymptomatic DNP in DM, but only at the distal leg. Defining a critical small fiber loss as a reduction of IENFd ?-2 z scores of healthy controls, this state prevailed in type 2 (30%) over type 1 DM (10%) patients despite similar disease duration and current glycemic control. LEPs with the small laser beam performed best in terms of sensitivity (91%), specificity (83%) and area-under-the ROC curve (0.924). Although this performance was not statically different from that of warm and cold detection threshold, LEPs offer an advantage over QST given that they bypass the subjective report and are therefore unbiased by perceptual factors. PMID:21472496
Identity of Myelinated Cutaneous Sensory Neurons Projecting to Nocireceptive Laminae Following Nerve Injury in Adult Mice
WOODBURY, C. JEFFERY; KULLMANN, FLORENTA A.; McILWRATH, SABRINA L.; KOERBER, H. RICHARD
It is widely thought that, after peripheral injury, some low-threshold mechanoreceptive (LTMR) afferents "sprout" into pain-specific laminae (I–II) of the dorsal horn and are responsible for chronic pain states such as mechanical allodynia. Although recent studies have questioned this hypothesis, they fail to account for a series of compelling results from single-fiber analyses showing extensive projections from large-diameter myelinated afferents into nocireceptive layers after nerve injury. Here we show that, in the thoracic spinal cord of naďve adult mouse, all myelinated nociceptors gave rise to terminal projections throughout the superficial dorsal horn laminae (I–II). Most (70%) of these fibers had large-diameter axons with recurving flame-shaped central arbors that projected throughout the dorsal horn laminae I–V. This morphology was reminiscent of that attributed to sprouted LTMRs described in previous studies. After peripheral nerve axotomy, we found that LTMR afferents with narrow, uninflected somal action potentials did not sprout into superficial laminae of the dorsal horn. Only myelinated noiceptive afferents with broad, inflected somal action potentials were found to give rise to recurving collaterals and project into superficial "pain-specific" laminae after axotomy. We conclude that the previously undocumented central morphology of large, myelinated cutaneous nociceptors may very well account for the morphological findings previously thought to require sprouting of LTMRs. PMID:18335545
Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation
Paris-Sud XI, Université de
Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation Chloe´ A. Picq1'He´pato- Gastroente´rologie, CHU de Grenoble, Grenoble, France Abstract Vagus nerve stimulation (VNS) has been on Immune Functions in a Rat Model of Vagus Nerve Stimulation. PLoS ONE 8(6): e67086. doi:10.1371/journal
Endogenous prostaglandins and afferent sensory nerves in gastroprotective effect of hydrogen sulfide against stress-induced gastric lesions.
Magierowski, Marcin; Jasnos, Katarzyna; Kwiecien, Slawomir; Drozdowicz, Danuta; Surmiak, Marcin; Strzalka, Malgorzata; Ptak-Belowska, Agata; Wallace, John L; Brzozowski, Tomasz
Hydrogen sulfide (H2S) plays an important role in human physiology, exerting vasodilatory, neuromodulatory and anti-inflammatory effects. H2S has been implicated in the mechanism of gastrointestinal integrity but whether this gaseous mediator can affect hemorrhagic lesions induced by stress has been little elucidated. We studied the effect of the H2S precursor L-cysteine, H2S-donor NaHS, the H2S synthesizing enzyme (CSE) activity inhibitor- D,L-propargylglycine (PAG) and the gastric H2S production by CSE/CBS/3-MST activity in water immersion and restraint stress (WRS) ulcerogenesis and the accompanying changes in gastric blood flow (GBF). The role of endogenous prostaglandins (PGs) and sensory afferent nerves releasing calcitonin gene-related peptide (CGRP) in the mechanism of gastroprotection induced by H2S was examined in capsaicin-denervated rats and those pretreated with capsazepine to inhibit activity of vanilloid receptors (VR-1). Rats were pretreated with vehicle, NaHS, the donor of H2S and or L-cysteine, the H2S precursor, with or without the concurrent treatment with 1) nonselective (indomethacin) and selective cyclooxygenase (COX)-1 (SC-560) or COX-2 (rofecoxib) inhibitors. The expression of mRNA and protein for COX-1 and COX-2 were analyzed in gastric mucosa pretreated with NaHS with or without PAG. Both NaHS and L-cysteine dose-dependently attenuated severity of WRS-induced gastric lesions and significantly increased GBF. These effects were significantly reduced by pretreatment with PAG and capsaicin denervation. NaHS increased gastric H2S production via CSE/CBS but not 3-MST activity. Inhibition of COX-1 and COX-2 activity significantly diminished NaHS- and L-cysteine-induced protection and hyperemia. NaHS increased expression of COX-1, COX-2 mRNAs and proteins and raised CGRP mRNA expression. These effects of NaHS on COX-1 and COX-2 protein contents were reversed by PAG and capsaicin denervation. We conclude that H2S exerts gastroprotection against WRS-induced gastric lesions by the mechanism involving enhancement in gastric microcirculation mediated by endogenous PGs, sensory afferent nerves releasing CGRP and the activation of VR-1 receptors. PMID:25774496
Preservation of Facial Nerve Function Repaired by Using Fibrin Glue-Coated Collagen Fleece for a Totally Transected Facial Nerve during Vestibular Schwannoma Surgery.
Choi, Kyung-Sik; Kim, Min-Su; Jang, Sung-Ho; Kim, Oh-Lyong
Recently, the increasing rates of facial nerve preservation after vestibular schwannoma (VS) surgery have been achieved. However, the management of a partially or completely damaged facial nerve remains an important issue. The authors report a patient who was had a good recovery after a facial nerve reconstruction using fibrin glue-coated collagen fleece for a totally transected facial nerve during VS surgery. And, we verifed the anatomical preservation and functional outcome of the facial nerve with postoperative diffusion tensor (DT) imaging facial nerve tractography, electroneurography (ENoG) and House-Brackmann (HB) grade. DT imaging tractography at the 3rd postoperative day revealed preservation of facial nerve. And facial nerve degeneration ratio was 94.1% at 7th postoperative day ENoG. At postoperative 3 months and 1 year follow-up examination with DT imaging facial nerve tractography and ENoG, good results for facial nerve function were observed. PMID:25024825
30 July 2009 Worms with a single functional sensory cilium generate proper neuron-specific
Schafer, William R.
of these sensory neurons are located throughout the body, where they are responsible for sensing body touch1 30 July 2009 Worms with a single functional sensory cilium generate proper neuron Keywords: DAF-19, RFX transcription factor, ciliated sensory neuron (CSN), FRISSC, behavioral assays
Novel targeted sensory reinnervation technique to restore functional hand sensation after transhumeral amputation.
Hebert, Jacqueline S; Olson, Jaret L; Morhart, Michael J; Dawson, Michael R; Marasco, Paul D; Kuiken, Todd A; Chan, K Ming
We present a case study of a novel variation of the targeted sensory reinnervation technique that provides additional control over sensory restoration after transhumeral amputation. The use of intraoperative somatosensory evoked potentials on individual fascicles of the median and ulnar nerves allowed us to specifically target sensory fascicles to reroute to target cutaneous nerves at a distance away from anticipated motor sites in a transhumeral amputee. This resulted in restored hand maps of the median and ulnar nerve in discrete spatially separated areas. In addition, the subject was able to use native and reinnervated muscle sites to control a robotic arm while simultaneously sensing touch and force feedback from the robotic gripper in a physiologically correct manner. This proof of principle study is the first to demonstrate the ability to have simultaneous dual flow of information (motor and sensory) within the residual limb. In working towards clinical deployment of a sensory integrated prosthetic device, this surgical method addresses the important issue of restoring a usable access point to provide natural hand sensation after upper limb amputation. PMID:24760915
Near-terminus axonal structure and function following rat sciatic nerve regeneration through a collagen-GAG matrix in a ten-millimeter gap.
Chamberlain, L J; Yannas, I V; Hsu, H P; Strichartz, G R; Spector, M
The objectives of this study were to evaluate the regenerated axon structure at near-terminal locations in the peroneal and tibial branches 1 year following implantation of several tubular devices in a 10-mm gap in the adult rat sciatic nerve and to determine the extent of recovery of selected sensory and motor functions. The devices were collagen and silicone tubes implanted alone or filled with a porous collagen-glycosaminoglycan matrix. Intact contralateral nerves and autografts were used as controls. Nerves were retrieved at 30 and 60 weeks postoperatively for histological evaluation of the number and diameter of regenerated axons proximal and distal to the gap and in the tibial and peroneal nerve branches, near the termination point. Several functional evaluation methods were employed: gait analysis, pinch test, muscle circumference, and response to electrical stimulation. A notable finding was that the matrix-filled collagen tube group had a significantly greater number of large-diameter myelinated axons (> or =6 microm in diameter) in the distal nerve branches than any other group, including the autograft group. These results were consistent with previously reported electrophysiological measurements that showed that the action potential amplitude for the A fibers in the matrix-filled collagen tube group was greater than for the autograft control group. Functional testing revealed the existence of both sensory and motor recovery following peripheral nerve regeneration through all devices; however, the tests employed in this study did not show differences among the groups with regeneration. Electrical stimulation in vivo showed that threshold parameters to elicit muscle twitch were the same for reinnervating and control nerves. The investigation is of importance in showing for the first time the superiority of a specific fully resorbable off-the-shelf device over an autograft for bridging gaps in peripheral nerve, with respect to the near-terminus axonal structure. PMID:10820438
The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury
B. Kalmar; L. Greensmith; M. Malcangio; S. B. McMahon; P. Csermely; G. Burnstocke
In this study, we examined the effect BRX-220, a co-inducer of heat shock proteins, in injury-induced peripheral neuropathy. Following sciatic nerve injury in adult rats and treatment with BRX-220, the following features of the sensory system were studied: (a) expression of calcitonin gene-related peptide (CGRP); (b) binding of isolectin B4 (IB4) in dorsal root ganglia (DRG) and spinal cord; (c)
Monkey median nerve repaired by nerve graft or collagen nerve guide tube.
Archibald, S J; Shefner, J; Krarup, C; Madison, R D
Nerve regeneration was followed in 15 median and 1 ulnar nerve of eight Macaca fascicularis monkeys by serial electrophysiological assessments over a period of three and a half years. Nerve gaps of 5 mm at the wrist were bridged by collagen-based nerve guides, nerve autografts, or direct suture repairs. Thenar muscle reinnervation occurred between 50 and 70 d for all groups, indicating axonal elongation rates of approximately 1 mm/d. The recovery rates of the compound muscle action potential (CMAP) and the compound sensory action potential (CSAP) amplitudes were significantly slower after direct suture repair compared to the other two procedures, although the final levels of recovery were all comparable. Similar results were achieved in one median and one ulnar nerve following nerve guide repair of a 15 mm nerve gap. The functional reinnervation of Pacinian corpuscles was detected in all cases following either nerve graft or nerve guide repair, with similar amplitudes and latencies of the tactile evoked CSAP for both types of repair. Histological analysis demonstrated a significant increase in the number of myelinated axons in the median nerve distal to the nerve lesions following both nerve graft and nerve guide repairs compared to proximal and normal controls, with significant reductions of fiber diameter and corresponding increases in g-ratio. The return of a bimodal frequency distribution of myelinated axon fiber diameter was confirmed by three-dimensional surface plots which illustrate the frequency distribution of the relationship between fiber diameter and g-ratio. These combined results demonstrate that nerve regeneration after repair of a 5 mm nerve gap with a collagen nerve guide in the nonhuman primate is similar to that after graft repair, and the final level of physiological recovery for both repair procedures is comparable to direct suture repair of the median nerve. PMID:7751969
Displacement of the contents of dentinal tubules and sensory transduction in intradental nerves of the cat.
Andrew, D; Matthews, B
Experiments were performed on anaesthetized cats to test the hypothesis that fluid flow through dentinal tubules is part of the mechanism involved in the transduction of pain-producing stimuli in teeth. In 11 animals, fluid flow through dentine and single- and multi-unit activity in intradental nerves were recorded simultaneously during the application of changes in hydrostatic pressure (-500 to +500 mm Hg) to exposed dentine. Seventeen A-fibres (conduction velocity (CV), 10.6-55.1 m s(-1)) were isolated that were pressure sensitive. The thresholds of these units in terms of dentinal fluid flow were in the range 0.3-2.1 nl s(-1) mm(-2) during outward flow from the pulp and 2.0-3.5 nl s(-1) mm(-2) during inward flow. All the units were more sensitive to outward than inward flow. Twenty-eight units (CV, 0.6-48.8 m s-1) were not pressure sensitive, and 12 of these had conduction velocities in the C-fibre range (< 2.5 m s(-1)). The velocities of the tubular contents were calculated by estimating the number and diameters of dentinal tubules exposed. At the threshold of single-fibre responses these velocities were in the range 31.7-222.9 microm s(-1) during outward flow 211.4-369.6 microm s-1 during inward flow. Repetitive pressure stimulation of dentine resulted in a progressive reduction in the evoked discharge, which was probably due to pulp damage. In seven animals, 10 single intradental nerve fibres were selected that responded to hydrostatic pressure stimuli and their responses to the application of hot, cold, osmotic, mechanical and drying stimuli to exposed dentine were investigated. With these stimuli dentinal fluid flow could not be recorded in vivo for technical reasons and was therefore recorded in vitro after completion of the electrophysiological recordings. With each form of stimulus, the discharge evoked in vivo was closely related to the flow predicted from the in vitro measurements. The results were therefore consistent with the hypothesis that the stimuli act through a common transduction mechanism that involves fluid flow through dentine. PMID:11118506
Can amino-functionalized carbon nanotubes carry functional nerve growth factor?
Chen, Wen; Xiong, Qing; Ren, Quanxia; Guo, Yake; Li, Gao
Carbon nanotubes can carry protein into cells to induce biological effects. Amino-functionalized carbon nanotubes are soluble and biocompatible, have high reactivity and low toxicity, and can help promote nerve cell growth. In this study, amino-functionalized ethylenediamine-treated multi-walled carbon nanotubes were used to prepare carbon nanotubes-nerve growth factor complexes by non-covalent grafting. The physicochemical properties, cytotoxicity to PC12 and chick embryo dorsal root ganglion, and biological activity of the carbon nanotubes-nerve growth factor complexes were investigated. The results showed that amino functionalization improved carbon nanotubes-nerve growth factor complex dispersibility, reduced their toxicity to PC12 cells, and promoted PC12 cell differentiation and chick embryo dorsal root ganglion. PMID:25206814
Low-Level Laser Irradiation Improves Functional Recovery and Nerve Regeneration in Sciatic Nerve Crush Rat Injury Model
Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin
The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm2 and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm2. Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm2 had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm2. Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm2. Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm2 and 8 J/cm2) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID:25119457
Relationships among Repetitive Behaviors, Sensory Features, and Executive Functions in High Functioning Autism.
Boyd, Brian A; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T; Bodfish, James W
This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N = 61) were compared to healthy, typical controls (N = 64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction explained any relationship between the variables. Particular types of repetitive behavior (i.e., stereotypy and compulsions) were related to sensory features in autism; however, executive deficits were only correlated with repetitive behavior. This finding suggests that executive dysfunction is not the shared neurocognitive mechanism that accounts for the relationship between restricted, repetitive behaviors and aberrant sensory features in HFA. Group status, younger chronological age, presence of sensory processing issues, and difficulties with behavior regulation predicted the presence of repetitive behaviors in the HFA group. PMID:21475640
Vesicourethral function in diabetic patients: association of abnormal nerve conduction velocity with vesicourethral dysfunction.
Mitsui, T; Kakizaki, H; Kobayashi, S; Morita, H; Matsumura, K; Koyanagi, T
This study was undertaken to examine diabetic vesicourethral dysfunction in association with nerve conduction velocity. Uroflowmetry, water cystometry, International Prostate Symptom Score (IPSS), and nerve conduction velocity were analyzed in 29 diabetic patients (21 men and eight women; a mean age, 58.0 years). Nerve conduction velocity was measured for sensory nerve conduction velocity (SCV) of the sural nerve and motor nerve conduction velocity (MCV) of the peroneal nerve. Normal voiding was defined as continuous flow at the normal flow rate and residual urine <50 mL. Results of uroflowmetry and cystometry were compared with those of nerve conduction velocity. Eleven of 29 patients (38%) had voiding dysfunction. A vesical denervation supersensitivity test was negative in all patients. The mean IPSS was not significant different between patients with or without voiding dysfunction. Incidence of bladder volume at first desire to void >300 mL and maximum bladder capacity >500 mL were significantly higher in patients with abnormal SCV than those with normal SCV (P < 0.03 and 0.001, respectively). Eleven of 16 patients with abnormal MCV showed voiding dysfunction, whereas all patients with normal MCV showed normal voiding (P < 0.001). These results suggest that lower urinary tract symptoms alone cannot predict diabetic vesicourethral dysfunction and that diabetic vesicourethral dysfunction is highly correlated with abnormal nerve conduction velocity. Neurourol. Urodynam. 18:639-645, 1999. PMID:10529712
Altered Function of Lumbar Nerve Roots in Patients With Transitional Lumbosacral Vertebrae
Han Soo Chang; Hiroshi NAKAGAWA
STUDY DESIGN: A retrospective study was conducted on the preoperative neurologic symptoms of patients with lumbar herniated discs. OBJECTIVE: To evaluate the possibility that the muscle innervation pattern and the sensory dermatomes of lumbar nerve roots are altered when a lumbosacral transitional vertebra is present. SUMMARY OF BACKGROUND DATA: In 1962, McCulloch et al suggested with intraoperative recordings that the
New Chemically Functionalized Nanomaterials for Electrical Nerve Agents Sensors
NASA Astrophysics Data System (ADS)
Simonato, Jean-Pierre; Clavaguera, Simon; Carella, Alexandre; Delalande, Michael; Raoul, Nicolas; Lenfant, Stephane; Vuillaume, Dominique; Dubois, Emmanuel
A chemical receptor specific to traces of organophosphorus nerve agents (OPs) has been synthesized and grafted to carbon nanotubes and silicon nanowires in order to make electrical sensors. Our results show that it is possible to detect efficiently sub-ppm traces of OPs with excellent selectivity notably with the use of silicon nanowires by monitoring the Drain-Source current of the SiNW-FET at an optimum back Gate voltage as a function of time. First developments of a prototype have also been realized.
A Silicon Model of Auditory-Nerve Response Nonlinear signal processing is an integral part of sensory transduction in
Lazzaro, John
part of sensory transduction in the nervous system. Sensory inputs are analog, continuous-time signals the sound energy present at the eardrum into the first neural representation of the auditory system
Sensory deficit in Parkinson's disease: evidence of a cutaneous denervation.
Nolano, Maria; Provitera, Vincenzo; Estraneo, Anna; Selim, Mona M; Caporaso, Giuseppe; Stancanelli, Annamaria; Saltalamacchia, Anna Maria; Lanzillo, Bernardo; Santoro, Lucio
Sensory disturbances are part of the clinical picture of Parkinson's disease. Abnormalities in sensory processing, through a basal ganglia involvement, are thought to be responsible for the sensory dysfunction since sensory nerve conduction velocity (NCV) is usually normal. However, NCV does not examine small fibres or terminal endings of large sensory fibres, whereas skin biopsy is more suitable for these purposes. To evaluate peripheral sensory nerves in Parkinson's disease, we studied cutaneous free and encapsulated sensory nerve endings in 18 patients and 30 healthy controls using 3-mm punch biopsies from glabrous and hairy skin. Ten patients had additional skin biopsies from the contralateral side. Further evaluation included NCV and Quantitative Sensory Testing. Parkinson's disease patients showed a significant increase in tactile and thermal thresholds (P < 0.01), a significant reduction in mechanical pain perception (P < 0.01) and significant loss of epidermal nerve fibres (ENFs) and Meissner corpuscles (MCs) (P < 0.01). In patients with bilateral biopsies, loss of pain perception and ENFs was higher on the more affected side (P < 0.01). We found evidence suggesting attempts at counteracting degenerative processes as increased branching, sprouting of nerves and enlargement of the vascular bed. Morphological and functional findings did not correlate with age or disease duration. Disease severity correlated with loss of MCs and reduction in cold perception and pain perception. We demonstrated a peripheral deafferentation in Parkinson's disease that could play a major role in the pathogenesis of the sensory dysfunction. PMID:18515869
Acute small fibre sensory neuropathy: another variant of Guillain-Barré syndrome?
Seneviratne, U; Gunasekera, S
The clinical features and normal routine nerve conduction studies, which assess large diameter nerve fibre function, indicate small sensory fibre dysfunction in the group. Their presentation and CSF findings would fit into the diagnosis of sensory Guillain-Barré syndrome. The current study suggests that acute small fibre sensory neuropathy (ASFSN) is another clinical entity which could perhaps be included in the heterogeneous range of Guillain-Barré syndrome. PMID:11909922
The sensory innervation of the pineal organ in the lizard, Lacerta viridis , with remarks on its position in the trend of pineal phylogenetic structural and functional evolution
J. Ariëns Kappers
The sensory innervation of the pineal organ of adult Lacerta viridis has been investigated. Some specimens of Lacerta muralis lillfordi were also used. In the pineal epithelium, a small number of nerve cell pericarya of a sensory type are present. They lie either solitary or in small clusters close to the basement membrane. The axons originating from the nerve cell
Expression and Function of Nerve Growth Factor and Nerve Growth Factor Receptor on Cultured Keratinocytes
Carlo Pincelli; Cinzia Sevignani; Rossella Manfredini; Alexis Grande; Fabrizio Fantini; Luisa Bracci-Laudiero; Luigi Aloe; Sergio Ferrari; Andrea Cossarizza; Alberto Giannetti
Keratinocytes, a key cellular component both for homeostasis and pathophysiologic processes of the skin, secrete a number of cytokines and are stimulated by several growth factors. Nerve growth factor (NGF) is synthesized in the skin and basal keratinocytes express the low-affinity nerve growth factor receptor (NGF-R). We present evidence that normal human keratinocytes in culture express the low- and the
Sympathetic sprouting and changes in nociceptive sensory innervation in the glabrous skin of the rat hind paw following partial peripheral nerve injury.
Yen, Laurene D; Bennett, Gary J; Ribeiro-da-Silva, Alfredo
Previous studies have suggested that sympathetic sprouting in the periphery may contribute to the development and persistence of sympathetically maintained pain in animal models of neuropathic pain. In the present study, we examined changes in the cutaneous innervation in rats with a chronic constriction injury to the sciatic nerve. At several periods postinjury, hind paw skin was harvested and processed by using a monoclonal antibody against dopamine-beta-hydroxylase to detect sympathetic fibers and a polyclonal antibody against calcitonin gene-related peptide to identify peptidergic sensory fibers. We observed migration and branching of sympathetic fibers into the upper dermis of the hind paw skin, where they were normally absent. This migration was first detected at 2 weeks, peaked at 4-6 weeks, and lasted for at least 20 weeks postlesion. At 8 weeks postlesion, there was a dramatic increase in the density of peptidergic fibers in the upper dermis. Quantification revealed that densities of peptidergic fibers 8 weeks postlesion were significantly above levels in sham animals. The ectopic sympathetic fibers did not innervate blood vessels but formed a novel association and wrapped around sprouted peptidergic nociceptive fibers. Our data show a long-term sympathetic and sensory innervation change in the rat hind paw skin after the chronic constriction injury. This novel fiber arrangement after nerve lesion may play an important role in the development and persistence of sympathetically maintained neuropathic pain after partial nerve lesions. PMID:16506190
Relationships among Repetitive Behaviors, Sensory Features, and Executive Functions in High Functioning Autism
ERIC Educational Resources Information Center
Boyd, Brian A.; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T.; Bodfish, James W.
This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N = 61) were compared to healthy, typical controls (N = 64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction…
Dexamethasone Enhanced Functional Recovery after Sciatic Nerve Crush Injury in Rats
Feng, Xinhong; Yuan, Wei
Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects. PMID:25839037
Dexamethasone enhanced functional recovery after sciatic nerve crush injury in rats.
Feng, Xinhong; Yuan, Wei
Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects. PMID:25839037
Effects of ibogaine on sensory-motor function, activity, and spatial learning in rats
Raymond P. Kesner; Pamela Jackson-Smith; Clarissa Henry; Kelly Amann
Ibogaine, a naturally occurring alkaloid, has been show to reduce naloxone-precipitated withdrawal symptoms from morphine. Given the clinical possibilities, it is important to determine ibogaine's effects on sensory-motor function, activity, learning, and memory. Long-Evans rats injected with doses of 20–60 mg\\/kg of ibogaine displayed slower response times on sensory and sensory-motor tests and were impaired in performing specific motor reflexes
Prediction of Facial Nerve Function After Surgery for Cerebellopontine Angle Tumors
Kirkpatrick, P. J.; Watters, G.; Strong, A. J.; Walliker, J. R.; Gleeson, M. J.
A series of 18 patients undergoing surgery for cerebellopontine angle tumors is reported. Patients were grouped according to size of tumor (0 to 2.5 cm, 11 cases; more than 2.5 cm, 7 cases). In all, the facial nerve was identified and conductance assessed by monitoring the facial electromyographic response to facial nerve stimulation. Postoperative facial nerve function was graded clinically after 3 months according to the House scale. Tumor removal was complete in all cases. In patients with tumors up to 2.5 cm the facial nerve was intact to visual inspection at the end of the procedure in all but one, where partial division was evident. In this group intraoperative facial nerve stimulation indicated electrical integrity in 8 of the 11 cases, all of which regained good facial nerve function postoperatively (House grades I and II). Nerve conduction was lost during the operation in the remaining three patients with small tumors; two subsequently developed a moderately severe (grade IV) dysfunction and the third, a total paralysis (grade VI). In the large (more than 2.5 cm) tumor group the facial nerve was anatomically intact in five of the seven cases, partially divided in one, and completely sectioned in the remaining case. Facial nerve stimulation indicated functional integrity in three patients, two of whom developed moderate (grade III) and the third a severe (grade V) dysfunction. In the other four cases nerve function could not be detected at operation; three of these developed a moderate facial nerve dysfunction (grade III/IV) and the final case a complete paralysis (grade VI). Intraoperative facial nerve monitoring appeared to predict eventual facial function accurately in the small tumor group, but did not predict facial nerve recovery reliably following surgery for larger tumors. PMID:17170808
Vanilloid receptors in the urinary bladder: regional distribution, localization on sensory nerves, and species-related differences
Arpad Szallasi; Bruno Conte; Cristina Goso; Peter M. Blumberg; Stefano Manzini
Using selective surgical ablations we have investigated the localization of vanilloid receptors (specific [3H]resiniferatoxin binding sites) on terminals of the pelvic, hypogastric, and pudendal nerves in the rat urinary bladder. Pelvic and hypogastric nerve resections resulted in 90%6 and 25% loss of specific [3H]resiniferatoxin (RTX) binding sites, respectively, whilst pudendic nerve resection had no measurable effect on the binding. In
Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings
Passmore, Gayle M.; Reilly, Joanne M.; Thakur, Matthew; Keasberry, Vanessa N.; Marsh, Stephen J.; Dickenson, Anthony H.; Brown, David A.
M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 ?M XE991 sensitized A?- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32°C in many A?-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on A?-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive A?-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991. PMID:22593734
Painful and non-painful neuropathy in HIV-infected patients: an analysis of somatosensory nerve function.
Martin, Claes; Solders, Göran; Sönnerborg, Anders; Hansson, Per
Fifteen to 50% of AIDS-patients suffer from distal predominantly sensory neuropathy (DSP), which is commonly associated with painful symptoms. In the present study, we have focused on the function of fine calibre nerve channels, in 36 consecutive HIV-1-infected patients with painful (PPN) (n=20; 54%) and non-painful (PN) (n=16) sensory neuropathy, assessed by clinical, quantitative thermal testing (QTT) (31/36), and peripheral nerve conduction examination (32/36). Control QTT data were obtained from 49 healthy subjects with a corresponding age- and sex distribution. Demographics, antiviral treatment, immunological status, and nerve conduction examination did not differ between patients with and without painful symptoms. Hypoaesthesia to warmth, cold, and heat pain was observed in both neuropathy groups when compared to healthy controls. However, the perception threshold to warmth was more often impaired (p<0.01) and the level of impairment was more pronounced (p<0.001) in patients with painful neuropathy. Furthermore, increased pain sensitivity to cold was found only in patients with painful symptoms (p<0.05). An abnormal outcome of any QTT parameter was found in all patients with pain, but only among 62% of patients without pain, p<0.01, and the cumulative frequency of abnormalities in any of the four thermal percepts (warmth, cold, heat pain, and cold pain) was higher in patients with painful symptoms, p<0.0001. This study demonstrates a more pronounced impairment of C-fibre-mediated innocuous warm perception in patients with painful neuropathy, which in the setting of impaired or absent heat pain perception suggests a more generalised loss of function in somatosensory C-fibre channels. PMID:12527314
Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.
Wood, Matthew D; Gordon, Tessa; Kemp, Stephen W P; Liu, Edward H; Kim, Howard; Shoichet, Molly S; Borschel, Gregory H
The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation. PMID:23239194
Brain gangliosides: Functional ligands for myelin stability and the control of nerve regeneration
Alka A. Vyas; Ronald L. Schnaar
Gangliosides, sialylated glycosphingolipids which are the predominant glycans on vertebrate nerve cell surfaces, are emerging as components of membrane rafts, where they can mediate important physiological functions. Myelin associated glycoprotein (MAG), a minor constituent of myelin, is a sialic acid binding lectin with two established physiological functions: it is involved in myelin-axon stability and cytoarchitecture, and controls nerve regeneration. MAG
A (heat) shock to the system promotes peripheral nerve regeneration
Höke, Ahmet
Peripheral nerves are easily damaged, resulting in loss of motor and sensory function. Recovery of motor and sensory function after peripheral nerve injury is suboptimal, even after appropriate surgical repair. This is due to the slow rate of axonal elongation during regeneration and atrophic changes that occur in denervated Schwann cells and target muscle with proximal lesions. One way to solve this problem is to accelerate the rate at which the axons regenerate. In this issue of the JCI, Ma and colleagues show that this can be achieved in mice by overexpression of heat shock protein 27, providing hope for enhanced functional recovery in patients after peripheral nerve damage. PMID:21965324
Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal reflex
Jeroen R. Dijkstra; Marcel F. Meek; Peter H. Robinson; Albert Gramsbergen
The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the sciatic nerve and group C consisted
Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies
Juan M Jimenez-Andrade; Monica B Herrera; Joseph R Ghilardi; Marina Vardanyan; Ohannes K Melemedjian; Patrick W Mantyh
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent
Nerve Growth Factor Mediates a Switch in Intracellular Signaling for PGE2-Induced Sensitization of Sensory Neurons from Protein Kinase A to Epac
Vasko, Michael R.; Habashy Malty, Ramy; Guo, Chunlu; Duarte, Djane B.; Zhang, Yihong; Nicol, Grant D.
We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation. PMID:25126967
What Does Functional Testing Tell Us About Optic Nerve Damage?
Pamela A Sample
Information from different regions of the visual field travels through specific bundles of retinal ganglion cell axons. This visual information is disrupted in patients with glaucoma, and the effects can be seen in measurements of the visual field and optic nerve. Typical shapes and sizes of glaucomatous field defects result from damage to these nerve fiber bundles at the level
A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.
Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D
When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2071700
The vestibulocochlear nerve (VIII).
Benoudiba, F; Toulgoat, F; Sarrazin, J-L
The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve. PMID:24095603
TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons
U. Anand; W. R. Otto; P. Facer; N. Zebda; I. Selmer; M. J. Gunthorpe; I. P. Chessell; M. Sinisi; R. Birch; P. Anand
TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17°C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised
Relationships among repetitive behaviors, sensory features, and executive functions in high functioning autism
Brian A. Boyd; Matthew McBee; Tia Holtzclaw; Grace T. Baranek; James W. Bodfish
This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N=61) were compared to healthy, typical controls (N=64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction explained any relationship between the variables. Particular types of repetitive behavior (i.e., stereotypy and compulsions)
Restoration of visual function following optic nerve regeneration in bluegill ~Lepomis macrochirus!
Mensinger, Allen F.
Restoration of visual function following optic nerve regeneration in bluegill ~Lepomis macrochirus ~Lepomis macrochirus! pumpkinseed ~Lepomis gibbosus! hybrid sunfish. Regenerating optic nerve axons! pumpkinseed ~Lepomis gibbosus! hybrid sunfish MICHAEL P. CALLAHAN1,2 and ALLEN F. MENSINGER1 1 Department
Muller, Karra
Patients with large-fiber diabetic sensorimotor polyneuropathy (DPN) can develop altered sensorimotor function. Gait and balance control are regulated, in part, through large sensory nerves innervating muscle spindles. The overall goal...
Sparsity and Compressed Coding in Sensory Systems Victor J. Barranca1,2
Kovacic, Gregor
by a significantly smaller network of ganglion cells before entering the optic nerve. How then is sensory information and transmitted through a wide array of neuronal networks of various sizes and functionalities. Despite
3D multi-channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration.
Dinis, T M; Elia, R; Vidal, G; Dermigny, Q; Denoeud, C; Kaplan, D L; Egles, C; Marin, F
Despite technological advances over the past 25 years, a complete recovery from peripheral nerve injuries remains unsatisfactory today. The autograft is still considered the "gold standard" in clinical practice; however, postoperative complications and limited availability of nerve tissue have motivated the development of alternative approaches. Among them, the development of biomimetic nerve graft substitutes is one of the most promising strategies. In this study, multichanneled silk electrospun conduits bi-functionalized with Nerve Growth Factor (NGF) and Ciliary Neurotropic Factor (CNTF) were fabricated to enhance peripheral nerve regeneration. These bioactive guides consisting of longitudinally oriented channels and aligned nanofibers were designed in order to mimic the fascicular architecture and fibrous extracellular matrix found in native nerve. The simple use of the electrospinning technique followed by a manual manipulation to manufacture these conduits provides tailoring of channel number and diameter size to create perineurium-like structures. Functionalization of the silk fibroin nanofiber did not affect its secondary structure and chemical property. ELISA assays showed the absence of growth factors passive release from the functionalized fibers avoiding the topical accumulation of proteins. In addition, our biomimetic multichanneled functionalized nerve guides displayed a mechanical behavior comparable to that of rat sciatic nerve with an ultimate peak stress of 4.0 ± 0.6 MPa and a corresponding elongation at failure of 156.8 ± 46.7%. Taken together, our results demonstrate for the first time our ability to design and characterize a bi-functionalized nerve conduit consisting of electrospun nanofibers with multichannel oriented and nanofibers aligned for peripheral regeneration. Our bioactive silk tubes thus represent a new and promising technique towards the creation of a biocompatible nerve guidance conduit. PMID:25460402
Assessment of functional recovery of sciatic nerve in rats submitted to low-level laser therapy with different fluences. An experimental study: laser in functional recovery in rats.
Marcolino, Alexandre Marcio; Barbosa, Rafael Inácio; das Neves, Lais Mara Siqueira; Mazzer, Nilton; de Jesus Guirro, Rinaldo Roberto; de Cássia Registro Fonseca, Marisa
Peripheral nerve lesions caused sensory and motor deficits along the distribution of the injured nerve. Numerous researches have been carried out to enhance and/or accelerate the recovery of such lesions. The objective of this study was to assess the functional recovery of sciatic nerve in rats subjected to different fluences of low-level laser therapy (LLLT). Thirty-six animals were randomly divided into four groups: one consisting of sham rats and three others irradiated with progressive fluencies of 10 J/cm(2), 40 J/cm(2) and 80 J/cm(2) of laser AsGaAl (830 nm) for 21 consecutive days. They were evaluated by the Sciatic Functional Index (SFI) method. The crush injury was performed by using a portable device with dead weight of 5,000 g whose load was applied for 10 min. A digital camera was used to record the footprints left on the acrylic track, before surgery and after, on the 7th, 14th, and 21st days. The results also showed that on the 7th day, there was a difference between the groups irradiated with 40 J/cm(2), when compared with the sham group (p?0.05). On the 14th day the groups irradiated with 40 J/cm(2) and 80 J/cm(2) also presented better results when compared with sham, however, on the 21st day, no inter-group difference was found (p?>?0.05). It was possible to observe that the LLLT at fluency of 40 J/cm(2) and 80 J/cm(2) had a positive influence on the acceleration of the functional nerve recovery. PMID:24426674
Effect of skilled and unskilled training on nerve regeneration and functional recovery
Pagnussat, A.S.; Michaelsen, S.M.; Achaval, M.; Ilha, J.; Hermel, E.E.S.; Back, F.P.; Netto, C.A.
The most disabling aspect of human peripheral nerve injuries, the majority of which affect the upper limbs, is the loss of skilled hand movements. Activity-induced morphological and electrophysiological remodeling of the neuromuscular junction has been shown to influence nerve repair and functional recovery. In the current study, we determined the effects of two different treatments on the functional and morphological recovery after median and ulnar nerve injury. Adult Wistar male rats weighing 280 to 330?g at the time of surgery (N = 8-10 animals/group) were submitted to nerve crush and 1 week later began a 3-week course of motor rehabilitation involving either "skilled" (reaching for small food pellets) or "unskilled" (walking on a motorized treadmill) training. During this period, functional recovery was monitored weekly using staircase and cylinder tests. Histological and morphometric nerve analyses were used to assess nerve regeneration at the end of treatment. The functional evaluation demonstrated benefits of both tasks, but found no difference between them (P > 0.05). The unskilled training, however, induced a greater degree of nerve regeneration as evidenced by histological measurement (P < 0.05). These data provide evidence that both of the forelimb training tasks used in this study can accelerate functional recovery following brachial plexus injury. PMID:22584636
A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.
Selvaraj, Deepitha; Gangadharan, Vijayan; Michalski, Christoph W; Kurejova, Martina; Stösser, Sebastian; Srivastava, Kshitij; Schweizerhof, Matthias; Waltenberger, Johannes; Ferrara, Napoleone; Heppenstall, Paul; Shibuya, Masabumi; Augustin, Hellmut G; Kuner, Rohini
Cancer pain is a debilitating disorder and a primary determinant of the poor quality of life. Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies. PMID:26058077
A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain
Selvaraj, Deepitha; Gangadharan, Vijayan; Michalski, Christoph W.; Kurejova, Martina; Stösser, Sebastian; Srivastava, Kshitij; Schweizerhof, Matthias; Waltenberger, Johannes; Ferrara, Napoleone; Heppenstall, Paul; Shibuya, Masabumi; Augustin, Hellmut G.; Kuner, Rohini
Summary Cancer pain is a debilitating disorder and a primary determinant of the poor quality of life. Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies. PMID:26058077
Peripheral nerve regeneration through collagen devices with different in vivo degradation characteristics
Harley, Brendan A. (Brendan Andrew), 1978-
In the United States more than 200,000 people are treated each year for peripheral nerve injuries that require surgery. Functional recovery of motor and sensory capability is limited following autograft, the most common ...
Comparison of the sensory threshold in healthy human volunteers with the sensory nerve response of the rat in vitro hindlimb skin and saphenous nerve preparation on cutaneous electrical stimulation
R. M. R. McAllister; L. A. Urban; A. Dray; P. J. Smith
We report a comparative study of stimulation thresholds of cutaneous fibres of the rat in vitro skin and saphenous nerve preparation with psychophysical measurements of sensibility to cutaneous electrical stimulation in human volunteers. The same clinical diagnostic stimulator and modified skin electrodes were used in both animal and human experiments. Axons were recruited by increasing the stimulus strength, and correlation
Functional identification of sensory mechanisms required for developmental song learning
London, Sarah E; Clayton, David F
A young male zebra finch (Taeniopygia guttata) learns to sing by copying the vocalizations of an older tutor in a process that parallels human speech acquisition. Brain pathways that control song production are well defined, but little is known about the sites and mechanisms of tutor song memorization. Here we test the hypothesis that molecular signaling in a sensory brain area outside of the song system is required for developmental song learning. Using controlled tutoring and a pharmacological inhibitor, we transiently suppressed the extracellular signal–regulated kinase signaling pathway in a portion of the auditory forebrain specifically during tutor song exposure. On maturation, treated birds produced poor copies of tutor song, whereas controls copied the tutor song effectively. Thus the foundation of normal song learning, the formation of a sensory memory of tutor song, requires a conserved molecular pathway in a brain area that is distinct from the circuit for song motor control. PMID:18391944
On sex-related differences in auditory and visual sensory functioning.
Rammsayer, Thomas H; Troche, Stefan J
The present study was designed to elucidate sex-related differences in two basic auditory and one basic visual aspect of sensory functioning, namely sensory discrimination of pitch, loudness, and brightness. Although these three aspects of sensory functioning are of vital importance in everyday life, little is known about whether men and women differ from each other in these sensory functions. Participants were 100 male and 100 female volunteers ranging in age from 18 to 30 years. Since sensory sensitivity may be positively related to individual levels of intelligence and musical experience, measures of psychometric intelligence and musical background were also obtained. Reliably better performance for men compared to women was found for pitch and loudness, but not for brightness discrimination. Furthermore, performance on loudness discrimination was positively related to psychometric intelligence, while pitch discrimination was positively related to both psychometric intelligence and levels of musical training. Additional regression analyses revealed that each of three predictor variables (sex, psychometric intelligence, and musical training) accounted for a statistically significant portion of unique variance in pitch discrimination. With regard to loudness discrimination, regression analysis yielded a statistically significant portion of unique variance for sex as a predictor variable, whereas psychometric intelligence just failed to reach statistical significance. The potential influence of sex hormones on sex-related differences in sensory functions is discussed. PMID:22183583
Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury
Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu
Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. PMID:25821803
Ketoprofen combined with artery graft entubulization improves functional recovery of transected peripheral nerves.
Mohammadi, Rahim; Mehrtash, Moein; Nikonam, Nima; Mehrtash, Moied; Amini, Keyvan
The objective was to assess the local effect of ketoprofen on sciatic nerve regeneration and functional recovery. Eighty healthy male white Wistar rats were randomized into four experimental groups of 20 animals each: In the transected group (TC), the left sciatic nerve was transected and nerve cut ends were fixed in the adjacent muscle. In the treatment group the defect was bridged using an artery graft (AG/Keto) filled with 10 microliter ketoprofen (0.1 mg/kg). In the artery graft group (AG), the graft was filled with phosphated-buffer saline alone. In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. Each group was subdivided into four subgroups of five animals each and regenerated nerve fibres were studied at 4, 8, 12 and 16 weeks post operation. Behavioural testing, sciatic nerve functional study, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in AG/Keto than in AG group (p < 0.05). Immunohistochemical study clearly showed more positive location of reactions to S-100 in AG/Keto than in AG group. When loaded in an artery graft, ketoprofen improved functional recovery and morphometric indices of the sciatic nerve. Local usage of this easily accessible therapeutic medicine is cost saving and avoids the problems associated with systemic administration. PMID:23932540
Conventional and Functional MR Imaging of Peripheral Nerve Sheath Tumors: Initial Experience
Demehri, S.; Belzberg, A.; Blakeley, J.; Fayad, L.M.
BACKGROUND AND PURPOSE Differentiating benign from malignant peripheral nerve sheath tumors can be very challenging using conventional MR imaging. Our aim was to test the hypothesis that conventional and functional MR imaging can accurately diagnose malignancy in patients with indeterminate peripheral nerve sheath tumors. MATERIALS AND METHODS This institutional review board–approved, Health Insurance Portability and Accountability Act–compliant study retrospectively reviewed 61 consecutive patients with 80 indeterminate peripheral nerve sheath tumors. Of these, 31 histologically proved peripheral nerve sheath tumors imaged with conventional (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted sequences) and functional MR imaging (DWI/apparent diffusion coefficient mapping, dynamic contrast-enhanced MR imaging) were included. Two observers independently assessed anatomic (size, morphology, signal) and functional (ADC values, early arterial enhancement by dynamic contrast-enhanced MR) features to determine interobserver agreement. The accuracy of MR imaging for differentiating malignant from benign was also determined by receiver operating characteristic analysis. RESULTS Of 31 peripheral nerve sheath tumors, there were 9 malignant (9%) and 22 benign ones (81%). With anatomic sequences, average tumor diameter (6.3 ± 1.8 versus 3.9 ± 2.3 mm, P = .009), ill-defined/infiltrative margins (77% versus 32%; P = .04), and the presence of peritumoral edema (66% versus 23%, P = .01) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. With functional sequences, minimum ADC (0.47 ± 0.32 × 10?3 mm2/s versus 1.08 ± 0.26 × 10?3 mm2/s; P [H11021] .0001) and the presence of early arterial enhancement (50% versus 11%; P = .03) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. The minimum ADC (area under receiver operating characteristic curve was 0.89; 95% confidence interval, 0.73– 0.97) and the average tumor diameter (area under the curve = 0.8; 95% CI, 0.66 – 0.94) were accurate in differentiating malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors. With threshold values for minimum ADC ? 1.0 × 10?3 mm2/s and an average diameter of ?4.2 cm, malignancy could be diagnosed with 100% sensitivity (95% CI, 66.4%–100%). CONCLUSIONS Average tumor diameter and minimum ADC values are potentially important parameters that may be used to distinguish malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors. PMID:24763412
Stem cell salvage of injured peripheral nerve.
Grimoldi, Nadia; Colleoni, Federica; Tiberio, Francesca; Vetrano, Ignazio G; Cappellari, Alberto; Costa, Antonella; Belicchi, Marzia; Razini, Paola; Giordano, Rosaria; Spagnoli, Diego; Pluderi, Mauro; Gatti, Stefano; Morbin, Michela; Gaini, Sergio M; Rebulla, Paolo; Bresolin, Nereo; Torrente, Yvan
We previously developed a collagen tube filled with autologous skin-derived stem cells (SDSCs) for bridging long rat sciatic nerve gaps. Here we present a case report describing a compassionate use of this graft for repairing the polyinjured motor and sensory nerves of the upper arms of a patient. Preclinical assessment was performed with collagen/SDSC implantation in rats after sectioning the sciatic nerve. For the patient, during the 3-year follow-up period, functional recovery of injured median and ulnar nerves was assessed by pinch gauge test and static two-point discrimination and touch test with monofilaments, along with electrophysiological and MRI examinations. Preclinical experiments in rats revealed rescue of sciatic nerve and no side effects of patient-derived SDSC transplantation (30 and 180 days of treatment). In the patient treatment, motor and sensory functions of the median nerve demonstrated ongoing recovery postimplantation during the follow-up period. The results indicate that the collagen/SDSC artificial nerve graft could be used for surgical repair of larger defects in major lesions of peripheral nerves, increasing patient quality of life by saving the upper arms from amputation. PMID:24268028
Concordance between epidermal nerve fiber density and sensory examination in patients with symptoms of idiopathic small fiber neuropathy
David Walk; Gwen Wendelschafer-Crabb; Cynthia Davey; William R. Kennedy
Quantitation of epidermal nerve fiber (ENF) density is an objective diagnostic test of small fiber neuropathy (SFN). For a diagnostic test to be clinically useful it should correspond well with clinically meaningful physical findings. We performed a retrospective analysis of the concordance between foot ENF density and clinical findings in all patients seen at our institution with possible idiopathic SFN
Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies
Grinsell, D.; Keating, C. P.
Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery. PMID:25276813
Retrospective study of facial nerve function following temporomandibular joint arthroplasty using the endaural approach.
Liu, Frederick; Giannakopoulos, Helen; Quinn, Peter D; Granquist, Eric J
The aim of this retrospective case-control study is to evaluate the incidence of facial nerve injury associated with temporomandibular joint (TMJ) arthroplasty using the endaural approach for the treatment of TMJ pathology. The sample consisted of 36 consecutive patients who underwent TMJ arthroplasty. A total of 39 approaches were performed through an endaural incision. Patients undergoing total joint replacement and/or with preexisting facial nerve dysfunction were excluded from the study. Five patients were lost to follow-up and were excluded from the study. Facial nerve function of all patients was clinically evaluated by resident physicians preoperatively, postoperatively, and at follow-up appointments. Facial nerve injury was determined to have occurred if the patient was unable to raise the eyebrow or wrinkle the forehead (temporalis branch), completely close the eyelids (zygomatic branch), or frown (marginal mandibular branch). Twenty-one of the 36 patients or 22 of the 39 approaches showed signs of facial nerve dysfunction following TMJ arthroplasty. This included 12 of the 21 patients who had undergone previous TMJ surgery. The most common facial nerve branch injured was the temporal branch, which was dysfunctional in all patients either as the only branch injured or in combination with other branches. By the 18th postoperative month, normal function had returned in 19 of the 22 TMJ approaches. Three of the 22 TMJ approaches resulted in persistent signs of facial nerve weakness 6 months after the surgery. This epidemiological study revealed a low incidence of permanent facial nerve dysfunction. A high incidence of temporary facial nerve dysfunction was seen with TMJ arthroplasty using the endaural approach. Current literature reveals that the incidence of facial nerve injury associated with open TMJ surgery ranges from 12.5 to 32%. The temporal branch of the facial nerve was most commonly affected, followed by 4 of the 22 approaches with temporary zygomatic branch weakness. Having undergone previous TMJ surgery did not increase the incidence of facial nerve injury using the endaural approach. This information is important for patients and surgeons in the postoperative period, as a majority of patients will experience recovery of nerve function. PMID:26000077
Kv7.2 regulates the function of peripheral sensory neurons.
King, Chih H; Lancaster, Eric; Salomon, Daniela; Peles, Elior; Scherer, Steven S
The Kv7 (KCNQ) family of voltage-gated K(+) channels regulates cellular excitability. The functional role of Kv7.2 has been hampered by the lack of a viable Kcnq2-null animal model. In this study, we generated homozygous Kcnq2-null sensory neurons using the Cre-Lox system; in these mice, Kv7.2 expression is absent in the peripheral sensory neurons, whereas the expression of other molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is not altered. The conditional Kcnq2-null animals exhibit normal motor performance but have increased thermal hyperalgesia and mechanical allodynia. Whole-cell patch recording technique demonstrates that Kcnq2-null sensory neurons have increased excitability and reduced spike frequency adaptation. Taken together, our results suggest that the loss of Kv7.2 activity increases the excitability of primary sensory neurons. PMID:24687876
Imaging of temperature dependent hemodynamics in the rat sciatic nerve by functional photoacoustic microscopy
Background Vascular hemodynamics is central to the regulation of neuro-metabolism and plays important roles in peripheral nerves diseases and their prevention. However, at present there are only a few techniques capable of directly measuring peripheral nerve vascular hemodynamics. Method Here, we investigate the use of dark-field functional photoacoustic microscopy (fPAM) for intrinsic visualizing of the relative hemodynamics of the rat sciatic nerve in response to localized temperature modulation (i.e., cooling and rewarming). Results and conclusion Our main results show that the relative functional total hemoglobin concentration (HbT) is more significantly correlated with localized temperature changes than the hemoglobin oxygen saturation (SO2) changes in the sciatic nerve. Our study also indicates that the relative HbT changes are better markers of neuronal activation than SO2 during nerve temperature changes. Our results show that fPAM is a promising candidate for in vivo imaging of peripheral nerve hemodynamics without the use of contrast agents. Additionally, this technique may shed light on the neuroprotective effect of hypothermia on peripheral nerves by visualizing their intrinsic hemodynamics. PMID:24245952
Functional stimulation of graft nerves has minor effects on insulin release from transplanted rat pancreatic islets
Kampf, Caroline; Källskog, Örjan
Introduction. Morphological evidence for reinnervation of pancreatic islet grafts is plentiful. However, to what extent intra-graft nerves influence the endocrine functions of the islet transplant is largely unknown. We therefore aimed to directly stimulate nerves leading to islet grafts with electrodes and measure insulin secretion in response to this. Methods. We implanted syngeneic islets under the renal capsule of rats, and examined them 1 or 7–9 months later. In anesthetized rats blood samples were collected from the renal vein and femoral artery, respectively, during electrode stimulation of the nerves leading to the islet grafts. Results. As expected, nerve stimulation decreased renal blood flow. However, serum insulin concentrations in samples derived from the renal vein or femoral artery changed in concert with one another, both during normoglycemia and acute hyperglycemia. Conclusion. Reinnervation which occurs after islet transplantation under the renal capsule has minor effects on graft endocrine function. PMID:23977866
Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor
Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.
Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607
Altered rectal sensory response induced by balloon distention in patients with functional abdominal pain syndrome
Tsukasa Nozu; Miwako Kudaira
BACKGROUND: Functional abdominal pain syndrome (FAPS) has chronic unexplained abdominal pain and is similar to the psychiatric diagnosis of somatoform pain disorder. A patient with irritable bowel syndrome (IBS) also has chronic unexplained abdominal pain, and rectal hypersensitivity is observed in a majority of the patients. However, no reports have evaluated the visceral sensory function of FAPS precisely. We aimed
Nerve and Nerve Root Biomechanics
Kristen J. Nicholson; Beth A. Winkelstein
\\u000a Together, the relationship between the mechanical response of neural tissues and the related mechanisms of injury provide\\u000a a foundation for defining relevant thresholds for injury. The nerves and nerve roots are biologic structures with specific\\u000a and important functions, and whose response to mechanical loading can have immediate, long-lasting and widespread consequences.\\u000a In particular, when nerves or nerve roots are mechanically
Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration
Lavasani, Mitra; Thompson, Seth D.; Pollett, Jonathan B.; Usas, Arvydas; Lu, Aiping; Stolz, Donna B.; Clark, Katherine A.; Sun, Bin; Péault, Bruno; Huard, Johnny
Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating Schwann cells. Engraftment of hMDSPCs into the area of the damaged nerve promoted axonal regeneration, which led to functional recovery as measured by sustained gait improvement. Furthermore, no adverse effects were observed in these animals up to 18 months after transplantation. Following hMDSPC therapy, gastrocnemius muscles from mice exhibited substantially less muscle atrophy, an increase in muscle mass after denervation, and reorganization of motor endplates at the postsynaptic sites compared with those from PBS-treated mice. Evaluation of nerve defects in animals transplanted with vehicle-only or myoblast-like cells did not reveal histological or functional recovery. These data demonstrate the efficacy of hMDSPC-based therapy for peripheral nerve injury and suggest that hMDSPC transplantation has potential to be translated for use in human neuropathies. PMID:24642464
Recovery of laryngeal function after intraoperative injury to the recurrent laryngeal nerve
Hydman, Jonas; Svensson, Mikael
Loss of function in the recurrent laryngeal nerve (RLN) during thyroid/parathyroid surgery, despite a macroscopically intact nerve, is a challenge which highlights the sensitivity and complexity of laryngeal innervation. Furthermore, the uncertain prognosis stresses a lack of capability to diagnose the reason behind the impaired function. There is a great deal of literature considering risk factors, surgical technique and mechanisms outside the nerve affecting the incidence of RLN paresis during surgery. To be able to prognosticate recovery in cases of laryngeal dysfunction and voice changes after thyroid surgery, the surgeon would first need to define the presence, location, and type of laryngeal nerve injury. There is little data describing the events within the nerve and the neurobiological reasons for the impaired function related to potential recovery and prognosis. In addition, very little data has been presented in order to clarify any differences between the transient and permanent injury of the RLN. This review aims, from an anatomical and neurobiological perspective, to provide an update on the current understandings of surgically-induced injury to the laryngeal nerves. PMID:25713777
Fibre function and perception during cutaneous nerve block.
Mackenzie, R A; Burke, D; Skuse, N F; Lethlean, A K
In awake human subjects, neural responses in radial nerves to electrical stimulation were recorded with intrafascicular tungsten microelectrodes. Changes in the activity of individual fibre groups during blocking procedures were recorded and correlated with simultaneous alterations in the perception of standardized stimuli. Light touch sensibility in hairy skin appeared to depend on the integrity of A-beta-gamma fibres, cold and pinprick on A-delta fibres, and warmth and dull pain on C fibres. PMID:1185225
Ultrastructural Changes in Spinal Motoneurons and Locomotor Functional Study after Sciatic Nerve Repair in Conduit Tube
Delaviz, Hamdollah; Faghihi, Abolfazel; Mohamadi, Jamshid; Roozbehi, Amrollah
Objective(s) Motor deficit and neuron degeneration is seen after nerve transection. The aim of this study is to determine whether a poled polyvinelidene fluoride (PVDF) tube with other supportive strategies can protect the neuronal morphology and motor function after sciatic nerve transaction in rats. Materials and Methods After transection of the left sciatic nerve in 60 male Wistar rats (200-250 g), the epineural group was sutured end to end. In the autograft rats, a 10 mm piece of sciatic nerve was rotated 180 °C and sutured back into the nerve gap. In the nerve guidance channel (NGC) group, polarized piezoelectric PVDF tube containing NGF and collagen gel was sutured in the gap. In control group sciatic nerve was removed (10 mm) without repair. After one, four and eight weeks, the L4-L6 spinal cord segment was removed for histological study using transmission electron microscope. Functional outcome was assessed using the Basso, Bresnahan and Beattie (BBB) locomotor scale at both four and eight weeks after the lesion. Results Chromatin condensation was seen after 4 weeks in the repair groups. Cell membrane shrinkage and mitochondrial degeneration was observed after 4 and 8 weeks respectively, in the autografted and NGC rats. In the control group, chromatin condensation, cell membrane shrinkage with mitochondrial degeneration and vacuolization of perikaryon was seen after 1, 4 and 8 weeks, respectively. At 56 days, the functional recovery of the epineural rats significantly increased in comparison to the other groups (P< 0.05). Conclusion The epineural suture has more efficacies, and NGC may be used as a proper substitute for autograft in nerve injury. PMID:23492837
Nerve growth factor acts through the TrkA receptor to protect sensory neurons from the damaging effects of the HIV-1 viral protein, Vpr
Webber, Christine A.; Salame, Jihan; Luu, Gia-Linh S.; Acharjee, Shaona; Ruangkittisakul, Araya; Martinez, Jose A.; Jalali, Hanieh; Watts, Russell; Ballanyi, Klaus; Guo, Gui Fang; Zochodne, Douglas W.; Power, Christopher
Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF responsive fibers. Herein, the actions of NGF were investigated in our Vpr model of DSP and we demonstrated that NGF significantly protected sensory neurons from the effects of Vpr. Footpads of immunodeficient Vpr transgenic (vpr/RAG1?/?) mice displayed allodynia (p<0.05), diminished epidermal innervation (p<0.01) and reduced NGF mRNA expression (p<0.001) compared to immunodeficient (wildtype/RAG1?/?) littermate control mice. Compartmented cultures confirmed recombinant Vpr exposure to the DRG neuronal perikarya decreased distal neurite extension (p<0.01), whereas NGF exposure at these distal axons protected the DRG neurons from the Vpr-induced effect on their cell bodies. NGF prevented Vpr-induced attenuation of the phosphorylated glycogen synthase-3 axon extension pathway and tropomyosin related kinase A (TrkA) receptor expression in DRG neurons (p<0.05) and it directly counteracted the cytosolic calcium burst caused by Vpr exposure to DRG neurons (p<0.01). TrkA receptor antagonists indicated that NGF acted through the TrkA receptor to block the Vpr-mediated decrease in axon outgrowth in neonatal and adult rat and fetal human DRG neurons (p<0.05). Similarly, inhibiting the lower affinity NGF receptor, p75, blocked Vpr's effect on DRG neurons. Overall, NGF/TrkA signalling or p75 receptor inhibition protects somatic sensory neurons exposed to Vpr, thus laying the groundwork for potential therapeutic options for HIV/AIDS patients suffering from DSP. PMID:23912036
Neuropeptides in insect sensory neurones: tachykinin-, FMRFamide- and allatotropin-related peptides in terminals of locust thoracic sensory afferents.
Persson, M G; Nässel, D R
Sensory afferents in the thoracic ganglia of the locust Locusta migratoria were labelled with antisera to different neuropeptides: locustatachykinins, FMRFamide and allatotropin. The locustatachykinin-immunoreactive (LTKIR) sensory fibres were derived from the legs and entered the ventral sensory neuropil of each of the thoracic ganglia via nerve 5. In the thoracic neuropil, the LTKIR sensory fibres formed a distinct plexus of terminations ventrally in the ipsilateral hemisphere. The peripheral cell bodies of the sensory neurones could not be revealed, but lesion experiments indicated that origin of the LTKIR fibres was the tarsus of each leg. Possibly the thin fibres are from tarsal chemoreceptors. Double labelling immunocytochemistry revealed that all the LTKIR sensory fibres contained colocalized FMRFamide immunoreactivity. A larger population of sensory fibres reacted with antiserum to moth (Manduca sexta) allatotropin. By means of double labelling immunocytochemistry, we could show that the LTKIR fibres constituted a subpopulation of the larger set of allatotropin-like immunoreactive fibres. Thus some sensory fibres may contain colocalized peptides related to locustatachykinins, FMRFamide-related peptide(s) and allatotropin-like peptide. A separate non-overlapping small set of sensory fibres in nerve 5 reacted with an antiserum to serotonin. Sensory fibres of the other nerves of the ventral nerve cord, including the abdominal ganglia, did not react with the peptide antisera. Since acetylcholine is the likely primary neurotransmitter of insect sensory fibres, it is possible that the peptides and serotonin are colocalized with this transmitter and serve modulatory functions in a subset of the leg afferents. PMID:9878709
Prevention and reversal of motor and sensory peripheral nerve conduction abnormalities in streptozotocin-diabetic rats by the prostacyclin analogue iloprost
M. A. Cotter; K. C. Dines; N. E. Cameron
The effects of the prostacyclin analogue iloprost on nerve function were examined in streptozotocin-diabetic rats. Rats were treated either with iloprost from induction of diabetes over 2 months in a preventive experiment, or for 1 month following a 1 month untreated period of diabetes in a reversal experiment. One and 2 months untreated diabetic control, non-diabetic control, and iloprost-treated non-diabetic
Asymptomatic small fiber neuropathy in diabetes mellitus: investigations with intraepidermal nerve fiber density, quantitative sensory testing and laser-evoked potentials
Michael Ragé; Nathalie Van Acker; Michiel W. M. Knaapen; Maarten Timmers; Johannes Streffer; Michel P. Hermans; Christian Sindic; Theo Meert; Léon Plaghki
This study aimed at evaluating the performance of a battery of morphological and functional tests for the assessment of small\\u000a nerve fiber loss in asymptomatic diabetic neuropathy (DNP). Patients diagnosed for ?10 years with type 1 (n = 10) or type 2 (n = 13) diabetes mellitus (DM) without conventional symptoms or signs of DNP were recruited and compared with healthy controls\\u000a (n = 18) and patients
Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas.
Sellers, Kristin K; Bennett, Davis V; Hutt, Axel; Williams, James H; Fröhlich, Flavio
During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839
An implantable wireless system for muscle afferent recording from the sciatic nerve during functional electrical stimulation.
Song, Kang-Il; Shon, Ahnsei; Chu, Jun-Uk; Choi, Kuiwon; Hwang, Dosik; Youn, Inchan
An implantable wireless system was developed for recording muscle afferent activity and stimulating peripheral nerves with cuff electrodes. The proposed system was fabricated into the nerve cuff electrode, neural amplifier, neural stimulator, and wireless communication system with battery power. The nerve cuff electrode and neural amplifier were designed to improve the signal-to-interference ratio and signal-to-noise ratio. The wireless communication system was designed based on the medical implant communication service regulations to be suitable for implantation. The main function of this system was to extract muscle afferent activity from peripheral nerve during functional electrical stimulation. The cuff electrodes were chronically implanted on the sciatic nerve for recording and on the tibial and peroneal nerves for stimulation. When the extension and flexion movements of ankle joint were elicited from alternative electrical stimuli, the corresponding neural signals and ankle angles were recorded simultaneously. The muscle afferent activity was then extracted from the recorded neural signal through a simple blanking process. The experimental results showed that the ankle movements could be detected from the extracted muscle afferent activity. PMID:24110511
Misdirection of regenerating axons and functional recovery following sciatic nerve injury in rats.
Hamilton, Shirley K; Hinkle, Marcus L; Nicolini, Jennifer; Rambo, Lindsay N; Rexwinkle, April M; Rose, Sam J; Sabatier, Manning J; Backus, Deborah; English, Arthur W
Poor functional recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery. PMID:21120925
Siao, Peter; Cros, Didier P
Quantitative sensory testing is a reliable way of assessing large and small sensory nerve fiber function. Sensory deficits may be quantified and the data used in parametric statistical analysis in research studies and drug trials. It is an important addition to the neurophysiologic armamentarium, because conventional sensory nerve conduction tests only the large fibers. QST is a psychophysical test and lacks the objectivity of NCS. The results are subject to changes owing to distraction, boredom, mental fatigue, drowsiness, or confusion. When patients are consciously or unconsciously biased toward an abnormal QST result, no psychophysical testing can reliably distinguish these patients from those with organic disease. QST tests the integrity of the entire sensory neuraxis and is of no localizing value. Dysfunction of the peripheral nerves or central nervous system may give rise to abnormalities in QST. As is true for other neurophysiologic tests, QST results should always be interpreted in light of the patient's clinical presentation. Quantitative sensory testing has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. Because longitudinal QST studies of patients in drug trials are usually performed over a period of several months to a few years, reproducibility studies on the placebo-control group should be included. For individual patients, more studies are needed to determine the maximum allowable difference between two QSTs that can be attributed to experimental error. The reproducibility of thermal thresholds may not be as good as that of vibration threshold. Different commercially available QST instruments have different specifications (thermode size, stimulus characteristics), testing protocols, algorithms, and normal values. Only QST instruments and their corresponding methodologies that have been shown to be reproducible should be used for research and patient care. The data in the literature do not allow conclusions regarding the superiority of any QST instruments. The future of QST is promising; however, many factors can affect QST results. As is true for other neurophysiologic tests, QST is susceptible to many extraneous factors and to misuse when not properly interpreted by the clinician. PMID:12795516
Normal nerve conduction velocity and vibrotactile perception thresholds in computer users
Helena Sandén; Micael Edblom; Anna Ekman; Artur Tenenbaum; B Gunnar Wallin; Mats Hagberg
Objectives: A literature report described significantly raised vibration threshold within the territory of the median nerve in a group of office workers and concluded that the results indicated a change in the function of large sensory fibres. The aim of the present cross-sectional study was to compare vibrotactile perception thresholds and nerve conduction measurements in the upper extremity between female
Increase in NGF content and nerve fiber sprouting in human allergic contact eczema
Ilka Kinkelin; Sandra Mötzing; Martin Koltzenburg; Eva-Bettina Bröcker
There is increasing evidence for an intimate interaction of the skin and the nervous system. As known from animal studies, nerve growth factor (NGF) is essential for the innervation density and functional properties of sensory neurons of the skin during embryogenesis and in adulthood, and possibly during cutaneous inflammation. This study examined NGF content and sprouting of nerves during the
Importance of Tissue Morphology Relative to Patient Reports of Symptoms and Functional Limitations Resulting From Median Nerve Pathology
Evans, Kevin D.; Li, Xiaobai; Sommerich, Carolyn M.; Case-Smith, Jane
Significant data exist for the personal, environmental, and occupational risk factors for carpal tunnel syndrome. Few data, however, explain the interrelationship of tissue morphology to these factors among patients with clinical presentation of median nerve pathology. Therefore, our primary objective was to examine the relationship of various risk factors that may be predictive of subjective reports of symptoms or functional deficits accounting for median nerve morphology. Using diagnostic ultrasonography, we observed real-time median nerve morphology among 88 participants with varying reports of symptoms or functional limitations resulting from median nerve pathology. Body mass index, educational level, and nerve morphology were the primary predictive factors. Monitoring median nerve morphology with ultrasonography may provide valuable information for clinicians treating patients with symptoms of median nerve pathology. Sonographic measurements may be a useful clinical tool for improving treatment planning and provision, documenting patient status, or measuring clinical outcomes of prevention and rehabilitation interventions. PMID:23245784
Free vascularized deep peroneal nerve grafts.
Koshima, I; Okumoto, K; Umeda, N; Moriguchi, T; Ishii, R; Nakayama, Y
An ideal donor site for vascularized nerve grafts should have a constant anatomy, minimal functional loss after the nerve has been sacrificed, and a dependable blood supply parallel to the nerve over a relatively long distance. Creating a pedicle for a free vascularized deep peroneal nerve graft with the anterior tibial vessels seems to be a most suitable method for repairing long nerve gaps of over 20 cm and digital nerve defects with severe finger damage. Applications of this nerve graft to digital nerve losses with severely scarred beds created by avulsion injury, and two-stage reconstruction in some partial brachial plexus palsies (free vascularized nerve graft in the first stage and free vascularized muscle graft in the second stage) are well indicated. Advantages of this technique are: (1) A long nerve graft (up to 25 cm) can be obtained, and anomalies are rare (the nerve is absent in only 4 percent of cases). (2) The caliber of the vascular pedicle is large (approximately equal to 3 mm). (3) The nerve has a sufficient blood supply from the collateral blood vessels. (4) The graft can be easily obtained in the supine position. (5) A monitoring skin flap, based on the inferior lateral peroneal artery, can be attached to the nerve graft. (6) Sensory loss resulting from the sacrifice of the nerve covers a minimal area. (7) A donor scar on the anterior aspect of the lower leg is more acceptable than one on the posterior aspect because of less movement in walking. Disadvantages of this technique are: (1) Sacrifice of the large vessels in the lower leg may result in circulatory complications in the donor foot; to avoid this problem, preoperative angiography is recommended. (2) The donor scar is in an exposed area in female patients. (3) There may be temporary postoperative edema and disability in the donor leg. PMID:8726331
Augmented mechanical response of muscle thin-fiber sensory receptors recorded from rat muscle-nerve preparations in vitro after eccentric contraction.
Taguchi, Toru; Sato, Jun; Mizumura, Kazue
Unaccustomed strenuous exercise, especially that from eccentric muscular work, often causes muscle tenderness, which is a kind of mechanical hyperalgesia. We developed an animal model of delayed-onset muscle soreness (DOMS) from eccentric muscular contraction (ECC) in rats and demonstrated the existence of muscle tenderness by means of behavioral pain tests and c-Fos protein expression in the spinal dorsal horn. The purpose of the present study was to examine whether the sensitivities of muscle thin-fiber sensory receptors to mechanical, chemical, and thermal stimuli were altered after repetitive ECC in a rat model of DOMS. ECC was caused in the animals by electrical stimulation of the common peroneal nerve innervating the extensor digitorum longus muscle (EDL) while the muscle was being stretched. Activities of single thin-fiber receptors (sensitive to pressure but insensitive to stretch, with conduction velocity slower than 2.0 m/s) were recorded from muscle (EDL)-nerve preparations in vitro 2 days after ECC when mechanical hyperalgesia was at its peak. The mechanical threshold of thin-fiber receptors was found to be very much lower in the ECC preparations than in the nontreated control (CTR) [median 65.4 mN (interquartile range [IQR]; 46.6-122.0 mN) in the CTR preparation vs. 38.2 mN (IQR; 26.8-55.8 mN) in the ECC, P < 0.001]. In addition, the total number of evoked discharges during a ramp mechanical stimulus, taken as an index of the magnitude of the mechanical response, nearly doubled in the ECC preparations compared with the CTR [24.7 spikes (IQR; 14.2-37.1 spikes) in the CTR preparation vs. 54.2 spikes (IQR; 24.3-89.0 spikes) in the ECC, P < 0.001]. In contrast, the numbers of discharges induced by chemical (pH 5.5, lactic acid, adenosine triphosphate, and bradykinin) and thermal (cold and heat) stimuli were not different between the two preparations. These results suggest that augmentation of the mechanical response in muscle thin-fiber sensory receptors might be related to the muscle tenderness in DOMS after ECC. PMID:16160095
Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways
Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G
AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS: We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. RESULTS: Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 ?g/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION: GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves. PMID:16425415
Strategies to promote recovery of cavernous nerve function after radical prostatectomy
Arthur L. Burnett
While the application of penile autonomic nerve-sparing techniques during radical prostatectomy for clinically localized prostate cancer has improved erection recovery rates after surgery, many men still experience delayed or incomplete recovery of erectile function. In recognition of neuropathy as a likely basis for erectile dysfunction after radical prostatectomy, investigators have begun exploring new strategies to promote the functional recovery of
Sensoric Protection after Median Nerve Injury: Babysitter-Procedure Prevents Muscular Atrophy and Improves Neuronal Recovery
Beck-Broichsitter, Benedicta E.; Becker, Stephan T.; Lamia, Androniki; Fregnan, Federica; Sinis, Nektarios
The babysitter-procedure might offer an alternative when nerve reconstruction is delayed in order to overcome muscular atrophy due to denervation. In this study we aimed to show that a sensomotoric babysitter-procedure after median nerve injury is capable of preserving irreversible muscular atrophy. The median nerve of 20 female Wistar rats was denervated. 10 animals received a sensory protection with the N. cutaneous brachii. After six weeks the median nerve was reconstructed by autologous nerve grafting from the contralateral median nerve in the babysitter and the control groups. Grasping tests measured functional recovery over 15 weeks. At the end of the observation period the weight of the flexor digitorum sublimis muscle was determined. The median nerve was excised for histological examinations. Muscle weight (P < 0.0001) was significantly superior in the babysitter group compared to the control group at the end of the study. The histological evaluation revealed a significantly higher diameter of axons (P = 0.0194), nerve fiber (P = 0.0409), and nerve surface (P = 0.0184) in the babysitter group. We conclude that sensory protection of a motor nerve is capable of preserving muscule weight and we may presume that metabolism of the sensory nerve was sufficient to keep the target muscle's weight and vitality. PMID:25133176
Functional Analysis of Aberrant Behavior Maintained by Automatic Reinforcement: Assessments of Specific Sensory Reinforcers.
ERIC Educational Resources Information Center
Patel, Meeta R.; Carr, James E.; Kim, Christine; Robles, Adel; Eastridge, Dixie
A study developed a systematic functional assessment package to reduce the stereotypy and self-injurious behaviors maintained by nonsocial reinforcement in two individuals with mental retardation. Differential reinforcement of zero rates of responding (DRO) procedures using stimuli within the targeted sensory classes were successful in eliminated…
2,4-Dithiobiuret exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. he present study compares the effects of DTB on sensory and motor function in rats. dult male Long-Evans hooded rats were exposed to saline, ...
Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.
Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru
This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables. PMID:25002406
Thalamic cholinergic innervation and postural sensory integration function in Parkinson's disease.
Müller, Martijn L T M; Albin, Roger L; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J H; Frey, Kirk A; Bohnen, Nicolaas I
The pathophysiology of postural instability in Parkinson's disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in Parkinson's disease. Our aim was to investigate the relationship of cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic denervation, on postural sensory integration function in Parkinson's disease. We studied 124 subjects with Parkinson's disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent (11)C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and (11)C-methylpiperidin-4-yl propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1-3 and 5, respectively. Regression analysis of the Conditions 1-3 postural sway-related factor [R(2)adj = 0.123, F(5,109) = 4.2, P = 0.002] showed that decreased thalamic cholinergic innervation was associated with increased centre of pressure sway speed (? = -0.389, t = -3.4, P = 0.001) while controlling for covariate effects of cognitive capacity and parkinsonian motor impairments. There was no significant effect of cortical cholinergic terminal deficits or striatal dopaminergic terminal deficits. This effect could only be found for the subjects with Parkinson's disease. We conclude that postural sensory integration function of subjects with Parkinson's disease is modulated by pedunculopontine nucleus-thalamic but not cortical cholinergic innervation. Impaired integrity of pedunculopontine nucleus cholinergic neurons and their thalamic efferents play a role in postural control in patients with Parkinson's disease, possibly by participating in integration of multimodal sensory input information. PMID:24056537
Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation.
Patel, Yogi A; Butera, Robert J
Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5-70 kHz and amplitudes of 0.1-3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function. PMID:25878155
Model-based analysis and design of nerve cuff electrodes for restoring bladder function by selective stimulation of the pudendal nerve
NASA Astrophysics Data System (ADS)
Kent, Alexander R.; Grill, Warren M.
Objective. Electrical stimulation of the pudendal nerve (PN) is being developed as a means to restore bladder function in persons with spinal cord injury. A single nerve cuff electrode placed on the proximal PN trunk may enable selective stimulation of distinct fascicles to maintain continence or evoke micturition. The objective of this study was to design a nerve cuff that enabled selective stimulation of the PN. Approach. We evaluated the performance of both flat interface nerve electrode (FINE) cuff and round cuff designs, with a range of FINE cuff heights and number of contacts, as well as multiple contact orientations. This analysis was performed using a computational model, in which the nerve and fascicle cross-sectional positions from five human PN trunks were systematically reshaped within the nerve cuff. These cross-sections were used to create finite element models, with electric potentials calculated and applied to a cable model of a myelinated axon to evaluate stimulation selectivity for different PN targets. Subsequently, the model was coupled to a genetic algorithm (GA) to identify solutions that used multiple contact activation to maximize selectivity and minimize total stimulation voltage. Main results. Simulations did not identify any significant differences in selectivity between FINE and round cuffs, although the latter required smaller stimulation voltages for target activation due to preserved localization of targeted fascicle groups. Further, it was found that a ten contact nerve cuff generated sufficient selectivity for all PN targets, with the degree of selectivity dependent on the relative position of the target within the nerve. The GA identified solutions that increased fitness by 0.7-45.5% over single contact activation by decreasing stimulation of non-targeted fascicles. Significance. This study suggests that using an optimal nerve cuff design and multiple contact activation could enable selective stimulation of the human PN trunk for restoration of bladder function.
A Novel Internal Fixator Device for Peripheral Nerve Regeneration
Chuang, Ting-Hsien; Wilson, Robin E.; Love, James M.; Fisher, John P.
Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension—traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration. PMID:23102114
Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation
Aldrich, Benjamin T.; Frakes, Eli P.; Kasuya, Junko; Hammond, Donna L.; Kitamoto, Toshihiro
Chronic neuropathic pain caused by peripheral nerve injury is associated with global changes in gene expression in damaged neurons. To understand the molecular mechanisms underlying neuropathic pain, it is essential to elucidate how nerve injury alters gene expression and how the change contributes to the development and maintenance of chronic pain. MicroRNAs are non-protein-coding RNA molecules that regulate gene expression in a wide variety of biological processes mainly at the level of translation. This study investigated the possible involvement of microRNAs in gene regulation relevant to neuropathic pain. The analyses focused on a sensory organ-specific cluster of microRNAs that includes miR-96, -182, and -183. RT-PCR analyses confirmed that these microRNAs were highly enriched in the dorsal root ganglion (DRG) of adult rats. Using the L5 spinal nerve ligation (SNL) model of chronic neuropathic pain, we observed a significant reduction in expression of these microRNAs in injured DRG neurons compared to controls. In situ hybridization and immunohistochemical analyses revealed that these microRNAs are expressed in both myelinated (N52 positive) and unmyelinated (IB4 positive) primary afferent neurons. They also revealed that the intracellular distributions of the microRNAs in DRG neurons were dramatically altered in animals with mechanical hypersensitivity. Whereas microRNAs were uniformly distributed within the DRG soma of non-allodynic animals, they were preferentially localized to the periphery of neurons in allodynic animals. The redistribution of microRNAs was associated with changes in the distribution of the stress granule protein TIA-1. These data demonstrate that SNL induces changes in expression levels and patterns of miR-96, -182, and -183, implying their possible contribution to chronic neuropathic pain through translational regulation of pain-relevant genes. Moreover, stress granules were suggested to be assembled and associated with microRNAs after SNL, which may play a role in modification of microRNA-mediated gene regulation in DRG neurons. PMID:19699278
Raman microspectroscopy for visualization of peripheral nerves
NASA Astrophysics Data System (ADS)
Minamikawa, Takeo; Harada, Yoshinori; Koizumi, Noriaki; Takamatsu, Tetsuro
The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery is essential for improving quality of life of patients. To preserve peripheral nerves, detection of ne peripheral nerves that cannot be identi ed by human eye or under white light imaging is necessary. In this study, we sought to provide a proof-of-principle demonstration of a label-free detection technique of peripheral nerve tissues against adjacent tissues that employs spontaneous Raman microspectroscopy. A line-illumination confocal Raman microscope was used for the experiment. A laser operating at the wavelength of 532 nm was used as an excitation laser light. We obtained Raman spectra of peripheral nerve, brous connective tissue, skeletal muscle, blood vessel, and adipose tissue of Wistar rats, and extracted speci c spectral features of peripheral nerves and adjacent tissues. By applying multivariate image analysis, peripheral nerves were clearly detected against adjacent tissues without any preprocessing neither xation nor staining. These results suggest the potential of the Raman spectroscopic observation for noninvasive and label-free nerve detection, and we expect this method could be a key technique for nerve-sparing surgery.
Effects of safranal, a constituent of saffron, and vitamin E on nerve functions and histopathology following crush injury of sciatic nerve in rats.
Tamaddonfard, Esmaeal; Farshid, Amir Abbas; Maroufi, Shirin; Kazemi-Shojaei, Sharare; Erfanparast, Amir; Asri-Rezaei, Siamak; Taati, Mina; Dabbaghi, Milad; Escort, Mona
Safranal is one of the major components of saffron and has many biological effects such as antioxidant property. The present study investigated the effects of safranal on sciatic nerve function after induction of crush injury. We also used of vitamin E as a reference potent antioxidant agent. In anesthetized rats, right sciatic nerve was crushed using a small haemostatic forceps. Functional recovery was assessed using sciatic functional index (SFI). Acetone spray and von Frey filament tests were used for neuropathic pain assay. Histopathological changes including severities of Wallerian degeneration of sciatic nerve and gastrocnemius muscle atrophy were investigated by light microscopy. Blood levels of malodialdehyde (MDA) were also measured. The SFI values were accelerated, cold and mechanical allodynia were suppressed, the severities of Wallerian degeneration and muscular atrophy were improved, and the increased MDA level was reversed with 10 consecutive days intraperitoneal injections of 0.2 and 0.8 mg/kg of safranal and 100 mg/kg of vitamin E. It is concluded that safranal and vitamin E produced same improving effects on crushed-injured sciatic nerve functions. Inhibition of oxidative stress pathway may be involved in improving effects of safranal and vitamin E on functions and histopathology of an injured peripheral nerve. PMID:24315349
Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury.
Hoeber, Jan; Trolle, Carl; Konig, Niclas; Du, Zhongwei; Gallo, Alessandro; Hermans, Emmanuel; Aldskogius, Hakan; Shortland, Peter; Zhang, Su-Chun; Deumens, Ronald; Kozlova, Elena N
Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system. PMID:26053681
Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury
Hoeber, Jan; Trolle, Carl; Konig, Niclas; Du, Zhongwei; Gallo, Alessandro; Hermans, Emmanuel; Aldskogius, Hakan; Shortland, Peter; Zhang, Su-Chun; Deumens, Ronald; Kozlova, Elena N.
Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system. PMID:26053681
Different effects of intracranial and intraorbital section of the optic nerve on the functional responses of rat retinal ganglion cells
L. Domenici; A. Gravina; N. Berardi; L. Maffei
A lesion to the optic nerve of adult mammals leads to the retrograde degeneration and finally to the death of injured retinal ganglion cells. In this study, we have evaluated the effects induced by different sites of axotomy on the functional changes occurring in the retinal ganglion cells after optic nerve section. We have investigated the functional properties of retinal
IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses
Ray, Arundhati; Treloar, Helen B.
Here, we investigated an Immunoglobulin (Ig) superfamily protein IgSF8 which is abundantly expressed in olfactory sensory neuron (OSN) axons and their developing synapses. We demonstrate that expression of IgSF8 within synaptic neuropil is transitory, limited to the period of glomerular formation. Glomerular expression decreases after synaptic maturation and compartmental glomerular organization is achieved, although expression is maintained at high levels within the olfactory nerve layer (ONL). Immunoprecipitations indicate that IgSF8 interacts with tetraspanin CD9 in the olfactory bulb (OB). CD9 is a component of tetraspanin-enriched microdomains (TEMs), specialized microdomains of the plasma membrane known to regulate cell morphology, motility, invasion, fusion and signaling, in both the nervous and immune systems, as well as in tumors. In vitro, both IgSF8 and CD9 localize to puncta within axons and growth cones of OSNs, consistent with TEM localization. When the olfactory epithelium (OE) was lesioned, forcing OSN regeneration en masse, IgSF8 was once again able to be detected in OSN axons terminals as synapses were reestablished. Finally, we halted synaptic maturation within glomeruli by unilaterally blocking functional activity and found that IgSF8 did not undergo exclusion from this subcellular compartment and instead continued to be detected in adult glomeruli. These data support the hypothesis that IgSF8 facilitates OSN synapse formation. PMID:22687584
Sensory Aid Use and the Development of Communicative Function.
ERIC Educational Resources Information Center
Nicholas, Johanna Grant
Natural language conversational samples were collected from hearing-impaired preschoolers who were either using cochlear implants, tactile aids, or hearing aids over a 33-month period. Children using cochlear implants increased their overall communicativeness, their breadth of functions, and their use of intelligible speech faster than other…
Purpose:Laparoscopic varicocelectomy is a minimally invasive option for varicoceles in children. Occasional reports of nerve injury after inguinal laparoscopic procedures have been published. There is anatomical variation in the sensory innervation of the anterior thigh and variable branching patterns of the nerves involved. We report a retrospective analysis of our patients, focusing on the incidence of sensory changes on the
Serial Vagus Nerve Stimulation Functional MRI in Treatment-Resistant Depression
Ziad Nahas; Charlotte Teneback; Jeong-Ho Chae; Qiwen Mu; Chris Molnar; Frank A Kozel; John Walker; Berry Anderson; Jejo Koola; Samet Kose; Mikhail Lomarev; Daryl E Bohning; Mark S George
Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic
Identification of Nerves in Ultrasound Scans Using a Modified Mumford-Shah Functional
Damelin, Steven
in medical imaging is ultrasound, since it does not use ionizing radiation which imposes potential hazardsIdentification of Nerves in Ultrasound Scans Using a Modified Mumford-Shah Functional and Prior Information Jung-Ha An, Paul Bigeleisen, and Steven Damelin Abstract--Ultrasound scans have many important
Functional laser Doppler flowmetry of the optic nerve: physiological aspects and clinical applications
Charles E. Riva; Benedetto Falsini
The present paper reviews the methodology and clinical results of recording, by laser Doppler flowmetry, the hemodynamic response of the optic nerve head elicited by visual stimulation. The basic mechanism underlying this novel technique (which is called here functional laser Doppler flowmetry (FLDF)) is the coupling between visually evoked neural activity and vascular activity within the neural tissue of the
Structure/Function assessment of synapses at motor nerve terminals
Johnstone, A. F. M.; Viele, K.; Cooper, R. L.
The release of transmitter at neuromuscular junctions (NMJ) of the opener muscle in crayfish is quantal in nature. This NMJ offers the advantage of being able to record quantal events at specific visually identified release sites, thus allowing measurement of the physiological parameters of vesicle release and its response to be directly correlated with synaptic structure. These experiments take advantage of areas between the varicosities on the nerve terminal that we define as "stems". Stems were chosen as the region to study because of their low synaptic output due to fewer synaptic sites. Through 3-D reconstruction from hundreds of serial sections, obtained by transmission electron microscopy (TEM), at a site in which focal macropatch recordings were obtained, the number of synapses and AZs are revealed. Thus, physiological profiles with various stimulation conditions can be assessed in regards to direct synaptic structure. Here we used the properties of the quantal shape to determine if distinct subsets of quantal signatures existed and if differences in the distributions are present depending on the frequency of stimulation. Such a quantal signature could come about by parameters of area, rise time, peak amplitude, latency and tau decay. In this study, it is shown that even at defined sites on the stem, with few active zones, synaptic transmission is still complex and the quantal responses appear to be variable even for a given synapse over time. In this study we could not identify a quantal signature for the conditions utilized. PMID:20730805
A Pilot Study Examining Activity Participation, Sensory Responsiveness, and Competence in Children with High Functioning Autism Spectrum Disorder
ERIC Educational Resources Information Center
Reynolds, Stacey; Bendixen, Roxanna M.; Lawrence, Tami; Lane, Shelly J.
This pilot study explored activity patterns in children with and without ASD and examined the role of sensory responsiveness in determining children's level of competence in activity performance. Twenty-six children with high functioning ASD and twenty-six typically-developing children 6-12 years old were assessed using the Sensory Profile and the…
Immunohistochemical analysis of the adhesive papillae of Botrylloides leachi (Chordata, Tunicata, Ascidiacea): Implications for their sensory function
R. Pennati; G. Zega; S. Groppelli; F. De Bernardi
Most ascidian larvae settle and begin adhesion by means of three mucus secreting and sensory organs, the adhesive papillae or palps. However, the adhesive papillae of Botrylloides genus larvae, despite their name, have only a sensory function. By immunohistochemical localization of serotonin and ??tubulin, we demonstrated that the adhesive papillae of Botrylloides leachi contain two distinct types of neurons with
Redox and Nitric Oxide-Mediated Regulation of Sensory Neuron Ion Channel Function
Abstract Significance: Reactive oxygen and nitrogen species (ROS and RNS, respectively) can intimately control neuronal excitability and synaptic strength by regulating the function of many ion channels. In peripheral sensory neurons, such regulation contributes towards the control of somatosensory processing; therefore, understanding the mechanisms of such regulation is necessary for the development of new therapeutic strategies and for the treatment of sensory dysfunctions, such as chronic pain. Recent Advances: Tremendous progress in deciphering nitric oxide (NO) and ROS signaling in the nervous system has been made in recent decades. This includes the recognition of these molecules as important second messengers and the elucidation of their metabolic pathways and cellular targets. Mounting evidence suggests that these targets include many ion channels which can be directly or indirectly modulated by ROS and NO. However, the mechanisms specific to sensory neurons are still poorly understood. This review will therefore summarize recent findings that highlight the complex nature of the signaling pathways involved in redox/NO regulation of sensory neuron ion channels and excitability; references to redox mechanisms described in other neuron types will be made where necessary. Critical Issues: The complexity and interplay within the redox, NO, and other gasotransmitter modulation of protein function are still largely unresolved. Issues of specificity and intracellular localization of these signaling cascades will also be addressed. Future Directions: Since our understanding of ROS and RNS signaling in sensory neurons is limited, there is a multitude of future directions; one of the most important issues for further study is the establishment of the exact roles that these signaling pathways play in pain processing and the translation of this understanding into new therapeutics. Antioxid. Redox Signal. 22, 486–504. PMID:24735331
Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses
Vaughan, Cheryl H.
Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (Tc) and IBAT (TIBAT) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. TIBAT and Tc were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure. PMID:22378771
The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats
Yukari Date; Noboru Murakami; Koji Toshinai; Shigeru Matsukura; Akira Niijima; Hisayuki Matsuo; Kenji Kangawa; Masamitsu Nakazato
Background & Aims: Visceral sensory information is transmitted to the brain through the afferent vagus nerve. Ghrelin, a peptide primarily produced in the stomach, stimulates both feeding and growth hormone (GH) secretion. How stomach-derived ghrelin exerts these central actions is still unknown. Here we determined the role of the gastric afferent vagal nerve in ghrelin's functions. Methods: Food intake and
Assessment of sensory function in neonatal sheep with somatosensory evoked potentials: methodology and normative data
Charles D. Yingling; Claudia Meuli-Simmen; Martin Meuli; Gregory B. Timmel; N. Scott Adzick; Michael Harrison
Fetal sheep are increasingly used as animal models for fetal surgical interventions such as repair of myelomeningocele. Since\\u000a behavioral observations cannot provide objective information about preservation of sensory function, we have developed a technique\\u000a for reliably recording somatosensory evoked potentials in neonatal sheep. We determined anatomic criteria for placement of\\u000a recording electrodes over the somatosensory cortex using external landmarks, and
Sensory biology: it takes Piezo2 to tango.
Vásquez, Valeria; Scherrer, Gregory; Goodman, Miriam B
A trio of papers has resolved an outstanding controversy regarding the function of Merkel cells and their afferent nerve fiber partners. Merkel cells sense mechanical stimuli (through Piezo2), fire action potentials, and are sufficient to activate downstream sensory neurons. PMID:24937283
Loudness function derives from data on electrical discharge rates in auditory nerve fibers
NASA Technical Reports Server (NTRS)
Howes, W. L.
Judgements of the loudness of pure-tone sound stimuli yield a loudness function which relates perceived loudness to stimulus amplitude. A loudness function is derived from physical evidence alone without regard to human judgments. The resultant loudness function is L=K(q-q0), where L is loudness, q is effective sound pressure (specifically q0 at the loudness threshold), and K is generally a weak function of the number of stimulated auditory nerve fibers. The predicted function is in agreement with loudness judgment data reported by Warren, which imply that, in the suprathreshold loudness regime, decreasing the sound-pressure level by 6 db results in halving the loudness.
Functional recovery from sciatic nerve crush lesion in the rat correlates with individual differences in responses to chronic intermittent stress
W. H. Gispen; N. L. U. Meeteren; J. H. Brakkee; P. J. M. Helders; V. M. Wiegant
The aim of the present study was to monitor the influence of chronic stress on functional recovery from a sciatic nerve crush lesion in the rat. Male Wistar rats underwent standard unilateral sciatic nerve crush. Subsequently, chronic stress was induced during the recovery phase using a daily 30 min shock box session where rats received three electric footshocks each session
Targeted delivery of Tet1 peptide functionalized polymersomes to the rat cochlear nerve
Zhang, Ya; Zhang, Weikai; Johnston, Alexander H; Newman, Tracey A; Pyykkö, Ilmari; Zou, Jing
Polymersomes are nanosized vesicles formed from amphiphilic block copolymers, and have been identified as potential drug delivery vehicles to the inner ear. The aim of this study was to provide targeting to specific cells within the inner ear by functionalizing the polymersome surface with Tet1 peptide sequence. Tet1 peptide specifically binds to the trisialoganglioside clostridial toxin receptor on neurons and was expected to target the polymersomes toward the cochlear nerve. The Tet1 functionalized PEG-b-PCL polymersomes were administered using routine drug delivery routes: transtympanic injection and cochleostomy. Delivery via cochleostomy of Tet1 functionalized polymersomes resulted in cochlear nerve targeting; in contrast this was not seen after transtympanic injection. PMID:22403485
Targeted delivery of Tet1 peptide functionalized polymersomes to the rat cochlear nerve.
Zhang, Ya; Zhang, Weikai; Johnston, Alexander H; Newman, Tracey A; Pyykkö, Ilmari; Zou, Jing
Polymersomes are nanosized vesicles formed from amphiphilic block copolymers, and have been identified as potential drug delivery vehicles to the inner ear. The aim of this study was to provide targeting to specific cells within the inner ear by functionalizing the polymersome surface with Tet1 peptide sequence. Tet1 peptide specifically binds to the trisialoganglioside clostridial toxin receptor on neurons and was expected to target the polymersomes toward the cochlear nerve. The Tet1 functionalized PEG-b-PCL polymersomes were administered using routine drug delivery routes: transtympanic injection and cochleostomy. Delivery via cochleostomy of Tet1 functionalized polymersomes resulted in cochlear nerve targeting; in contrast this was not seen after transtympanic injection. PMID:22403485
Chronic inflammatory pure sensory polyradiculoneuropathy: a rare CIDP variant with unusual electrophysiology.
Rajabally, Yusuf A; Wong, Siew L
We describe a patient presenting with progressive upper limb numbness and sensory ataxia of the 4 limbs. Motor nerve conduction studies were completely normal. Sensory electrophysiology showed reduced/absent upper limb sensory action potentials (SAPs). In the lower limbs, SAPs were mostly normal. Sensory conduction velocities were normal. Forearm sensory conduction blocks were present for both median nerves on antidromic testing. The maximal recordable sural SAP was preserved in comparison to maximal recordable radial SAP, consistent with an "abnormal radial normal sural" pattern. Somatosensory evoked potentials were unrecordable for tibial and median nerves. Cerebrospinal fluid protein was raised (0.99 g/L). The patient worsened on oral corticosteroids but subsequently made substantial functional recovery on intravenous immunoglobulins. This case is different to those previously reported of sensory chronic inflammatory demyelinating polyradiculoneuropathy, given its exclusive sensory electrophysiologic presentation, presence of predominant upper limb reduced sensory amplitudes, and detection of sensory conduction blocks. These electrophysiologic features were of paramount importance in establishing diagnosis and effective therapy. PMID:22538310
Processes of excitation in the dendrites and in the soma of single isolated sensory nerve cells of the lobster and crayfish.
The stretch receptor organs of Alexandrowicz in lobster and crayfish possess sensory neurons which have their cell bodies in the periphery. The cell bodies send dendrites into a fine nearby muscle strand and at the opposite pole they give rise to an axon running to the central nervous system. Mechanisms of excitation between dendrites, cell soma, and axon have been studied in completely isolated receptor structures with the cell components under visual observation. Two sensory neuron types were investigated, those which adapt rapidly to stretch, the fast cells, and those which adapt slowly, the slow cells. 1. Potentials recorded from the cell body of the neurons with intracellular leads gave resting potentials of 70 to 80 mv. and action potentials which in fresh preparations exceeded the resting potentials by about 10 to 20 mv. In some experiments chymotrypsin or trypsin was used to make cell impalement easier. They did not appreciably alter resting or action potentials. 2. It has been shown that normally excitation starts in the distal portion of dendrites which are depolarized by stretch deformation. The changed potential within the dendritic terminals can persist for the duration of stretch and is called the generator potential. Secondarily, by electrotonic spread, the generator potential reduces the resting potential of the nearby cell soma. This excitation spread between dendrites and soma is seen best during subthreshold excitation by relatively small stretches of normal cells. It is also seen during the whole range of receptor stretch in neurons in which nerve conduction has been blocked by an anesthetic. The electrotonic changes in the cells are graded, reflecting the magnitude and rate of rise of stretch, and presumably the changing levels of the generator potential. Thus in the present neurons the resting potential and the excitability level of the cell soma can be set and controlled over a wide range by local events within the dendrites. 3. Whenever stretch reduces the resting membrane potential, measured in the relaxed state in the cell body, by 8 to 12 mv. in slow cells and by 17 to 22 mv. in fast cells, conducted impulses are initiated. It is thought that in slow cells conducted impulses are initiated in the dendrites while in fast cells they arise in the cell body or near to it. In fresh preparations the speed of stretch does not appreciably influence the membrane threshold for discharges, while during developing fatigue the firing level is higher when extension is gradual. 4. Some of the specific neuron characteristics are: Fast receptor cells have a relatively high threshold to stretch. During prolonged stretch the depolarization of the cell soma is not well maintained, presumably due to a decline in the generator potential, resulting in cessation of discharges in less than a minute. This appears to be the basis of the relatively rapid adaptation. A residual subthreshold depolarization can persist for many minutes of stretch. Slow cells which resemble the sensory fibers of vertebrate spindles are excited by weak stretch. Their discharge rate remains remarkably constant for long periods. It is concluded that, once threshold excitation is reached, the generator potential within slow cell dendrites is well maintained for the duration of stretch. Possible reasons for differences in discharge properties between fast and slow cells are discussed. 5. If stretch of receptor cells is gradually continued above threshold, the discharge frequency first increases over a considerable range without an appreciable change in the firing level for discharges. Beyond that range the membrane threshold for conducted responses of the cell soma rises, the impulses become smaller, and partial conduction in the soma-axon boundary region occurs. At a critical depolarization level which may be maintained for many minutes, all conduction ceases. These overstretch phenomena are reversible and resemble cathodal block. 6. The following general scheme of excitation is proposed: stretch deformation of dendritic terminals --> generator
Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves
NASA Astrophysics Data System (ADS)
Xiaoyan, Shen; Zhigong, Wang; Xiaoying, Lü; Shushan, Xie; Zonghao, Huang
According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-?m CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.
Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons.
Roberson, David P; Gudes, Sagi; Sprague, Jared M; Patoski, Haley A W; Robson, Victoria K; Blasl, Felix; Duan, Bo; Oh, Seog Bae; Bean, Bruce P; Ma, Qiufu; Binshtok, Alexander M; Woolf, Clifford J
The peripheral terminals of primary sensory neurons detect histamine and non-histamine itch-provoking ligands through molecularly distinct transduction mechanisms. It remains unclear, however, whether these distinct pruritogens activate the same or different afferent fibers. Using a strategy of reversibly silencing specific subsets of murine pruritogen-sensitive sensory axons by targeted delivery of a charged sodium-channel blocker, we found that functional blockade of histamine itch did not affect the itch evoked by chloroquine or SLIGRL-NH2, and vice versa. Notably, blocking itch-generating fibers did not reduce pain-associated behavior. However, silencing TRPV1(+) or TRPA1(+) neurons allowed allyl isothiocyanate or capsaicin, respectively, to evoke itch, implying that certain peripheral afferents may normally indirectly inhibit algogens from eliciting itch. These findings support the presence of functionally distinct sets of itch-generating neurons and suggest that targeted silencing of activated sensory fibers may represent a clinically useful anti-pruritic therapeutic approach for histaminergic and non-histaminergic pruritus. PMID:23685721
Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons
Roberson, David P.; Gudes, Sagi; Sprague, Jared M.; Patoski, Haley A. W.; Robson, Victoria K.; Blasl, Felix; Duan, Bo; Oh, Seog Bae; Bean, Bruce P.; Ma, Qiufu
The peripheral terminals of primary sensory neurons detect histamine and non-histamine itch-provoking ligands through molecularly distinct transduction mechanisms. It remains unclear, however, whether these distinct pruritogens activate the same or different afferent fibers. We utilized a strategy of reversibly silencing specific subsets of murine pruritogen-sensitive sensory axons by targeted delivery of a charged sodium-channel blocker and found that functional blockade of histamine itch did not affect the itch evoked by chloroquine or SLIGRL-NH2, and vice versa. Notably, blocking itch-generating fibers did not reduce pain-associated behavior. However, silencing TRPV1+ or TRPA1+ neurons allowed AITC or capsaicin respectively to evoke itch, implying that certain peripheral afferents may normally indirectly inhibit algogens from eliciting itch. These findings support the presence of functionally distinct sets of itch-generating neurons and suggest that targeted silencing of activated sensory fibers may represent a clinically useful anti-pruritic therapeutic approach for histaminergic and non-histaminergic pruritus. PMID:23685721
Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence for the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines.
Pawlik, M W; Kwiecien, S; Pajdo, R; Ptak-Belowska, A; Brzozowski, B; Krzysiek-Maczka, G; Strzalka, M; Konturek, S J; Brzozowski, T
Gastroesophageal reflux disease (GERD) is a global disease rapidly increasing among world population. The pathogenesis of reflux esophagitis which is considered as the early stage of GERD is complex, resulting from an imbalance between aggressive factors damaging the esophagus and a number of the natural defense mechanisms. The esophageal mucosa is in a state of continuous exposure to potentially damaging endogenous and exogenous factors. Important aggressive components of gastric refluxate include acid and pepsin and also pancreatic enzymes and bile. Among aggressive factors of exogenous origin, cigarette smoking, non-steroidal anti-inflammatory drugs (NSAID), and steroids are of the utmost importance. The basic level of esophageal defense against acid-pepsin damage consists of the anti-reflux mechanisms such as the luminal acid clearance and removal of the esophageal contents and neutralization of luminal acidity. In addition the esophageal mucosal protection includes the presence of pre-epithelial, epithelial and post-epithelial cellular and functional components. Recently, the progress have been made in the understanding of role of the heptapeptide member of the renin-angiotensin system (RAS), angiotensin-(1-7) (Ang-(1-7)) in the control of gastrointestinal functions. It has been shown that all components of local RAS including Ang-(1-7) are detectable in the gastrointestinal wall including not only the stomach but also the esophagus. Previous studies revealed that Ang-(1-7), which is an important component of the RAS, exerts vasodilatory, anti-inflammatory and antioxidant activities in the stomach. Ang-(1-7) was recently implicated in gastroprotection, but its effects on esophageal mucosa in a rodent model of reflux esophagitis and in human subjects presenting GERD symptoms have not been explored. The present study was aimed to evaluate the possible protective effects of Ang-(1-7) and Mas-receptors upon esophageal mucosal damage in acute reflux esophagitis (RE) induced in anesthetized rats by ligating the pylorus and the limiting ridge (a transitional region between the forestomach and the corpus of stomach). Consequently, the total gastric reservoir to store gastric juice was greatly diminished, resulting in the reflux of this juice into the esophagus. Because Mas receptors are functionally linked to nitric oxide (NO) formation, we also studied involvement of endogenous NO in the mediation of protective and circulatory effects of exogenous Ang-(1-7). Moreover, an attempt was made to assess the possible role of sensory neurons in the modulation of the protective effects exerted by Ang-(1-7)/Mas receptor system. Six series of rats were pretreated 30 min before induction of RE with 1) vehicle (saline), 2) Ang-(1-7) (5-50 ?g/kg i.p.), 3) A779 (50 ?g/kg i.p.), the selective Mas receptor antagonist applied alone, 4) Ang-(1-7) (50 ?g/kg i.p.) combined with A779, 5) L-NNA (20 mg/kg i.p.) administered alone, and 6) Ang-(1-7) (50 ?g/kg i.p.) combined with L-NNA. In separate group of rats, capsaicin (total dosage of 125 mg/kg within three days) was administered s.c. 2 weeks before the induction of RE to induce functional ablation of sensory nerves. Rats with intact sensory nerves and those with capsaicin-induced sensory denervation received vehicle (saline) or Ang-(1-7) (50 ?g/kg i.p.) to determine whether this vasoactive metabolite of angiotensin I could be also effective in rats with capsaicin-induced impairment of the synthesis and release of sensory neuropeptides such as CGRP. Four hours after induction of RE, the mucosal damage was graded with mucosal lesion index (LI) from 0 to 6, the esophageal microcirculatory blood flow (EBF) was determined by H2-gas clearance technique and plasma level of pro-inflammatory cytokines interleukin-1b (IL-1?), and tumor necrosis factor-? (TNF-?) was determined by ELISA. The expression of proinflammatory factors including COX-2, cytokine IL-1? and hypoxia inducible factor 1alpha (Hif1?) was analyzed in the esophageal mucosal biopsies. In rats with RE, the esophageal LI was signi
Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?
Radtke, Christine; Kocsis, Jeffery D.
Successful nerve regeneration after nerve trauma is not only important for the restoration of motor and sensory functions, but also to reduce the potential for abnormal sensory impulse generation that can occur following neuroma formation. Satisfying functional results after severe lesions are difficult to achieve and the development of interventional methods to achieve optimal functional recovery after peripheral nerve injury is of increasing clinical interest. Olfactory ensheathing cells (OECs) have been used to improve axonal regeneration and functional outcome in a number of studies in spinal cord injury models. The rationale is that the OECs may provide trophic support and a permissive environment for axonal regeneration. The experimental transplantation of OECs to support and enhance peripheral nerve regeneration is much more limited. This chapter reviews studies using OECs as an experimental cell therapy to improve peripheral nerve regeneration. PMID:23202929
Corneal confocal microscopy reveals trigeminal small sensory fiber neuropathy in amyotrophic lateral sclerosis
Ferrari, Giulio; Grisan, Enrico; Scarpa, Fabio; Fazio, Raffaella; Comola, Mauro; Quattrini, Angelo; Comi, Giancarlo; Rama, Paolo; Riva, Nilo
Although subclinical involvement of sensory neurons in amyotrophic lateral sclerosis (ALS) has been previously demonstrated, corneal small fiber sensory neuropathy has not been reported to-date. We examined a group of sporadic ALS patients with corneal confocal microscopy, a recently developed imaging technique allowing in vivo observation of corneal small sensory fibers. Corneal confocal microscopy (CCM) examination revealed a reduction of corneal small fiber sensory nerve number and branching in ALS patients. Quantitative analysis demonstrated an increase in tortuosity and reduction in length and fractal dimension of ALS patients' corneal nerve fibers compared to age-matched controls. Moreover, bulbar function disability scores were significantly related to measures of corneal nerve fibers anatomical damage. Our study demonstrates for the first time a corneal small fiber sensory neuropathy in ALS patients. This finding further suggests a link between sporadic ALS and facial-onset sensory and motor neuronopathy (FOSMN) syndrome, a rare condition characterized by early sensory symptoms (with trigeminal nerve distribution), followed by wasting and weakness of bulbar and upper limb muscles. In addition, the finding supports a model of neurodegeneration in ALS as a focally advancing process. PMID:25360111
Specialized Nerve Tests: EMG, NCV and SSEP
... spinal cord are able to send and receive sensory information like pain, temperature and touch. When ordering ... SSEP is used to double check whether the sensory part of the nerve is working correctly. What ...
Multiple functions of the paranodal junction of myelinated nerve fibers.
Rosenbluth, Jack
Myelin sheaths include an extraordinary structure, the "paranodal axoglial junction" (PNJ), which attaches the sheath to the axon at each end of each myelin segment. Its size is enormous and its structure unique. Here we review past and current studies showing that this junction can serve multiple functions in maintaining reliable saltatory conduction. The present evidence points to three functions in particular. 1) It seals the myelin sheath to the axon to prevent major shunting of nodal action currents beneath the myelin sheath while still leaving a narrow channel interconnecting the internodal periaxonal space with the perinodal space. This pathway represents a potential route through which juxtaparanodal and internodal channels can influence nodal activity and through which nutrients, such as glucose, and other metabolites can diffuse to and from the internodal periaxonal space. 2) It serves as a mechanism for maintaining discrete, differentiated axolemmal domains at and around the node of Ranvier by acting as a barrier to the lateral movement of ion channel complexes within the axolemma, thus concentrating voltage-gated sodium channels at the node and segregating fast voltage-gated potassium channels to the juxtaparanode under the myelin sheath. 3) It attaches the myelin sheath to the axon on either side of the node and can thus maintain nodal dimensions in the face of mechanical stresses associated with stretch or other local factors that might cause disjunction. It is therefore the likely means for maintaining constancy of nodal surface area and electrical parameters essential for consistency in conduction. PMID:19224642
Functional assessment of sensory functions after photothrombotic stroke in the barrel field of mice.
Liguz-Lecznar, Monika; Zakrzewska, Renata; Daniszewska, Katarzyna; Kossut, Malgorzata
Motor, sensory and cognitive deficits are common impairments observed in human stroke as well as in animal stroke models. Using a battery of behavioural tests we assessed sensorimotor deficits after photothrombotic stroke localized within or beyond cortical representation of mouse sensory vibrissae. We found restricted, modality specific behavioural consequences in the acute post-stroke period. Among incorporated tests, adhesive removal test, novelty exploration test and sensory labyrinth task were sensitive to the somatosensory cortical deficits. Injured animals explored new objects significantly longer, they also needed distinctly more time to contact and to remove the adhesive tape placed on whiskers contralateral to the infarct. Moreover, we observed that after stroke animals were unable to solve the sensory labyrinth depending only upon tactile sensation from whiskers with injured cortical representation. Spontaneous recovery could be observed within the first post-stroke week for adhesive tape removal and within 14 days for labyrinth performance. However, for the novel object exploration we did not observed the recovery for the period of 18 days after stroke. Moreover, new object exploration test performance differed between the somatosensory and visual cortical impairments. We suggest that those three tests might be valuable in assessing the usefulness of therapies designed to support brain repair after experimental stroke. PMID:24388975
Dual simulated childbirth injuries result in slowed recovery of pudendal nerve and urethral function
Jiang, Hai-Hong; Pan, Hui Q; Gustilo-Ashby, A. Marcus; Gill, Bradley; Glaab, Jonathan; Zaszczurynski, Paul; Damaser, Margot
Aims Pelvic floor muscle trauma and pudendal nerve injury have been implicated in stress urinary incontinence (SUI) development after childbirth. In this study, we investigated how combinations of these injuries affect recovery. Methods Sixty-seven female Sprague-Dawley rats underwent vaginal distension (VD), pudendal nerve crush (PNC), PNC and VD (PNC+VD), pudendal nerve transection (PNT), or served as unmanipulated controls. Four days, 3 weeks, or 6 weeks after injury, we simultaneously recorded pudendal nerve motor branch potentials (PNMBP), external urethral sphincter electromyography (EUS EMG), and transurethral bladder pressure under urethane anesthesia. The presence of a guarding reflex (increased frequency & amplitude of PNMBP or EUS EMG activity) during leak point pressure (LPP) testing was determined. Results Controls consistently demonstrated a guarding reflex. Four days after VD, EUS EMG activity was eliminated, but PNMBP activity reflected the guarding reflex; EUS EMG activity recovered after 3 weeks. Four days after PNC, both EUS EMG and PNMBP activity were eliminated, but demonstrated significant recovery at 3 weeks. Four days after PNC+VD both EUS EMG and nerve activity were eliminated, and little recovery was observed after 3 weeks with significant recovery of the guarding reflex 6 weeks after injury. Little recovery was observed at all time points after PNT. LPP results mirrored the reduction in EUS EMG activity. Conclusion Functional recovery occurs more slowly after PNC+VD than after either PNC or VD alone. Future work will be aimed at testing methods to facilitate neuroregeneration and recovery after this clinically relevant dual injury. PMID:18973146
An Analysis of Hamster Afferent Taste Nerve Response Functions
Frank, Marion
Sensitivities to moderately intense stimuli representing four taste qualities to man were determined for 79 hamster chorda tympani fibers. Some fibers were very sensitive to sucrose, sodium chloride, or hydrochloric acid, but none were very sensitive to quinine. These sensitivities were not randomly distributed among fibers: the sucrose sensitivity was separated from and negatively correlated with the other sensitivities which were associated and positively correlated with each other. Moreover, there were a limited number of sensitivity patterns: (a) fibers responding best to sucrose responded second-best to salt, less to acid, not to quinine; (b) fibers responding best to salt either responded second-best to sucrose and not to acid or quinine; or second-best to acid, less to quinine, and not to sucrose; and (c) fibers responding best to acid responded second-best to salt, more to quinine, and less to sucrose than other fibers. Therefore, if four stimuli of different taste qualities are ordered from acceptable to unacceptable, neural response functions of most hamster chorda tympani taste fibers peak at one point. Sensitivities to nine other moderately intense stimuli which vary in quality to man were also determined for 46–49 of the fibers. Sensitivities to sweet stimuli were always associated with each other and separated from sensitivities to nonsweet stimuli. Sensitivities to nonsweet stimuli were all associated with each other; however, the strongest correlations were between sensitivities to stimuli of like quality, e.g., the three acids or the two sodium salts. PMID:4705639
Burn-Induced Organ Dysfunction: Vagus Nerve Stimulation Improves Cardiac Function
Niederbichler, Andreas D.; Papst, Stephan; Claassen, Leif; Jokuszies, Andreas; Ipaktchi, Kyros; Reimers, Kerstin; Hirsch, Tobias; Steinstraesser, Lars; Kraft, Theresia; Vogt, Peter M.
Introduction: Many studies have demonstrated the existence of an anti-inflammatory, parasympathetic pathway, termed as the inflammatory reflex. Burn-induced heart failure has been investigated in many previous studies. Proinflammatory cytokines, such as TNF-?, IL-1?, and IL-6, have been shown to play a key pathogenetic role and vagus nerve stimulation attenuates proinflammatory cytokine production. This study was designed to evaluate postburn alterations of cardiac functional parameters after vagal electrostimulation. Material and Methods: A 30% total body surface area standardized, full-thickness rat burn model was used. Electric stimulation of the vagus nerve was performed. The following functional cardiac parameters were measured by ventricular microcatheterization: Maximal and minimal left ventricular pressure, mean left ventricular pressure, end-diastolic pressure (EDP), positive and negative pressure rise and fall (±dP/dt), cardiac contractility index, and assessment of the heart rate. Results: Vagus nerve stimulation improved maximal and minimal left ventricular pressure values compared with burn-only animals. End-diastolic pressure was elevated significantly in stimulated animals; however, EDP values were comparable with those in sham-injured animals. Analyzing positive and negative pressure development, ±dP/dt was restored to levels measured in sham-injured animals but not to control animal levels. No variations in heart rate were found. Conclusion: We as well as others have shown that inflammation after burn injury is a key pathogenetic element, and this study provides new evidence that cardiac function is also improved by vagus nerve stimulation. These results lead us to consider novel therapeutic options for the treatment of postburn cardiac dysfunction. PMID:20596235
Reconstruction of upper-extremity peripheral-nerve injuries with ePTFE conduits.
Stanec, S; Stanec, Z
This reported investigation was designed to determine the role of a new synthetic conduit-expanded polytetrafluoroethylene (ePTFE) tube--in clinical repair of median and ulnar nerves in the upper extremities. The main goals of this study were: to determine the effectiveness of the ePTFE conduit in clinical nerve reconstruction; to evaluate the potential of this technique in reconstruction of various nerve gaps (1.5 to 6 cm); and to analyze the results of repair with the ePTFE tube regarding different mechanisms of injury. Forty-three patients were evaluated. They had upper-extremity peripheral-nerve injuries (21 injuries to the median nerve, and 22 ulnar nerve injuries) located at the various levels of the upper extremities. All surgical procedures described in the study were secondary reconstructions, and the average delay from injury to repair was 4.2 months. With regard to the nerve-gap lengths, patients were categorized in two groups. Group 1 (gaps from 1.5 to 4 cm) included 28 patients (17 median nerve injuries and 11 ulnar nerve injuries), and Group 2 (gaps from 4.1 to 6 cm) comprised 15 patients (4 median nerve injuries and 11 ulnar nerve injuries). Results showed that 78.6 percent of patients from Group 1 demonstrated functional motor and sensory recovery, while reconstruction of only 13.3 percent of peripheral nerves from Group 2 resulted in useful reinnervation. According to published results, ePTFE conduit is a reliable and successful surgical procedure for nerve repair in reconstruction of nerve gaps up to 4 cm between the ends of median and ulnar nerves in various levels of the upper extremity. Because of its properties, ePTFE conduit has the advantages of promoting better nerve regeneration, compared to other synthetic tubes, especially in reconstruction of proximal nerve injuries, larger nerve gaps, and in cases with unfavorable mechanisms of nerve injury. PMID:9618088
The anatomy and fine structure of the echidna Tachyglossus aculeatus snout with respect to its different trigeminal sensory receptors including the electroreceptors
K. H. Andres; A. Iggo; U. Proske
The gross anatomy and nerve supply of the bill of echidna (Tachyglossus aculeatus) is described in relation to its function as an outstanding sensory organ. The sensory innervation of the skin of the echidna snout was investigated by means of frontal serial sections, after decalcification of the specimens. A comprehensive light and electron microscopic description of the location and fine
The RhoGEF Trio Functions in Sculpting Class Specific Dendrite Morphogenesis in Drosophila Sensory Neurons
Iyer, Srividya Chandramouli; Wang, Dennis; Iyer, Eswar Prasad R.; Trunnell, Sarah A.; Meduri, Ramakrishna; Shinwari, Riaz; Sulkowski, Mikolaj J.; Cox, Daniel N.
Background As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures. Methodology/Principal Findings Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis. Conclusions/Significance Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation. PMID:22442703
Successful tactile based visual sensory substitution use functions independently of visual pathway integrity
Lee, Vincent K.; Nau, Amy C.; Laymon, Charles; Chan, Kevin C.; Rosario, Bedda L.; Fisher, Chris
Purpose: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort). Methods: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). Results: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p ? 0.025) in the bilateral optic radiations and some visual association connections between all three groups. No relationship was found between FA and functional performance with the BrainPort. Discussion: All subjects showed performance improvements using the BrainPort irrespective of nature and duration of blindness. Definite brain areas with significant microstructural integrity changes exist among PB, AB, and NC, and these variations are most pronounced in the visual pathways. However, the use of sensory substitution devices is feasible irrespective of microstructural integrity of the primary visual pathways between the eye and the brain. Therefore, tongue based devices devices may be usable for a broad array of non-sighted patients. PMID:24860473
[Axon-reflex based nerve fiber function assessment in the detection of autonomic neuropathy].
Siepmann, T; Illigens, B M-W; Reichmann, H; Ziemssen, T
Axon-reflex-based tests of peripheral small nerve fiber function including techniques to quantify vasomotor and sudomotor responses following acetylcholine iontophoresis are used in the assessment of autonomic neuropathy. However, the established axon-reflex-based techniques, laser Doppler flowmetry (LDF) to assess vasomotor function and quantitative sudomotor axon-reflex test (QSART) to measure sudomotor function, are limited by technically demanding settings as well as interindividual variability and are therefore restricted to specialized clinical centers. New axon-reflex tests are characterized by quantification of axon responses with both temporal and spatial resolution and include "laser Doppler imaging (LDI) axon-reflex flare area test" to assess vasomotor function, the quantitative direct and indirect test of sudomotor function (QDIRT) to quantify sudomotor function, as well as the quantitative pilomotor axon-reflex test (QPART), a technique to measure pilomotor nerve fiber function using adrenergic cutaneous stimulation through phenylephrine iontophoresis. The effectiveness of new axon-reflex tests in the assessment of neuropathy is currently being investigated in clinical studies. PMID:25047406
Functional and anatomical characteristics of the nerve-brown adipose interaction in the rat
NASA Technical Reports Server (NTRS)
Flaim, K. E.; Horowitz, J. M.; Horwitz, B. A.
Experiments were conducted on 12 male rats to study the coupling of signals from the sympathetic nervous system to the brown adipose tissue. Analysis of electron photomicrographs revealed considerable morphological heterogeneity among the nerves entering and leaving the interscapular fat pad. In response to electrical simulation of the nerves, the temperature of the brown fat increased following a rapid but transient temperature drop. Such changes were observed only on the ipsilateral side, indicating that the innervation to the interscapular brown fat of the rat is functionally bilateral rather than diffuse. The finding that brown fat is capable of responding in a graded fashion correlates well with observations suggesting that clusters of brown adipocytes may be electrically coupled.
Nerve Regeneration Restores Supraspinal Control of Bladder Function after Complete Spinal Cord Injury
Lin, Ching-Yi; Jiang, Hai-Hong; DePaul, Marc; Lin, Vernon W.
A life-threatening disability after complete spinal cord injury is urinary dysfunction, which is attributable to lack of regeneration of supraspinal pathways that control the bladder. Although numerous strategies have been proposed that can promote the regrowth of severed axons in the adult CNS, at present, the approaches by which this can be accomplished after complete cord transection are quite limited. In the present study, we modified a classic peripheral nerve grafting technique with the use of chondroitinase to facilitate the regeneration of axons across and beyond an extensive thoracic spinal cord transection lesion in adult rats. The novel combination treatment allows for remarkably lengthy regeneration of certain subtypes of brainstem and propriospinal axons across the injury site and is followed by markedly improved urinary function. Our studies provide evidence that an enhanced nerve grafting strategy represents a potential regenerative treatment after severe spinal cord injury. PMID:23804083
Intramuscular nerve distribution in bladder and the relationship between intramuscular ganglia and bladder function in man and dog
Zhao, Zeju; Xu, Qian; Lu, Li; Luo, Xu; Fu, Xiaoyun
In clinical, the relationship between bladder intramuscular nerve and function is also elusive. This study aims to compare the bladder intramuscular nerve distribution and its characteristics and significance in human and dog. Eleven dogs' bladders were stained by Sihler's and HE techniques. Fifteen human bladders were adopted by Sihler's staining, using 10% formaldehyde to fix 12 weeks, 7 by HE dyeing fixes 24 hours. Results indicated that man's bladder was triangularpyramid-shaped. While dog's bladder was spherical-shaped and its muscle fibers arrange were irregularly shaped. Longitudinal muscle of the outer layer is fleshy, the terminal is at the bladder neck without exception, and vesical trigone has relatively obvious three layers of structure. After dyeing dog's bladder was transparent jelly, the nerve was purple color, enter bladder at the ureter-bladder junction with different forms. Man's bladder nerves, no ganglion, were more trivial than that of dogs, and with smaller branches, the large nerve ganglion. The links with the nerve fibers and forms the network on the dog's bladder wall, and the nerve fibers crosses comparatively little on both the left and right sides in the midline. The right nerve branch gains advantage on the man's bladder wall, the situations is opposite on the dog's. In conclusion, bladder nerves which scatter to the bladder wall have branches to lower ureter at the ureter-bladder junction, the structure and distribution of intramuscular nerves are different, the existence of intramuscular ganglia is relating to the bladder function both in man and dog. PMID:25664008
Deletion of Nrf2 impairs functional recovery, reduces clearance of myelin debris and decreases axonal remyelination after peripheral nerve injury
Zhang, Linxia; Johnson, Delinda; Johnson, Jeffrey A.
Oxidative stress is generated in several peripheral nerve injury models. In response to oxidative stress, the transcription factor Nrf2 is activated to induce expression of antioxidant responsive element (ARE) genes. The role of Nrf2 in peripheral nerve injury has not been studied to date. In this study, we used a sciatic nerve crush model to examine how deletion of Nrf2 affects peripheral nerve degeneration and regeneration. Our study demonstrated that functional recovery in the Nrf2-/- mice were impaired compared to the wild type mice after sciatic nerve crush. Larger myelin debris were present in the distal nerve stump of the Nrf2-/- mice than in the wild type mice. The presence of larger myelin debris in the Nrf2-/- mice coincides with less macrophages accumulation in the distal nerve stump. Less accumulation of macrophages may have contributed to slower clearance of myelin and thus resulted in the presence of larger myelin debris. Meanwhile, axonal regeneration is comparatively lower in the Nrf2-/- mice than in the wild type mice. Even after 3 months post the injury, more thinly myelinated axon fibers were present in the Nrf2-/- mice than in the wild type mice. Taken collectively, these data support the concept of therapeutic intervention with Nrf2 activators following nerve injury. PMID:23328769
A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ.
Abdelilah-Seyfried, S; Chan, Y M; Zeng, C; Justice, N J; Younger-Shepherd, S; Sharp, L E; Barbel, S; Meadows, S A; Jan, L Y; Jan, Y N
The Drosophila adult external sensory organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in sensory organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rorth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external sensory organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external sensory organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external sensory organs or subsets of sensory organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system. PMID:10835395
Sensory profile of a model energy drink with varying levels of functional ingredients-caffeine, ginseng, and taurine.
Tamamoto, Lauren C; Schmidt, Shelly J; Lee, Soo-Yeun
Energy drinks have increased in popularity in recent years due to the claimed energy boost provided by functional ingredients. A multitude of functional ingredients have been utilized; however, there is limited research on their sensory effects in energy drink formulations. A 13-member descriptive analysis panel was conducted to investigate the effects on the sensory and rheological properties of 3 common functional ingredients-caffeine, ginseng, and taurine-in a noncarbonated model energy drink solution. Combinations of these functional ingredients at 3 levels (low, medium, high) were added to create a total of 27 different solutions (3 x 3 x 3 factorial design). Analysis of variance was performed to evaluate the sensory effects of the varying concentrations of functional ingredients in solution. Principal component analysis (PCA) was performed to summarize the relationship among the attributes and solutions. In general, high levels of caffeine in solution resulted in low ratings of fruity attributes and high ratings of bitter tea and fruit bitter attributes. The high level of ginseng in solution was characterized by high ratings of bitter attributes. A horns effect was observed as the sweet, artificial lemon-lime, pear, mango, and pineapple attributes were rated lower in intensity with increased ginseng levels. Taurine levels of up to 416 mg/100 mL had no significant effect on the sensory attribute ratings of the model energy drink solutions. These findings can be utilized to predict the changes in sensory characteristics when formulating energy drinks containing these popular functional ingredients. PMID:20722948
Effect of lycium barbarum (wolfberry) polysaccharides on preserving retinal function after partial optic nerve transection.
Chu, Patrick H W; Li, Hong-Ying; Chin, Man-Pan; So, Kwok-fai; Chan, Henry H L
Lycium Barbarum Polysaccharides (LBP) are the active components of Wolfberry (a traditional Chinese medicine) which has long been used for improving visual function. This study aims to investigate localized changes of retinal function in a partial optic nerve transection (PONT) model, and effects of LBP on visual function. The multifocal electroretinograms (mfERG) were obtained from 30 eyes of 30 Sprague-Dawley rats. The rats were divided into 6 groups (five treatment groups and one control group). Starting from the first day of the experiment, the rats in the (PONT+LBP) group and the (LBP) group were dosed with LBP; rats in the (PONT+PBS (phosphate buffered saline)) group and the (PBS) group were dosed with PBS via nasogastric tube every day until euthanized. The dorsal part of the optic nerve was transected in the (PONT), (PONT+LBP) and (PONT+PBS) groups at the end of week 1 (day 7 after LBP or PBS feeding began). The mfERG was measured at three time points: week 2, week 3 and week 5. Significant reduction of P1 and PhNR amplitudes of the mfERG were observed in all retinal regions a week after PONT. Feeding with LBP prior to PONT preserved retinal function. All mfERG responses returned to the normal range in the superior retina, which corresponds to the transected dorsal region of the optic nerve, while most of the inferior retinal responses were significantly increased at week 4 after PONT. The ventral part of the retina had secondary degeneration which was not only limited to the ganglion cell layer, but is a widespread effect affecting the outer retina. LBP altered the functional reduction caused by PONT by regulating the signal from the outer retina. PMID:24339917
In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration.
Das, Suradip; Sharma, Manav; Saharia, Dhiren; Sarma, Kushal Konwar; Sarma, Monalisa Goswami; Borthakur, Bibhuti Bhusan; Bora, Utpal
We report a novel silk-gold nanocomposite based nerve conduit successfully tested in a neurotmesis grade sciatic nerve injury model in rats over a period of eighteen months. The conduit was fabricated by adsorbing gold nanoparticles onto silk fibres and transforming them into a nanocomposite sheet by electrospinning which is finally given a tubular structure by rolling on a stainless steel mandrel of chosen diameter. The conduits were found to promote adhesion and proliferation of Schwann cells in vitro and did not elicit any toxic or immunogenic responses in vivo. We also report for the first time, the monitoring of muscular regeneration post nerve conduit implantation by recording motor unit potentials (MUPs) through needle electromyogram. Pre-seeding the conduits with Schwann cells enhanced myelination of the regenerated tissue. Histo-morphometric and electrophysiological studies proved that the nanocomposite based conduits pre-seeded with Schwann cells performed best in terms of structural and functional regeneration of severed sciatic nerves. The near normal values of nerve conduction velocity (50 m/sec), compound muscle action potential (29.7 mV) and motor unit potential (133 ?V) exhibited by the animals implanted with Schwann cell loaded nerve conduits in the present study are superior to those observed in previous reports with synthetic materials as well as collagen based nerve conduits. Animals in this group were also able to perform complex locomotory activities like stretching and jumping with excellent sciatic function index (SFI) and led a normal life. PMID:26026910
Functional interactions between tumor and peripheral nerve in a model of cancer pain in the mouse.
Cain, D M; Wacnik, P W; Eikmeier, L; Beitz, A; Wilcox, G L; Simone, D A
Cancer is usually accompanied by pain, which tends to increase in relation to metastatic infiltration and destruction. In the United States, 30% to 40% of newly diagnosed cancer patients and 67% to 90% of patients with advanced cancer report moderate to severe pain. Relief for approximately 90% of patients with cancer-related pain may be provided by the World Health Organization's "analgesic ladder," which involves progressing from non-opioid (e.g., acetaminophen, ibuprofen) to weak opioid (e.g., codeine), to strong opioid (e.g., morphine, fentanyl) intervention for pain relief. The severity of cancer pain is affected by diverse factors. In addition to the obvious factors of tumor size and degree of metastatic destruction, the type of tumor and its location are also important factors that contribute to pain severity. Severe cancer pain is especially associated with tumors involving bone destruction and nerve infiltration. Cancer pain seems to involve diverse mechanisms, including characteristics of both nociceptive and neuropathic pain. Unfortunately, even opioid analgesics often produce poor pain relief against neuropathic pain derived from peripheral nerve or root damage common to cancers involving bone metastases and nerve infiltration. In addition, these drugs may induce adverse side effects since they affect various physiological functions, including hormone secretion, neurotransmitter release, feeding, gastrointestinal motility, and respiratory activity. Currently, drug therapies utilizing antidepressants and anticonvulsants are being used to relieve neuropathic pain whereas cancer pain is treated largely with opiods in cancer patients. PMID:15102313
Biophysical and functional consequences of receptor-mediated nerve fiber transformation.
Tanelian, D L; Markin, V S
Stimulation of the nervous system by substance P, a G protein-coupled receptor, and subsequent receptor internalization causes dendrites to change their shape from homogeneous cylinders to a heterogeneous string of swollen varicosities (beads) connected by thin segments. In this paper we have analyzed this phenomenon and propose quantitative mechanisms to explain this type of physical shape transformation. We developed a mathematical solution to describe the relationship between the initial radius of a cylindrical nerve fiber and the average radii of the subsequently created varicosities and connecting segments, as well as the periodicity of the varicosities along the nerve fiber. Theoretical predictions are in good agreement with our own and published experimental data from dorsal root ganglion neurons, spinal cord, and brain. Modeling the electrical properties of these beaded fibers has led to an understanding of the functional biophysical consequences of nerve fiber transformation. Several hypotheses for how this shape transformation can be used to process information within the nervous system have been put forth. Images FIGURE 1 FIGURE 6 PMID:9138558
Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria
Calupca, Michelle A; Prior, Chris; Merriam, Laura A; Hendricks, Gregory M; Parsons, Rodney L
Presynaptic function was investigated at K+-stimulated motor nerve terminals in snake costocutaneous nerve muscle preparations exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP, 2 ?m), oligomycin (8 ?g ml?1) or CCCP and oligomycin together. Miniature endplate currents (MEPCs) were recorded at -150 mV with two-electrode voltage clamp. With all three drug treatments, during stimulation by elevated K+ (35 mm), MEPC frequencies initially increased to values > 350 s?1, but then declined. The decline occurred more rapidly in preparations treated with CCCP or CCCP and oligomycin together than in those treated with oligomycin alone. Staining with FM1-43 indicated that synaptic vesicle membrane endocytosis occurred at some CCCP- or oligomycin-treated nerve terminals after 120 or 180 min of K+ stimulation, respectively. The addition of glucose to stimulate production of ATP by glycolysis during sustained K+ stimulation attenuated the decline in MEPC frequency and increased the percentage of terminals stained by FM1-43 in preparations exposed to either CCCP or oligomycin. We propose that the decline in K+-stimulated quantal release in preparations treated with CCCP, oligomycin or CCCP and oligomycin together could result from a progressive elevation of intracellular calcium concentration ([Ca2+]i). For oligomycin-treated nerve terminals, a progressive elevation of [Ca2+]i could occur as the cytoplasmic ATP/ADP ratio decreases, causing energy-dependent Ca2+ buffering mechanisms to fail. The decline in MEPC frequency could occur more rapidly in preparations treated with CCCP or CCCP and oligomycin together because mitochondrial Ca2+ buffering and ATP production were both inhibited. Therefore, the proposed sustained elevation of [Ca2+]i could occur more rapidly. PMID:11283236
Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria.
Calupca, M A; Prior, C; Merriam, L A; Hendricks, G M; Parsons, R L
Presynaptic function was investigated at K+-stimulated motor nerve terminals in snake costocutaneous nerve muscle preparations exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP, 2 M), oligomycin (8 g x ml(-1)) or CCCP and oligomycin together. Miniature endplate currents (MEPCs) were recorded at -150 mV with two-electrode voltage clamp. With all three drug treatments, during stimulation by elevated K+ (35 mM), MEPC frequencies initially increased to values > 350 s(-1), but then declined. The decline occurred more rapidly in preparations treated with CCCP or CCCP and oligomycin together than in those treated with oligomycin alone. Staining with FM1-43 indicated that synaptic vesicle membrane endocytosis occurred at some CCCP- or oligomycin-treated nerve terminals after 120 or 180 min of K+ stimulation, respectively. The addition of glucose to stimulate production of ATP by glycolysis during sustained K+ stimulation attenuated the decline in MEPC frequency and increased the percentage of terminals stained by FM1-43 in preparations exposed to either CCCP or oligomycin. We propose that the decline in K+-stimulated quantal release in preparations treated with CCCP, oligomycin or CCCP and oligomycin together could result from a progressive elevation of intracellular calcium concentration ([Ca2+]i). For oligomycin-treated nerve terminals, a progressive elevation of [Ca2+]i could occur as the cytoplasmic ATP/ADP ratio decreases, causing energy-dependent Ca2+ buffering mechanisms to fail. The decline in MEPC frequency could occur more rapidly in preparations treated with CCCP or CCCP and oligomycin together because mitochondrial Ca2+ buffering and ATP production were both inhibited. Therefore, the proposed sustained elevation of [Ca2+]i could occur more rapidly. PMID:11283236
Fluorescence microscopic morphometry of functioning blood vessels and adrenergic nerves in myocardium.
Muntz, K H; Hagler, H K; Boulas, H J; Buja, L M
The purpose of this study was to quantify the percent volume of actively functioning blood vessels in five dogs subjected to ligation of the left anterior descending artery and to localize catecholamine-containing nerve terminals in the same tissue blocks. Radioactive microspheres were injected to determine the extent of flow reduction in the ischemic zone. After 1 or 3 hr of occlusion, thioflavin-S (0.125 ml/Kg of a 4% solution) was injected intravenously 15 sec prior to removal of the heart. Tissue samples were reacted with paraformaldehyde to visualize catecholamine-containing nerve terminals prior to embedding in paraffin. The percent volume of blood vessels labeled with thioflavin-S was quantitated in tissue sections using a point-counting technique in which a small dot from a video screen was projected through an image-projecting tube and moved by computer control over the image of the fluorescent tissue. In the nonischemic zone, the mean blood flow determined by the microsphere technique was 1.29 ml/min/g +/- 0.48 (SD), and the mean volume percent of thioflavin-labeled vessels was 12.67 +/- 3.30. In the ischemic and border zone areas, there was wide range of flow reduction, and there was a significant correlation between the blood flow measured with microspheres and the percent volume of thioflavin-labeled blood vessels (R = 0.80, P less than 0.001). In the nonischemic zone, both blood vessels and catecholamine-containing nerve terminals were visible; however, in the ischemic zone, few labeled vessels were seen, although nerve terminals were often present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6711839
Metathoracic neurons integrating intersegmental sensory information in the locust.
Matheson, Tom
This paper describes the morphology and physiology of five types of local interneurons and three types of ascending intersegmental interneurons in the locust metathoracic ganglion that are points of convergence of sensory information from the wings. Four types of spiking local interneurons are members of a population with somata at the ventral midline. They are depolarised by stimulation of a metathoracic wing nerve, suggesting that they encode a sensory representation of this appendage. Some are also depolarised with short latencies following stimulation of a mesothoracic wing nerve, indicating that they collate intersegmental as well as local information. All the local interneurons have branches in the anterior ventral association centre or around the roots of the nerve that carries wing sensory neurons. This distinguishes them from other interneurons in the population. A fifth type of local interneuron that has unusual bilateral branching and is not a member of this population is described for the first time. The ascending interneurons are members of three populations. Neurons of each population have a characteristic pattern of responses to stimulation of the mesothoracic or metathoracic wing nerves, and some respond to tactile stimulation or movements of a hind leg. These latter interneurons thus collate information from both wings and legs. All three types of intersegmental interneurons have branches in the anterior ventral association centre or around the roots of the wing nerve. The responses of the interneurons described here shed new light on both local and intersegmental network function in this model system. PMID:11835184
Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors
Xavier Grosmaitre; Lindsey C Santarelli; Jie Tan; Minmin Luo; Minghong Ma
Most sensory systems are primarily specialized to detect one sensory modality. Here we report that olfactory sensory neurons (OSNs) in the mammalian nose can detect two distinct modalities transmitted by chemical and mechanical stimuli. As revealed by patch-clamp recordings, many OSNs respond not only to odorants, but also to mechanical stimuli delivered by pressure ejections of odor-free Ringer solution. The
Repair of peripheral nerve with vein wrapping*
Objective The post–traumatic neuro-anastomosis must be protected from the surrounding environment. This barrier must be biologically inert, biodegradable, not compressing but protecting the nerve. Formation of painful neuroma is one of the major issues with neuro-anastomosis; currently there is no consensus on post-repair neuroma prevention. Aim of this study is to evaluate the efficacy of neuroanastomosis performed with venous sheath to reduce painful neuromas formation, improve the electrical conductivity of the repaired nerve, and reduce the discrepancies of the sectioned nerve stumps. Patients and methods From a trauma population of 320 patients treated in a single centre between January 2008 and December 2011, twenty-six patients were identified as having an injury to at least one of the peripheral nerves of the arm and enrolled in the study. Patients were divided into two groups. In the group A (16 patients) the end-to-end nerve suture was wrapped in a vein sheath and compared with the group B (10 patients) in which a simple end-to-end neurorrhaphy was performed. The venous segment used to cover the nerve micro-suture was harvested from the superficial veins of the forearm. The parameters analyzed were: functional recovery of motor nerves, sensitivity and pain. Results Average follow-up was 14 months (range: 12–24 months). The group A showed a more rapid motor and sensory recovery and a reduction of the painful symptoms compared to the control group (B). Conclusions The Authors demonstrated that, in their experience, the venous sheath provides a valid solution to avoid the dispersion of the nerve fibres, to prevent adherent scars and painful neuromas formation. Moreover it can compensate the different size of two nerve stumps, allowing, thereby, a more rapid functional and sensitive recovery without expensive devices. PMID:24841688
Sensory interaction with central 'generators' during respiration in the dogfish
B. L. Roberts; C. M. Ballintijn
Summary The activity in sensory and motor nerves of the gills was recorded from selected branches of the vagus nerve in decerebrate dogfish,Scyliorhinus canicula. Vagal motoneuronal activity was observed at the start of the rapid pharyngeal contraction and was followed by sensory nerve activity which preceded the slow expansion phase. Rhythmical vagal motoneuronal activity was still present after all movements
Influence of putrescine and carnauba wax on functional and sensory quality of pomegranate (Punica granatum L.) fruits during storage.
Barman, Kalyan; Asrey, Ram; Pal, R K; Kaur, Charanjit; Jha, S K
Functional properties (anthocyanins, antioxidant, ascorbic acid and tannin) and sensory score were determined in pomegranate fruits at two storage temperatures (3 and 5 °C) after treatment with 2 mM putrescine and 1 : 10 carnauba wax (carnauba wax : water). The treatments (putrescine and carnauba wax) were given by immersion method followed by storage up to 60 days. Both treatments retained significantly higher anthocyanins, antioxidant, ascorbic acid, tannin and sensory qualities as compared with control fruits under both the storage conditions. Combined application of putrescine + carnauba wax showed better response in retaining functional properties than putrescine treated or nontreated fruits. The impacts of putrescine and carnauba wax treatments were found more pronounced after 30 days at 3-5 °C storage temperature in retaining functional and sensory qualities. After 60 days of storage, putrescine + carnauba wax retained about 25% higher antioxidant activity both at 3 and 5 °C storage temperatures. PMID:24426055
PurposeBotulinum neurotoxin type A (BoNT\\/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT\\/A may affect sensory fibers. We investigated a possible effect of BoNT\\/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1
Drosophila Notch receptor activity suppresses Hairless function during adult external sensory organ development.
Lyman, D F; Yedvobnick, B
The neurogenic Notch locus of Drosophila encodes a receptor necessary for cell fate decisions within equivalence groups, such as proneural clusters. Specification of alternate fates within clusters results from inhibitory communication among cells having comparable neural fate potential. Genetically, Hairless (H) acts as an antagonist of most neurogenic genes and may insulate neural precursor cells from inhibition. H function is required for commitment to the bristle sensory organ precursor (SOP) cell fate and for daughter cell fates. Using Notch gain-of-function alleles and conditional expression of an activated Notch transgene, we show that enhanced signaling produces H-like loss-of-function phenotypes by suppressing bristle SOP cell specification or by causing an H-like transformation of sensillum daughter cell fates. Furthermore, adults carrying Notch gain of function and H alleles exhibit synergistic enhancement of mutant phenotypes. Over-expression of an H+ transgene product suppressed virtually all phenotypes generated by Notch gain-of-function genotypes. Phenotypes resulting from over-expression of the H+ transgene were blocked by the Notch gain-of-function products, indicating a balance between Notch and H activity. The results suggest that H insulates SOP cells from inhibition and indicate that H activity is suppressed by Notch signaling. PMID:8601489
Glaucoma Progression Detection Using Structural Retinal Nerve Fiber Layer Measurements and Functional Visual Field Points
Yousefi, Siamak; Goldbaum, Michael H.; Balasubramanian, Madhusudhanan; Jung, Tzyy-Ping; Weinreb, Robert N.; Medeiros, Felipe A.; Zangwill, Linda M.; Liebmann, Jeffrey M.; Girkin, Christopher A.
Machine learning classifiers were employed to detect glaucomatous progression using longitudinal series of structural data extracted from retinal nerve fiber layer thickness measurements and visual functional data recorded from standard automated perimetry tests. Using the collected data, a longitudinal feature vector was created for each patient's eye by computing the norm 1 difference vector of the data at the baseline and at each follow-up visit. The longitudinal features from each patient's eye were then fed to the machine learning classifier to classify each eye as stable or progressed over time. This study was performed using several machine learning classifiers including Bayesian, Lazy, Meta, and Tree, composing different families. Combinations of structural and functional features were selected and ranked to determine the relative effectiveness of each feature. Finally, the outcomes of the classifiers were assessed by several performance metrics and the effectiveness of structural and functional features were analyzed. PMID:24658239
Neuronal porosome - The secretory portal at the nerve terminal: Its structure-function, composition, and reconstitution
NASA Astrophysics Data System (ADS)
Jena, Bhanu P.
Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate secretion from cells. Membrane bound secretory vesicles transiently dock and fuse at the cytosolic compartment of the porosome base to expel intravesicular contents to the outside during cell secretion. In the past decade, the structure, isolation, composition, and functional reconstitution of the neuronal porosome complex has been accomplished providing a molecular understanding of its structure-function. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins; compared to the 120 nm nuclear pore complex comprised of over 500 protein molecules composed of 30 different proteins. Being a membrane-associated supramolecular complex has precluded determination of the atomic structure of the porosome. However recent studies using small-angle X-ray solution scattering (SAXS), provide at sub-nanometer resolution, the native 3D structure of the neuronal porosome complex associated with docked synaptic vesicle at the nerve terminal. Additionally, results from the SAXS study and earlier studies using atomic force microscopy, provide the possible molecular mechanism involved in porosome-mediated neurotransmitter release at the nerve terminal.
Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.
Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D
Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940
Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats
Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055
5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation.
Darios, Emma S; Barman, Susan M; Orer, Hakan S; Morrison, Shaun F; Davis, Robert P; Seitz, Bridget M; Burnett, Robert; Watts, Stephanie W
Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25?g/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865
Short?term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats.
Li, Yan; Xuan, Yan-Hua; Liu, Shuang-Shuang; Dong, Jing; Luo, Jia-Ying; Sun, Zhi-Jun
Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long?term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short?term VNS on the hemodynamics of cardiac remodeling and cardiac excitation?contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham?stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055
Nerve Regeneration After Radiofrequency Application
Nobuyasu Ochiai; James P. Tasto; Seiji Ohtori; Norimasa Takahashi; Hideshige Moriya; David Amiel
Background: Many patients with chronic tendinosis have experienced early pain relief after application of bipolar radiofrequency treatment. It is hypothesized that the mechanism of action may be the acute degeneration and\\/or ablation of sensory nerve fibers. Hypothesis: After ablation or degeneration by bipolar radiofrequency, nerve fibers will have the ability to regenerate with time. Study Design: Controlled laboratory study. Methods:
Effects of polysialic acid on sensory innervation of the cornea.
Mao, Xiuli; Zhang, Yuntao; Schwend, Tyler; Conrad, Gary W
Sensory trigeminal growth cones innervate the cornea in a coordinated fashion during embryonic development. Polysialic acid (polySia) is known for its important roles during nerve development and regeneration. The purpose of this work is to determine whether polySia, present in developing eyefronts and on the surface of sensory nerves, may provide guidance cues to nerves during corneal innervation. Expression and localization of polySia in embryonic day (E)5-14 chick eyefronts and E9 trigeminal ganglia were identified using Western blotting and immunostaining. Effects of polySia removal on trigeminal nerve growth behavior were determined in vivo, using exogenous endoneuraminidase (endoN) treatments to remove polySia substrates during chick cornea development, and in vitro, using neuronal explant cultures. PolySia substrates, made by the physical adsorption of colominic acid to a surface coated with poly-d-lysine (PDL), were used as a model to investigate functions of the polySia expressed in axonal environments. PolySia was localized within developing eyefronts and on trigeminal sensory nerves. Distributions of PolySia in corneas and pericorneal regions are developmentally regulated. PolySia removal caused defasciculation of the limbal nerve trunk in vivo from E7 to E10. Removal of polySia on trigeminal neurites inhibited neurite outgrowth and caused axon defasciculation, but did not affect Neural Cell Adhesion Molecule (NCAM) expression or Schwann cell migration in vitro. PolySia substrates in vitro inhibited outgrowth of trigeminal neurites and promoted their fasciculation. In conclusion, polySia is localized on corneal nerves and in their targeting environment during early developing stages of chick embryos. PolySias promote fasciculation of trigeminal axons in vivo and in vitro, whereas, in contrast, their removal promotes defasciculation. PMID:25478909
Effects of Electroacupuncture on Facial Nerve Function and HSV-1 DNA Quantity in HSV-1 Induced Facial Nerve Palsy Mice
Tang, Hongzhi; Feng, Shuwei; Chen, Jiao; Yang, Mingxiao; Zhong, Zhendong; Li, Ying; Liang, Fanrong
Acupuncture is a common and effective therapeutic method to treat facial nerve palsy (FNP). However, its underlying mechanism remains unclear. This study was aimed to investigate the effects of electroacupuncture on symptoms and content of HSV-1 DNA in FNP mice. Mice were randomized into four groups, an electroacupuncture treatment group, saline group, model animal group, and blank control group. Electroacupuncture was applied at Jiache (ST6) and Hegu (LI4) in electroacupuncture group once daily for 14 days, while electroacupuncture was not applied in model animal group. In electroacupuncture group, mice recovered more rapidly and HSV-1 DNA content also decreased more rapidly, compared with model animal group. We conclude that electroacupuncture is effective to alleviate symptoms and promote the reduction of HSV-1 in FNP. PMID:24991226
Sensory profiling and hedonic judgement of probiotic ice cream as a function of hydrocolloids, yogurt and milk fat content
Christos Soukoulis; Eleni Lyroni; Constantina Tzia
Probiotic ice cream is a functional frozen dairy dessert with peculiar sensory characteristics combining the flavor and taste of fermented milks with the texture of ice cream. In this study, the effects of compositional parameters (hydrocolloids type and percentage, yogurt and milk fat content) on its texture and flavor were evaluated. The use of xanthan gum or hydroxypropylmethylcellulose at a
Changes in nutritional composition, functional, and sensory properties of yam flour as a result of presoaking
Obadina, Adewale Olusegun; Babatunde, Bukunola Olaide; Olotu, Ifeoluwa
This study investigated the effect of soaking pretreatments on some of the properties of flour obtained from two varieties of yam namely;Dioscorea alata andDioscorea rotundata with a view of providing information that will enhance their end use. The yam varieties were washed, chipped, parboiled at 50°C, soaked for different periods (0, 6, 12, and 18 h), dried at 60°C, and milled into flour. The flour samples were analyzed for their nutritional composition, pH, color, and functional properties. The flour samples were also made into pastes and were sensorially analyzed and 0 h soaked samples were used as control. The protein content of 18 h-soakedD. rotundata andD. alata flour samples was significantly different from the control and soaking had no effect (P > 0.05) on the fat and ash content but the carbohydrate content of the flour samples ranged from 83.08% to 86.13%. The 18 h-soakedD. rotundata flour sample had the lowest peak viscosity, breakdown value, and final viscosity among theD. rotundata variety samples. Pasting temperature ranged from 79.80 to 83.60°C and 6-h soakedD. alata flour sample had the lowest water absorption capacity and the highest bulk density. On the basis of sensory analysis, the panelist preferred the taste, texture, color, and appearance of paste made from the 18-h soakedD. rotundata flour to the paste of other flour samples. The results of this study show that D.rotundata should be soaked for 18 h prior to drying and milling in order to obtain a good-quality flour and paste. PMID:25493185
Local administration of icariin contributes to peripheral nerve regeneration and functional recovery
Chen, Bo; Niu, Su-ping; Wang, Zhi-yong; Wang, Zhen-wei; Deng, Jiu-xu; Zhang, Pei-xun; Yin, Xiao-feng; Han, Na; Kou, Yu-hui; Jiang, Bao-guo
Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the therapeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly(lactic-co-glycolic acid) biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local application of icariin after spinal injury can promote peripheral nerve regeneration. PMID:25788925
Local administration of icariin contributes to peripheral nerve regeneration and functional recovery.
Chen, Bo; Niu, Su-Ping; Wang, Zhi-Yong; Wang, Zhen-Wei; Deng, Jiu-Xu; Zhang, Pei-Xun; Yin, Xiao-Feng; Han, Na; Kou, Yu-Hui; Jiang, Bao-Guo
Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the therapeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly(lactic-co-glycolic acid) biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local application of icariin after spinal injury can promote peripheral nerve regeneration. PMID:25788925
BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors.
Xu, Qingwen; Zhang, Yuxia; Wei, Qing; Huang, Yan; Li, Yan; Ling, Kun; Hu, Jinghua
Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS-4 and BBS-5, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS-4 directly interacts with BBS-5 and the interaction can be disrupted by a conserved mutation identified in human BBS4. Surprisingly, we found that BBS-4 and BBS-5 act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co-depletion of BBS-4 and BBS-5 disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS4 and BBS5 also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation. PMID:26150102
BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors
Xu, Qingwen; Zhang, Yuxia; Wei, Qing; Huang, Yan; Li, Yan; Ling, Kun; Hu, Jinghua
Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS-4 and BBS-5, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS-4 directly interacts with BBS-5 and the interaction can be disrupted by a conserved mutation identified in human BBS4. Surprisingly, we found that BBS-4 and BBS-5 act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co-depletion of BBS-4 and BBS-5 disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS4 and BBS5 also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation. PMID:26150102
Functional selectivity and time-dependence of ?-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area
Lowe, J D; Bailey, C P
BACKGROUND AND PURPOSE The majority of studies examining desensitization of the ?-opioid receptor (MOR) have examined those located at cell bodies. However, MORs are extensively expressed at nerve terminals throughout the mammalian nervous system. This study is designed to investigate agonist-induced MOR desensitization at nerve terminals in the mouse ventral tegmental area (VTA). EXPERIMENTAL APPROACH MOR function was measured in mature mouse brain slices containing the VTA using whole-cell patch-clamp electrophysiology. Presynaptic MOR function was isolated from postsynaptic function and the functional selectivity, time-dependence and mechanisms of agonist-induced MOR desensitization were examined. KEY RESULTS MORs located at GABAergic nerve terminals in the VTA were completely resistant to rapid desensitization induced by the high-efficacy agonists DAMGO and Met-enkephalin. MORs located postsynaptically on GABAergic cell bodies readily underwent rapid desensitization in response to DAMGO. However, after prolonged (>7 h) treatment with Met-enkephalin, profound homologous MOR desensitization was observed. Morphine could induce rapid MOR desensitization at nerve terminals when PKC was activated. CONCLUSIONS AND IMPLICATIONS Agonist-induced MOR desensitization in GABAergic neurons in the VTA is compartment-selective as well as agonist-selective. When MORs are located at cell bodies, higher-efficacy agonists induce greater levels of rapid desensitization than lower-efficacy agonists. However, the converse is true at nerve terminals where agonists that induce MOR desensitization via PKC are capable of rapid agonist-induced desensitization while higher-efficacy agonists are not. MOR desensitization induced by higher-efficacy agonists at nerve terminals only takes place after prolonged receptor activation. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24467517
A Functional Interpretation of the Electron-Microscopic Structure of the Sensory Hairs in the Cristć of the Elasmobranch Raja clavata in Terms of Directional Sensitivity
O. Lowenstein; J. WERSÄLL
THE sensory cells in the vertebrate labyrinth are epithelial cells innervated by end-branches of bipolar neurons of the various first-order ganglia associated with the 8th cranial nerve. Physiologically, the response behaviour of these cells has been thoroughly analysed in the semi-circular canals and otolith organs of the labyrinth of the elasmobranch fish, Raja clavata1-3 and of the frog4.
Genetics Home Reference: Hereditary sensory and autonomic neuropathy type V
... to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ... gene ; growth factor ; hereditary ; inherited ; joint ; mutation ; neuropathy ; perception ; protein ; receptor ; recessive ; sensory nerve ; sensory neuropathy ; tissue ; ...
Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings
Luba Kalaydjieva; Amelia Nikolova; Ivo Turnev; Julia Petrova; Anna Hristova; Boryana Ishpekova; Iva Petkova; Alexander Shmarov; Stella Stancheva; L. Middleton; Luciano Merlini; A. Trogu; J. R. Muddle; R. H. M. King; P. K. Thomas
Summary A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait
Channels active in the excitability of nerves and skeletal muscles across the neuromuscular junction: basic function and pathophysiology
NSDL National Science Digital Library
PhD Barbara E. Goodman (University of South Dakota School of Medicine Division of Basic Biomedical Sciences)
Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the activation of motoneurons and their corresponding muscle cells is essential for interpreting basic neurophysiology in nerves, the heart, and skeletal and smooth muscle. This review article is intended to clarify how channels work in nerves, neuromuscular junctions, and muscle function and what happens when these channels are defective. Highlighting the human diseases that result from defective ion channels is likely to be interesting to students in helping them choose to learn about channel physiology.
Effect of developmental sensory and motor deprivation on the functional organization of adult rat somatosensory cortex
Irina A. Erchova; Rasmus S. Petersen; Mathew E. Diamond
Most sensory systems are active, in the sense that the animal performs specific motor actions in order to collect information of interest—signals are not merely passively received. We, therefore, expect cortical development to depend not only correct sensory experience, but also on correct motor experience. In this study, we used the rat whisker system as a model to compare the
Sernaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord
Elizabeth K Messersmith; E. David Leonardo; Carla J Shatz; Marc Tessier-Lavigne; Corey S Goodman; Alex L Kolodkin
Distinct classes of primary sensory neurons in dorsal root ganglia subserve different sensory modalities, terminate in different dorsoventral locations in the spinal cord, and display different neurotrophin response profiles. Large diameter muscle afferents that terminate in the ventral spinal cord are NT-3 responsive, whereas small diameter afferents subserving pain and temperature are NGF responsive and terminate in the dorsal spinal
Near infrared (NIr) light increases expression of a marker of mitochondrial function in the mouse vestibular sensory epithelium.
Zhang, Lucy; Tung, Victoria W K; Mathews, Miranda; Camp, Aaron J
Strategies for attenuating decline in balance function with increasing age are predominantly focused on physical therapies including balance tasks and exercise. However, these approaches do not address the underlying causes of balance decline. Using mice, the impact of near infrared light (NIr) on the metabolism of cells in the vestibular sensory epithelium was assessed. Data collected shows that this simple and safe intervention may protect these vulnerable cells from the deleterious effects of natural aging. mRNA was extracted from the isolated peripheral vestibular sensory epithelium (crista ampullaris and utricular macula) and subsequently transcribed into a cDNA library. This library was then probed for the expression of ubiquitous antioxidant (SOD-1). Antioxidant gene expression was then used to quantify cellular metabolism. Using transcranial delivery of NIr in young (4 weeks) and older (8-9 months) mice, and a brief treatment regime (90 sec/day for 5 days), this work suggests NIr alone may be sufficient to improve mitochondrial function in the vestibular sensory epithelium. Since there are currently no available, affordable, non-invasive methods of therapy to improve vestibular hair cell function, the application of external NIr radiation provides a potential strategy to counteract the impact of aging on cellular metabolism inthe vestibular sensory epithelium. PMID:25868009
Prevention of NKCC1 phosphorylation avoids downregulation of KCC2 in central sensory pathways and reduces neuropathic pain after peripheral nerve injury.
Mňdol, Laura; Cobianchi, Stefano; Navarro, Xavier
Neuropathic pain after peripheral nerve injury is characterized by loss of inhibition in both peripheral and central pain pathways. In the adult nervous system, the Na(+)-K(+)-2Cl(-) (NKCC1) and neuron-specific K(+)-Cl(-) (KCC2) cotransporters are involved in setting the strength and polarity of GABAergic/glycinergic transmission. After nerve injury, the balance between these cotransporters changes, leading to a decrease in the inhibitory tone. However, the role that NKCC1 and KCC2 play in pain-processing brain areas is unknown. Our goal was to study the effects of peripheral nerve injury on NKCC1 and KCC2 expression in dorsal root ganglia (DRG), spinal cord, ventral posterolateral (VPL) nucleus of the thalamus, and primary somatosensory (S1) cortex. After sciatic nerve section and suture in adult rats, assessment of mechanical and thermal pain thresholds showed evidence of hyperalgesia during the following 2 months. We also found an increase in NKCC1 expression in the DRG and a downregulation of KCC2 in spinal cord after injury, accompanied by later decrease of KCC2 levels in higher projection areas (VPL and S1) from 2 weeks postinjury, correlating with neuropathic pain signs. Administration of bumetanide (30 mg/kg) during 2 weeks following sciatic nerve lesion prevented the previously observed changes in the spinothalamic tract projecting areas and the appearance of hyperalgesia. In conclusion, the present results indicate that changes in NKCC1 and KCC2 in DRG, spinal cord, and central pain areas may contribute to development of neuropathic pain. PMID:24813295
Cranial and Spinal Nerve Organization in Amphioxus and Lampreys: Evidence for an Ancestral Craniate Pattern
B. Fritzsch; Glenn Northcutt
The spinal nerves in amphioxus are compared with the spinal and cranial nerves in lampreys. The dorsal spinal roots in amphioxus are similar to the mixed sensory and motor dorsal roots of many cranial nerves in lampreys but not to the purely sensory dorsal spinal roots in lampreys and gnathostomes. Likewise, cranial nerves V, VII, IX and X in lampreys,
Communication between neuronal somata and satellite glial cells in sensory ganglia.
Huang, Li-Yen M; Gu, Yanping; Chen, Yong
Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. "What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia?" and "how do tissue or nerve injuries affect the communication?" are the main questions addressed in this review. PMID:23918214
Engineering Peripheral Nerve Repair
Marquardt, Laura; Sakiyama-Elbert, Shelly E.
Current approaches for treating peripheral nerve injury have resulted in promising, yet insufficient functional recovery compared to the clinical standard of care, autologous nerve grafts. In order to design a construct that can match the regenerative potential of the autograft, all facets of nerve tissue must be incorporated in a combinatorial therapy. Engineered biomaterial scaffolds in the future will have to promote enhanced regeneration and appropriate reinnervation by targeting the highly sensitive response of regenerating nerves to their surrounding microenvironment. PMID:23790730
High lead exposure and auditory sensory-neural function in Andean children.
Counter, S A; Vahter, M; Laurell, G; Buchanan, L H; Ortega, F; Skerfving, S
We investigated blood lead (B-Pb) and mercury (B-Hg) levels and auditory sensory-neural function in 62 Andean school children living in a Pb-contaminated area of Ecuador and 14 children in a neighboring gold mining area with no known Pb exposure. The median B-Pb level for 62 children in the Pb-exposed group was 52.6 micrograms/dl (range 9.9-110.0 micrograms/dl) compared with 6.4 micrograms/dl (range 3.9-12.0 micrograms/dl) for the children in the non-Pb exposed group; the differences were statistically significant (p < 0.001). Auditory thresholds for the Pb-exposed group were normal at the pure tone frequencies of 0.25-8 kHz over the entire range of B-Pb levels, Auditory brain stem response tests in seven children with high B-Pb levels showed normal absolute peak and interpeak latencies. The median B-Hg levels were 0.16 micrograms/dl (range 0.04-0.58 micrograms/dl) for children in the Pb-exposed group and 0.22 micrograms/dl (range 0.1-0.44 micrograms/dl) for children in the non-Pb exposed gold mining area, and showed no significant relationship to auditory function. Images Figure 1. Figure 3. A Figure 3. B PMID:9222138
Physiological, Sensory, and Functional Measures in a Model of Wrist Muscle Injury and Recovery
Brown, Lindsay; Brant, Aron; Enns, Deborah; Bryden, Pamela J.
ABSTRACT Purpose: To evaluate the effectiveness of muscle rehabilitation modalities, it is first necessary to develop a model to test measures that would assess physiological, sensory, and functional muscle recovery. This study attempted to develop such a model for wrist injury. Subjects: Healthy male and female adults (n = 25). Methods: Subjects performed wrist muscle damage assessment, soreness, discomfort, difficulty, and functional motor task tests before and 1, 2, and 7 days after eccentric wrist muscle contractions. Wrist-related motor task tests, including the perception of discomfort and difficulty during performance, were also conducted. Results: At 24 hours post–eccentric exercises, wrist extension and flexion force declined (p < 0.05) and soreness (p < 0.05) and circumference (p < 0.05) increased; all returned to normal by 7 days post-exercise. At 24 and 48 hours post-exercise, perception of discomfort and difficulty was elevated during performance of motor tasks (p < 0.05). The completion speed of motor tasks was unaffected at any time post–eccentric exercise (p > 0.05). Conclusions: Loss of wrist muscle force, increased soreness, task discomfort, and difficulty were noted following eccentric exercise. However, subjects appeared able to compensate, such that the speed of completion of motor tasks was not slowed. Longer or more specific motor tasks may be necessary to mimic real work performance decrement and recovery. PMID:20145740
Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain.
Koyama, Minoru; Kinkhabwala, Amina; Satou, Chie; Higashijima, Shin-ichi; Fetcho, Joseph
The hindbrain of larval zebrafish contains a relatively simple ground plan in which the neurons throughout it are arranged into stripes that represent broad neuronal classes that differ in transmitter identity, morphology, and transcription factor expression. Within the stripes, neurons are stacked continuously according to age as well as structural and functional properties, such as axonal extent, input resistance, and the speed at which they are recruited during movements. Here we address the question of how particular networks among the many different sensory-motor networks in hindbrain arise from such an orderly plan. We use a combination of transgenic lines and pairwise patch recording to identify excitatory and inhibitory interneurons in the hindbrain network for escape behaviors initiated by the Mauthner cell. We map this network onto the ground plan to show that an individual hindbrain network is built by drawing components in predictable ways from the underlying broad patterning of cell types stacked within stripes according to their age and structural and functional properties. Many different specialized hindbrain networks may arise similarly from a simple early patterning. PMID:21199937
Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain
Koyama, Minoru; Kinkhabwala, Amina; Satou, Chie; Higashijima, Shin-ichi; Fetcho, Joseph
The hindbrain of larval zebrafish contains a relatively simple ground plan in which the neurons throughout it are arranged into stripes that represent broad neuronal classes that differ in transmitter identity, morphology, and transcription factor expression. Within the stripes, neurons are stacked continuously according to age as well as structural and functional properties, such as axonal extent, input resistance, and the speed at which they are recruited during movements. Here we address the question of how particular networks among the many different sensory-motor networks in hindbrain arise from such an orderly plan. We use a combination of transgenic lines and pairwise patch recording to identify excitatory and inhibitory interneurons in the hindbrain network for escape behaviors initiated by the Mauthner cell. We map this network onto the ground plan to show that an individual hindbrain network is built by drawing components in predictable ways from the underlying broad patterning of cell types stacked within stripes according to their age and structural and functional properties. Many different specialized hindbrain networks may arise similarly from a simple early patterning. PMID:21199937
Results of nerve transfer techniques for restoration of shoulder and elbow function in the context of a meta-analysis of the English literature
Gregory A Merrell; Kimberly A Barrie; David L Katz; Scott W Wolfe
We report the results of 15 patients who underwent nerve transfer for restoration of shoulder and elbow function at our institution for traumatic brachial plexus palsy. We present these results in the context of a meta-analysis of the English literature, designed to quantitatively assess the efficacy of individual nerve transfers for restoration of elbow and shoulder function in a large
Engineering a multimodal nerve conduit for repair of injured peripheral nerve.
Quigley, A F; Bulluss, K J; Kyratzis, I L B; Gilmore, K; Mysore, T; Schirmer, K S U; Kennedy, E L; O'Shea, M; Truong, Y B; Edwards, S L; Peeters, G; Herwig, P; Razal, J M; Campbell, T E; Lowes, K N; Higgins, M J; Moulton, S E; Murphy, M A; Cook, M J; Clark, G M; Wallace, G G; Kapsa, R M I
Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair. PMID:23283383
Engineering a multimodal nerve conduit for repair of injured peripheral nerve
NASA Astrophysics Data System (ADS)
Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.
Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.
Signals and noise in the octavolateralis systems: what is the impact of human activities on fish sensory function?
Braun, Christopher B
The octavolateralis systems of fishes include the vestibular, auditory, lateral line and electrosensory systems. They are united by common developmental and neuro-computational features, including hair cell sensors and computations based on cross-neuron analyses of differential hair cell stimulation patterns. These systems also all use both spectral and temporal filters to separate signals from each other and from noise, and the distributed senses (lateral line and electroreception) add spatial filters as well. Like all sensory systems, these sensors must provide the animal with guidance for adaptive behavior within a sensory scene composed of multiple stimuli and varying levels of ambient noise, including that created by human activities. In the extreme, anthropogenic activities impact the octavolateralis systems by destroying or degrading the habitats that provide ecological resources and sensory inputs. At slightly lesser levels of effect, anthropogenic pollutants can be damaging to fish tissues, with sensory organs often the most vulnerable. The exposed sensory cells of the lateral line and electrosensory systems are especially sensitive to aquatic pollution. At still lesser levels of impact, anthropogenic activities can act as both acute and chronic stressors, activating hormonal changes that may affect behavioral and sensory function. Finally, human activities are now a nearly ubiquitous presence in aquatic habitats, often with no obvious effects on the animals exposed to them. Ship noise, indigenous and industrial fishing techniques, and all the ancillary noises of human civilization form a major part of the soundscape of fishes. How fish use these new sources of information about their habitat is a new and burgeoning field of study. PMID:24920543
Age effect on far field potentials from the brain stem after transcutaneous vagus nerve stimulation
Andreas J. Fallgatter; Ann-Christine Ehlis; Thomas M. Ringel; Martin J. Herrmann
Recently, a new electrophysiological method for the assessment of vagus nerve function in the brainstem has been proposed in healthy participants. Before this procedure may be applied to patients with neurodegenerative diseases, its feasibility in elderly healthy participants and a possible age effect on the measurement have to be investigated. The vagus sensory evoked potentials (VSEP) after transcutaneous electric stimulation
An improved model for the rate-level functions of auditory-nerve fibers.
Heil, Peter; Neubauer, Heinrich; Irvine, Dexter R F
Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Here we reexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate-level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate-level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate-level functions and the Ca(2+) dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca(2+) concentrations at the individual active zones of IHCs. We argue that the Hill coefficient might reflect the intrinsic, biochemical Ca(2+) cooperativity of the Ca(2+) sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds. PMID:22031889
Channels Active in the Excitability of Nerves and Skeletal Muscles across the Neuromuscular Junction: Basic Function and Pathophysiology
ERIC Educational Resources Information Center
Goodman, Barbara E.
Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the…
Estimation of the neuromotor system functional state after sciatic nerve neurorrhaphy in experimental conditions of intravenous laser irradiation of blood
N. I. Nechipurenko; Leonid V. Tanin; Ignatii P. Antonov; Lyudmila A. Vasilevskaya; P. A. Vlasyuk
The speckle-optical methods and the methods of electroneuromyography were used to study the myotonus, the contractional activity of leg muscles and the neuromotor system functional state in intact rabbits and 3 months after the sciatic nerve (SN) neurorrhaphy in conditions of intravenous laser irradiation of blood (ILIB). The blood of animals was exposed to laser radiation with the help of
Evolution of motor and sensory deficits in amyotrophic lateral sclerosis estimated by neurophysiological techniques.
Theys, P A; Peeters, E; Robberecht, W
Although amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motor neurons, there is evidence that the disease can affect other systems, including the sensory system. On the other hand, within the motor neuron pool there is possibly a predilection of the degenerative process for the motor neurons fibers with the fastest conduction velocity (MNFCV). We studied these two aspects of the disease in a group of 50 patients by prospectively assessing several sensory indices and by studying the selectivity of the spinal motor neuron loss. At baseline, nerve conduction studies and somatosensory evoked potentials showed abnormal slowing in the peripheral and central sensory pathways. Thermal thresholds for heating were elevated but were normal for cooling. In more than 60% of the patients at least one of the sensory tests studied was abnormal. However, except for a significant decrease in the amplitude of the sensory nerve action potentials of the sural nerves, these afferent dysfunctions were not progressive over the follow-up period of 6 months, in contrast to the marked deterioration in motor functions. Three different statistical models were applied to evaluate the presence of demyelination, selective loss of MNFCV, or the purely random degeneration of fast- and slow-conducting motor neurons. These data indicate a selective loss of the MNFCV and suggest that subclinical abnormalities of the sensory system in ALS are often present but almost nonprogressive. Furthermore, the amyotrophic lateral sclerosis disease process seems preferentially to affect MNFCV. PMID:10431767
Function-Triggering Antibodies to the Adhesion Molecule L1 Enhance Recovery after Injury of the Adult Mouse Femoral Nerve
Guseva, Daria; Loers, Gabriele; Schachner, Melitta
L1 is among the few adhesion molecules that favors repair after trauma in the adult central nervous system of vertebrates by promoting neuritogenesis and neuronal survival, among other beneficial features. In the peripheral nervous system, L1 is up-regulated in Schwann cells and regrowing axons after nerve damage, but the functional consequences of this expression remain unclear. Our previous study of L1-deficient mice in a femoral nerve injury model showed an unexpected improved functional recovery, attenuated motoneuronal cell death, and enhanced Schwann cell proliferation, being attributed to the persistent synthesis of neurotrophic factors. On the other hand, transgenic mice over-expressing L1 in neurons led to improved remyelination, but not improved functional recovery. The present study was undertaken to investigate whether the monoclonal L1 antibody 557 that triggers beneficial L1 functions in vitro would trigger these also in femoral nerve repair. We analyzed femoral nerve regeneration in C57BL/6J mice that received this antibody in a hydrogel filled conduit connecting the cut and sutured nerve before its bifurcation, leading to short-term release of antibody by diffusion. Video-based quantitative analysis of motor functions showed improved recovery when compared to mice treated with conduits containing PBS in the hydrogel scaffold, as a vehicle control. This improved recovery was associated with attenuated motoneuron loss, remyelination and improved precision of preferential motor reinnervation. We suggest that function-triggering L1 antibodies applied to the lesion site at the time of injury over a limited time period will not only be beneficial in peripheral, but also central nervous system regeneration. PMID:25393007
Compound nerve conduction velocity – A reflection of proprioceptive afferents?
Antti J. Metso; Kirsi Palmu; Juhani V. Partanen
ObjectiveTo gather the required sample size to compare compound nerve conduction velocities (CV) to cutaneous sensory CVs and motor CVs to find out if there are statistically significant differences between these nerve fibre populations.
Stretch-induced nerve injury: a proposed technique for the study of nerve regeneration and evaluation of the influence of gabapentin on this model
Machado, J.A.; Ghizoni, M.F.; Bertelli, J.; Teske, Gabriel C.; Teske, Guilherme C.; Martins, D.F.; Mazzardo-Martins, L.; Cargnin-Ferreira, E.; Santos, A.R.S.; Piovezan, A.P.
The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP) on nerve regeneration. Male Wistar rats (300 g; n=36) underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001), compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05). Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001), in the density of myelinated fibers/mm2 (P<0.05) and in the degeneration fragments (P<0.01). Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration. PMID:24270909
Parametric transfer function analysis and modeling of blood flow autoregulation in the optic nerve head
Yu, Jintao; Liang, Yi; Thompson, Simon; Cull, Grant; Wang, Lin
The aim of the study was to establish a parametric transfer function to describe the relationship between ocular perfusion pressure (OPP) and blood flow (BF) in the optic nerve head (ONH). A third-order parametric theoretical model was proposed to describe the ONH OPP-BF relationship within the lower OPP range of the autoregulation curve (< 80 mmHg) based on experimentally induced BF response to a rapid intraocular pressure (IOP) increase in 6 rhesus monkeys. The theoretical and actual data fitted well and suggest that this parametric third-order transfer function can effectively describe both the linear and nonlinear feature in dynamic and static autoregulation in the ONH within the OPP range studied. It shows that the BF autoregulation fully functions when the OPP was > 40 mmHg and becomes incomplete when the OPP was < 40 mmHg. This model may be used to help investigating the features of autoregulation in the ONH under different experimental conditions. PMID:24665355
Parametric transfer function analysis and modeling of blood flow autoregulation in the optic nerve head.
Yu, Jintao; Liang, Yi; Thompson, Simon; Cull, Grant; Wang, Lin
The aim of the study was to establish a parametric transfer function to describe the relationship between ocular perfusion pressure (OPP) and blood flow (BF) in the optic nerve head (ONH). A third-order parametric theoretical model was proposed to describe the ONH OPP-BF relationship within the lower OPP range of the autoregulation curve (< 80 mmHg) based on experimentally induced BF response to a rapid intraocular pressure (IOP) increase in 6 rhesus monkeys. The theoretical and actual data fitted well and suggest that this parametric third-order transfer function can effectively describe both the linear and nonlinear feature in dynamic and static autoregulation in the ONH within the OPP range studied. It shows that the BF autoregulation fully functions when the OPP was > 40 mmHg and becomes incomplete when the OPP was < 40 mmHg. This model may be used to help investigating the features of autoregulation in the ONH under different experimental conditions. PMID:24665355
One hour electrical stimulation accelerates functional recovery after femoral nerve repair
Peter Ahlborn; Melitta Schachner; Andrey Irintchev
The clinical outcome of peripheral nerve injuries requiring surgical repair is usually poor and efficient therapies do not exist. Recent work has suggested that low-frequency electrical stimulation of the severed nerve which produces repeated discharges of the parent motoneuron perikarya positively influences axonal regeneration, even if applied once for a period of only 1 h. Here we provide the first evidence
A review of functional neuroimaging studies of vagus nerve stimulation (VNS)
Jeong-Ho Chae; Ziad Nahas; Mikhail Lomarev; Stewart Denslow; Jeffrey P Lorberbaum; Daryl E Bohning; Mark S George
Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many
An experimental study to determine and correlate choline acetyltransferase assay with functional muscle testing after nerve injury.
Vathana, Torpon; Nijhuis, Tim H J; Friedrich, Patricia F; Bishop, Allen T; Shin, Alexander Y
OBJECT Choline acetyltransferase (ChAT) is an enzyme synthesized within the body of a motor neuron whose role is to form the neurotransmitter acetylcholine. Quantification of ChAT levels in motor or mixed nerves has been proposed to provide information regarding the viability of a proximal nerve stump for motor neurotization following brachial plexus injury. To do so requires information regarding normal ChAT levels and those in injured nerves, as well as the correlation of ChAT level determined at surgery with eventual motor recovery. The purpose of this study was to determine ChAT activity in the normal and injured sciatic/peroneal nerve in a rat model, evaluate the correlation between ChAT and motor recovery, find the relationship between ChAT activity and isometric muscle force, and elucidate the parallel between ChAT activity and acetylcholinesterase (AChE) activity. METHODS Sixty animals were divided into 3 groups. The sciatic nerves in Group 1 were transected without repair. Nerves in Group 2 were transected and repaired. Nerves in Group 3 sustained a crush injury followed by transection and reconstruction. All animals were allowed 12 weeks of recovery followed by evaluation of ChAT levels in the peroneal nerve, correlated with measures of maximal isometric tibialis anterior muscle force and muscle weight (the operated side normalized to the control side). Karnovsky AChE staining of peroneal nerve segments was also compared with radiochemical assay of ChAT activity in the same nerve. RESULTS A significant difference in the tibialis anterior isometric tetanic force and the tibialis anterior muscle weight index (TAMI) was noted between Group 1 and Groups 2 and 3 (p < 0.0001); no significant difference was found comparing Group 2 with Group 3. The correlation between the force measurement and the TAMI was 0.382. Both AChE measurement and ChAT activity demonstrated significantly fewer fibers in the operated nerve compared with the contralateral nerve. Intergroup variability could also be illustrated using these tests. The correlation coefficient between the isometric tetanic force measurement and the ChAT analysis in Groups 1 and 2 was 0.468. The correlation for the AChE staining and the isometric tetanic force measurement was 0.111. The correlation between the TAMI and the ChAT levels was 0.773. The correlation between the TAMI and the AChE-stained fibers was 0.640. Correlating AChE staining to the ChAT analysis produced a correlation of 0.712. CONCLUSIONS The great variability in all groups and weak correlations to the functional muscle assessments and the ChAT radiochemical assay made this technique an unreliable method of determining motor nerve viability. PMID:24559224
Changes in sensation after nerve injury or amputation: the role of central factors.
Braune, S; Schady, W
Dynamic changes in somatosensory cortical maps are known to occur in experimental animals subjected to peripheral nerve transection or amputation. To study the sensory effects of central nervous system adaptation to temporary or permanent loss of input from a part of the hand, multimodality quantitative sensory tests were carried out in 11 patients with complete traumatic division and repair of the median or ulnar nerves and in six patients who had undergone amputation of one or more digits. As expected, vibration, two point discrimination, and tactile thresholds were raised in the territory of the injured nerve in a graded fashion, sensitivity being poorest in the patients with the most recent injuries. Surprisingly, localisation was better in the tips than at the base of the hypoaesthetic fingers, suggesting a central attentional gradient. Stimulus-response curves conformed to a power function whose exponent was higher in denervated than in normal skin. Changes in psychophysical functions were also discernible in the intact hand. There was no hyperaesthesia in the territory of the nerve adjacent to the injured one or in the stump in the case of amputees. Central factors contribute to the sensory changes seen after nerve injury, but the functional effects of the cortical reorganisation that follows partial deafferentation are more subtle than a simple heightening of sensitivity in the surrounding skin. PMID:8482960
?2?-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage
Patel, Ryan; Bauer, Claudia S.; Nieto-Rostro, Manuela; Margas, Wojciech; Ferron, Laurent; Chaggar, Kanchan; Crews, Kasumi; Ramirez, Juan D.; Bennett, David L. H.; Schwartz, Arnold; Dickenson, Anthony H.
The ?2?-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and is also the therapeutic target of gabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which ?2?-1 gene expression is disrupted, to determine whether ?2?-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive ?2?-1?/? mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord synaptosomes from ?2?-1?/? mice, and ?2?-1?/? DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, ?2?-1?/? mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of ?2?-2 or ?2?-3 after PSNL in ?2?-1?/? mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL ?2?-1?/? mice. Thus, ?2?-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248
Effect of bleaching whey on sensory and functional properties of 80% whey protein concentrate.
Jervis, S; Campbell, R; Wojciechowski, K L; Foegeding, E A; Drake, M A; Barbano, D M
Whey is a highly functional food that has found widespread use in a variety of food and beverage applications. A large amount of the whey proteins produced in the United States is derived from annatto-colored Cheddar cheese. Color from annatto is undesirable in whey and must be bleached. The objective of this study was to compare 2 commercially approved bleaching agents, benzoyl peroxide (BP) and hydrogen peroxide (HP), and their effects on the flavor and functionality of 80% whey protein concentrate (WPC80). Colored and uncolored liquid wheys were bleached with BP or HP, and then ultrafiltered, diafiltered, and spray-dried; WPC80 from unbleached colored and uncolored Cheddar whey were manufactured as controls. All treatments were manufactured in triplicate. The WPC80 were then assessed by sensory, instrumental, functionality, color, and proximate analysis techniques. The HP-bleached WPC80 were higher in lipid oxidation compounds (specifically hexanal, heptanal, octanal, nonanal, decanal, dimethyl disulfide, and 1-octen-3-one) and had higher fatty and cardboard flavors compared with the other unbleached and BP-bleached WPC80. The WPC80 bleached with BP had lower norbixin concentrations compared with WPC80 bleached with HP. The WPC powders differed in Hunter color values (L, a, b), with bleached powders being more white, less red, and less yellow than unbleached powders. Bleaching with BP under the conditions used in this study resulted in larger reductions in yellowness of the powders made from whey with annatto color than did bleaching with HP. Functionality testing demonstrated that whey bleached with HP treatments had more soluble protein after 10 min of heating at 90°C at pH 4.6 and pH 7 than the no-bleach and BP treatments, regardless of additional color. Overall, HP bleaching caused more lipid oxidation products and subsequent off-flavors compared with BP bleaching. However, heat stability of WPC80 was enhanced by HP bleaching compared with control or BP-bleached WPC80. PMID:22612922
Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients.
Dougherty, Patrick M; Cata, Juan P; Cordella, Joseph V; Burton, Allen; Weng, Han-Rong
Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. More proximal is an area not recognized by the patients as involved with pain or sensory disturbance yet wherein quantitative sensory tests nevertheless reveal altered sensibility. Impairment of perception to light touch, normally conveyed by myelinated fibers, was dramatically altered in all three areas, being approximately 50-fold greater than normal in areas of pain and sensory disturbance as well as in areas of skin perceived by the patients as not affected. Impairment of perception to sharpness, normally conveyed by small myelinated fibers, was most pronounced in areas of on-going pain, intermediate in areas of sensory disturbance and near baseline in more proximal skin of chemotherapy patients. In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers. PMID:15082135
Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells
Bohórquez, Diego V.; Shahid, Rafiq A.; Erdmann, Alan; Kreger, Alex M.; Wang, Yu; Calakos, Nicole; Wang, Fan; Liddle, Rodger A.
Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit's functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems. PMID:25555217
Vagus nerve stimulation improves left ventricular function in a canine model of chronic heart failure
Hamann, Jason J.; Ruble, Stephen B.; Stolen, Craig; Wang, Mengjun; Gupta, Ramesh C.; Rastogi, Sharad; Sabbah, Hani N.
Aims Autonomic dysfunction is a feature of chronic heart failure (HF). This study tested the hypothesis that chronic open-loop electrical vagus nerve stimulation (VNS) improves LV structure and function in canines with chronic HF. Methods and results Twenty-six canines with HF (EF ?35%) produced by intracoronary microembolizations were implanted with a bipolar cuff electrode around the right cervical vagus nerve and connected to an implantable pulse generator. The canines were enrolled in Control (n = 7) vs. VNS therapy (n = 7) or a crossover study, with crossovers occurring at 3 months (C × VNS, n = 6; VNS × C, n = 6). After 6 months of VNS, LVEF and LV end-systolic volume (ESV) were significantly improved compared with Control (?EF Control –4.6 ± 0.9% vs. VNS 6.0 ± 1.6%, P < 0.001) and (?ESV Control 8.3 ± 1.8 mL vs. VNS –3.0 ± 2.3 mL, P = 0.002. Plasma and tissue biomarkers were also improved. In the crossover study, VNS also resulted in a significant improvement in EF and ESV compared with Control (?EF Control –2.3 ± 0.65% vs. VNS 6.7 ± 1.1 mL, P < 0.001 and ?ESV Control 3.2 ± 1.2 mL vs. VNS –4.0 ± 0.9 mL, P < 0.001). Initiation of therapy in the Control group at 3 months resulted in a significant improvement in EF (Control –4.7 ± 1.4% vs. VNS 3.7 ± 0.74%, P < 0.001) and ESV (Control 1.5 ± 1.2 mL vs. NS –5.5 ± 1.6 mL, P = 0.003) by 6 months. Conclusions In canines with HF, long-term, open-looped low levels of VNS therapy improves LV systolic function, prevents progressive LV enlargement, and improves biomarkers of HF when compared with control animals that did not receive therapy. PMID:23883651
Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury
Moss, Andrew; Ingram, Rachel; Koch, Stephanie; Theodorou, Andria; Low, Lucie; Baccei, Mark; Hathway, Gareth J; Costigan, Michael; Salton, Stephen R; Fitzgerald, Maria
Background The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated. Results Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5–50 nmol) to naďve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses. Conclusion VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naďve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain. PMID:19077191
Injectable systems and implantable conduits for peripheral nerve repair.
Lin, Yen-Chih; Marra, Kacey G
Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360,000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid-gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. PMID:22456722
Decreased sensory responses in osteocalcin null mutant mice imply neuropeptide function.
Patterson-Buckendahl, Patricia; Sowinska, Agnieszka; Yee, Stephanie; Patel, Dhara; Pagkalinawan, Stephen; Shahid, Muhammad; Shah, Ankit; Franz, Christopher; Benjamin, Daniel E; Pohorecky, Larissa A
Osteocalcin, the most abundant member of the family of extracellular mineral binding gamma-carboxyglutamic acid proteins is synthesized primarily by osteoblasts. Its affinity for calcium ions is believed to limit bone mineralization. Several of the numerous hormones that regulate synthesis of osteocalcin, including glucocorticoids and parathyroid hormone, are also affected by stressful stimuli that require energy for an appropriate response. Based on our observations of OC responding to stressful sensory stimuli, the expression of OC in mouse and rat sensory ganglia was confirmed. It was thus hypothesized that the behavioral responses of the OC knockout mouse to stressful sensory stimuli would be abnormal. To test this hypothesis, behaviors related to sensory aspects of the stress response were quantified in nine groups of mice, aged 4-14 months, comparing knockout with their wild-type counterparts in six distinctly different behavioral tests. Resulting data indicated the following statistically significant differences: open field grooming frequency following saline injection, wild-type > knockout; paw stimulation with Von Frey fibers, knockout < wild-type; balance beam, knockout mobility < WT; thermal sensitivity to heat (tail flick), knockout < wild-type; and cold, knockout < wild-type. Insignificant differences in hanging wire test indicate that these responses are unrelated to reduced muscle strength. Each of these disparate environmental stimuli provided data indicating alterations of responses in knockout mice that suggest participation of osteocalcin in transmission of information about those sensory stimuli. PMID:22350212
P2X3 and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons
Saloman, Jami L.; Chung, Man-Kyo; Ro, Jin Y.
Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) affect a large percentage of the population. Identifying mechanisms underlying hyperalgesia could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. In this study, we provide evidence of functional interactions between two ligand-gated channels, P2X3 and TRPV1, in trigeminal sensory neurons, and propose that the interactions serve as an underlying mechanism for the development of mechanical hyperalgesia. Mechanical sensitivity of the masseter muscle was assessed in lightly anesthetized rats via an electronic anesthesiometer (Ro et al., 2009). Direct intramuscular injection of a selective P2X3 agonist, ??meATP, induced a dose- and time-dependent hyperalgesia. Mechanical sensitivity in the contralateral muscle was unaffected suggesting local P2X3 mediate the hyperalgesia. Anesthetizing the overlying skin had no effect on ??meATP-induced hyperalgesia confirming the contribution of P2X3 from muscle. Importantly, the ??meATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810. P2X3 was co-expressed with TRPV1 in masseter muscle afferents confirming the possibility for intracellular interactions. Additionally, in a subpopulation of P2X3/TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly amplified following P2X3 activation. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal ganglia cultures. Significant phosphorylation was observed at 15 min, the time point at which behavioral hyperalgesia was prominent. Previously, activation of either P2X3 or TRPV1 had been independently implicated in the development of mechanical hyperalgesia. Our data propose P2X3 and TRPV1 interact in a facilitatory manner, which could contribute to the peripheral sensitization known to underlie masseter hyperalgesia. PMID:23201260
Active compounds and distinctive sensory features provided by American ginseng (Panax quinquefolius L.) extract in a new functional milk beverage.
Tárrega, A; Salvador, A; Meyer, M; Feuillčre, N; Ibarra, A; Roller, M; Terroba, D; Madera, C; Iglesias, J R; Echevarría, J; Fiszman, S
American ginseng (Panax quinquefolius L.) has recognized neurocognitive effects, and a ginsenoside-rich extract of the root of the plant has been shown to improve cognitive functions in young adults. This study aimed at assessing the chemical and sensory profiles of a UHT-treated, low-lactose functional milk containing American ginseng. Individual ginsenosides in the milk were analyzed by HPLC. Descriptive sensory analysis was performed by a trained panel to quantitatively document sensory changes resulting from the addition of ginseng and the UHT process on flavored and unflavored milks. Consumer acceptance of the product was also investigated. Total ginsenoside content in the UHT-treated milk enriched with the ginseng extract after UHT process treatment was 7.52 mg/100 g of milk, corresponding to a recovery of 67.6% compared with the content in the unprocessed extract. The intake of 150 to 300 mL of this ginseng-enriched milk provides the amount of total ginsenosides (11.5 to 23 mg) necessary to improve cognitive function after its consumption. Both the presence of ginsenosides and their thermal treatment affected some sensory properties of the milk, most notably an increase in bitterness and metallic taste, the appearance of a brownish color, and a decrease in milky flavor. Levels of brown color, bitterness, and metallic taste were highest in the industrially processed ginseng-enriched milk. The bitterness attributable to ginseng extract was reduced by addition of vanilla flavor and sucralose. A consumer exploratory study revealed that a niche of consumers exists who are willing to consume this type of product. PMID:22818438
Small Nerve Fiber Pathology in Critical Illness
Latronico, Nicola; Filosto, Massimiliano; Fagoni, Nazzareno; Gheza, Laura; Guarneri, Bruno; Todeschini, Alice; Lombardi, Raffaella; Padovani, Alessandro; Lauria, Giuseppe
Background Degeneration of intraepidermal nerve fibers (IENF) is a hallmark of small fiber neuropathy of different etiology, whose clinical picture is dominated by neuropathic pain. It is unknown if critical illness can affect IENF. Methods We enrolled 14 adult neurocritical care patients with prolonged intensive care unit (ICU) stay and artificial ventilation (? 3 days), and no previous history or risk factors for neuromuscular disease. All patients underwent neurological examination including evaluation of consciousness, sensory functions, muscle strength, nerve conduction study and needle electromyography, autonomic dysfunction using the finger wrinkling test, and skin biopsy for quantification of IENF and sweat gland innervation density during ICU stay and at follow-up visit. Development of infection, sepsis and multiple organ failure was recorded throughout the ICU stay. Results Of the 14 patients recruited, 13 (93%) had infections, sepsis or multiple organ failure. All had severe and non-length dependent loss of IENF. Sweat gland innervation was reduced in all except one patient. Of the 7 patients available for follow-up visit, three complained of diffuse sensory loss and burning pain, and another three showed clinical dysautonomia. Conclusions Small fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in neurocritical care survivors. Its impact on long term disability warrants further studies involving also non-neurologic critical care patients. PMID:24098716
Peripheral nerve tumours: 30-year experience in the surgical treatment.
Gosk, Jerzy; Gutkowska, Olga; Mazurek, Piotr; Koszewicz, Magdalena; Zió?kowski, Piotr
Peripheral nerve tumours are relatively rare type of soft tissue tumours. The aim of this work is to present our experience with surgical treatment of this type of lesions. Clinical material consists of 94 patients (56 females, 38 males), in whom 101 tumours deriving from peripheral nervous system were removed. The patients underwent surgical treatment between 1983 and 2012. Tumours occurred mainly in the upper extremity (72 tumours), less often in the lower extremity (25 tumours). Lesions developed in major peripheral nerves (51 tumours) and small nerve branches (50 tumours). The most common symptoms reported before surgery included presence of tumour mass (100 %), positive Hoffmann-Tinel sign (95.6 %) and paraesthesia (93.4 %). Less often sensory deficit (89.1 %) and pain (71.7 %) were observed. Motor deficit was the least common manifestation (41.3 %). Benign tumours prevailed in presented material (94 tumours). In 7 cases, malignant peripheral nerve sheath tumour (MPNST) was identified. As a result of surgical treatment in the group of tumours deriving from major peripheral nerves, in 87.8 % of the patients, pain relief was achieved; in 84 %, Hoffmann-Tinel sign was negative; and in 79 %, paraesthesia resolved. Sensory function improvement was observed in 51.2 % of the patients while motor function improved in 26.3 % of the patients. None of the patients experienced tumour relapse. In the group of tumours deriving from small nerve branches, 47 patients had no signs of tumour recurrence. One female patient diagnosed with MPNST suffered a relapse. Obtaining satisfactory results of peripheral nerve tumour treatment requires both careful differential diagnosis and well thought-out strategy at every stage of therapeutic management. PMID:25727458
Functional and Neuroanatomical Effects of Vaginal Distention and Pudendal Nerve Crush in the Female Rat
PurposeWe tested the hypothesis that neuroanatomical degeneration near the external urethral sphincter (EUS) would parallel urinary dysfunction after vaginal distention or bilateral pudendal nerve crush in female rats.
Nerve fiber planimetry in acute and chronic nerve lesions and in nerve lesions in continuity.
Guelinckx, P J; Boeckx, W D; Dom, R; Gruwez, J A
The level of resection of damaged nerve tissue in acute and chronic nerve lesions was determined on the basis of the vascular structure, the consistency of the nerve during palpation, the amount of interfascicular connective tissue, and the mushroom formation of the fascicles. Intraoperative electrophysiologic recordings were performed on the cut nerve ends to determine the function of the axons. Postoperative planimetric analyses of cross sections made through the resected nerve stumps were performed to measure axonal and endoneural tube diameters and to correlate these results with the clinical criteria used through the operating microscope. Axons in the proximal nerve ends of acute and chronic nerve lesions displayed a similar mean diameter. Endoneural tubes in chronic nerve lesions shrunk significantly as nerve repair was delayed. In several nerve lesions in continuity, axons remained present across the injured site despite absence of electrical conduction. When comparing the results of axonal or endoneural tube diameters of chronic nerve lesions to the results of other studies or acute nerve lesions, we demonstrated that careful examination through the operating microscope provided valid information about the proper management and resection level of chronic nerve lesions. Electrophysiologic evaluation aided the surgical management but was not useful for the resection of the distal damaged nerve segment. The presence of an evoked potential in the proximal nerve ends guaranteed a nearly normal nerve fiber diameter distribution, while the absence of such a potential in the distal nerve ends indicated an abnormal, absent, or disturbed endoneural tube diameter histogram. PMID:4034768
Cardiac autonomic involvement and peripheral nerve function in patients with diabetic neuropathy.
Spitzer, A; Lang, E; Birklein, F; Claus, D; Neundörfer, B
The aim of our study was to investigate the relationship between cardiac autonomic neuropathy and dysfunction of myelinated and unmyelinated nerve fibres in the peripheral nerve. We measured nerve conduction velocities, warmth/cold perception thresholds at the foot dorsum, sympathetic skin response (SSR), and performed the quantitative sudomotor axon reflex test (QSART). Forty-three diabetic patients with distal-symmetric polyneuropathy were included. According to the results of heart rate variation, 20 patients had cardiac autonomic neuropathy (CAN+). Apart from motor nerve conduction velocities, all tests were more often abnormal in CAN+ patients. Warmth thresholds (afferent C-fibres) and reduced compound muscle action potentials (CMAPs) of the tibial and peroneal nerve, indicating axonal damage, were more often abnormal in CAN+. Cold threshold and sural nerve conduction velocity were indicators of involvement of myelinated small and large nerve fibres, but not of the cardiac autonomic system. Ninety-four percent (94%) of patients with absent SSR and 78% of patients with abnormal QSART had CAN+. SSR and QSART may be useful for assessment of autonomic neuropathy in diabetic patients with cardiac arrhythmia where direct measurement of heart rate variability is not possible. In the majority of our patients with CAN+, the vagal-cardiac and the sudomotor-sympathetic systems were involved simultaneously, although two entirely different systems were tested. This may reflect a C-fibre directed selectivity of the pathological process in autonomic diabetic neuropathy. In conclusion our results show that diabetics with and without cardiac autonomic neuropathy have a different profile of involvement of peripheral nerve fibres. PMID:9218965
Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.
Elzinga, Kate; Tyreman, Neil; Ladak, Adil; Savaryn, Bohdan; Olson, Jaret; Gordon, Tessa
Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons were chronically axotomized and/or tibial (TIB) SCs and ankle extensor muscles were chronically denervated by transection and ligation in rats. The CP and TIB nerves were cross-sutured after three months and subjected to either sham or one hour 20Hz ES. Using retrograde tracing, we found that ES significantly increased the numbers of both motor and sensory neurons that regenerated their axons after a three month period of chronic CP axotomy and/or chronic TIB SC denervation. Muscle and motor unit forces recorded to determine the numbers of neurons that reinnervated gastrocnemius muscle demonstrated that ES significantly increased the numbers of motoneurons that reinnervated chronically denervated muscles. We conclude that electrical stimulation of chronically axotomized motor and sensory neurons is effective in accelerating axon outgrowth into chronically denervated nerve stumps and improving target reinnervation after delayed nerve repair. Possible mechanisms for the efficacy of ES in promoting axon regeneration and target reinnervation after delayed nerve repair include the upregulation of neurotrophic factors. PMID:25842267
The value of skin biopsy with recording of intraepidermal nerve fiber density and quantitative sensory testing in the assessment of small fiber involvement in patients with different causes of polyneuropathy.
Nebuchennykh, Maria; Lřseth, Sissel; Lindal, Sigurd; Mellgren, Svein Ivar
The primary aim of our study was to demonstrate how the diagnostic characteristics of skin biopsy used to evaluate small fiber involvement in patients with different causes of polyneuropathy are intrinsically related to the method used to establish the reference values (cut-off values). We also investigated intraepidermal nerve fiber (IENF) density and abnormalities in quantitative sensory testing (QST) in patients with different causes of polyneuropathy and signs of small fiber involvement. A total of 210 patients with symptoms and signs of polyneuropathy were entered into the study. All patients underwent neurological examination, nerve conduction studies, QST on the thigh and distal part of the calf with detection of warm and cold perception thresholds, and skin biopsy with assessment of IENF density. Cut-off values for IENF density were established from our reference material using Z-scores (calculated from multiple regression analysis), fifth percentile, and receiver operating characteristic (ROC) analysis. Of the patients participating in the study, 65 had an established diagnosis of diabetes mellitus, 70 were classified with idiopathic polyneuropathy, and 75 had other possible causes of polyneuropathy. Forty-five patients met the criteria for small fiber polyneuropathy (SFN), and the remaining 165 had also involvement of large nerve fibers. Of the total patient cohort, 84 (40%) had reduced IENF density based on the Z-score, and 106 patients (50%) had at least one abnormality based on QST. In the SFN group, skin biopsy showed a sensitivity of 31% and a specificity of 98% when reference values were presented with Z-scores. When the fifth percentile was used as the cut-off value (6.7 fibers/mm), sensitivity was 35% and specificity 95%. Applying the ROC analysis with a chosen sensitivity of 78% and specificity of 64%, we had a cut-off point of 10.3 fibers/mm. We conclude that skin biopsy with assessment of IENF is a useful method for investigating patients with SFN. The diagnostic value of the test, however, depends upon on the approach used to estimate the reference values. PMID:19252773
Electrical Stimulation to Conductive Scaffold Promotes Axonal Regeneration and Remyelination in a Rat Model of Large Nerve Defect
Zhang, Yongguang; Liang, Wei; Wu, Siyu; Luo, Zhuojing
Background Electrical stimulation (ES) has been shown to promote nerve regeneration when it was applied to the proximal nerve stump. However, the possible beneficial effect of establishing a local electrical environment between a large nerve defect on nerve regeneration has not been reported in previous studies. The present study attempted to establish a local electrical environment between a large nerve defect, and examined its effect on nerve regeneration and functional recovery. Methodology/Findings In the present study, a conductive scaffold was constructed and used to bridge a 15 mm sciatic nerve defect in rats, and intermittent ES (3 V, 20 Hz) was applied to the conductive scaffold to establish an electrical environment at the site of nerve defect. Nerve regeneration and functional recovery were examined after nerve injury repair and ES. We found that axonal regeneration and remyelination of the regenerated axons were significantly enhanced by ES which was applied to conductive scaffold. In addition, both motor and sensory functional recovery was significantly improved and muscle atrophy was partially reversed by ES localized at the conductive scaffold. Further investigations showed that the expression of S-100, BDNF (brain-derived neurotrophic factor), P0 and Par-3 was significantly up-regulated by ES at the conductive scaffold. Conclusions/Significance Establishing an electrical environment with ES localized at the conductive scaffold is capable of accelerating nerve regeneration and promoting functional recovery in a 15 mm nerve defect in rats. The findings provide new directions for exploring regenerative approaches to achieve better functional recovery in the treatment of large nerve defect. PMID:22737243
Methods to measure damage to sensory systems following toxicant exposure vary from rapid and subjective tests (e.g., pinna reflex) to time-consuming and objective tests (e.g., psychophysical tests). eflex modification of the startle response represents an alternative technique in...
Abstract. Sensory experience alters the functional orga-nization of cortical networks. Previous studies using
Kilgard, Michael P.
the representation of the sensory environment. Different combinations of receptive-field, temporal, and spectro modulated tones altered the maximum cortical following rate. Exposure to complex acoustic sequences led cortex (A1). For the purpose of this review, acoustic experience can be simply thought of as the spatial
Vagal Nerve Stimulation Reverses Aberrant Dopamine System Function in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia
Perez, Stephanie M.; Carreno, Flavia R.; Frazer, Alan
Vagal nerve stimulation (VNS) is an alternative therapy for epilepsy and treatment refractory depression. Here we examine VNS as a potential therapy for the treatment of schizophrenia in the methylozoxymethanol acetate (MAM) rodent model of the disease. We have previously demonstrated that hyperactivity within ventral regions of the hippocampus (vHipp) drives the dopamine system dysregulation in this model. Moreover, by targeting the vHipp directly, we can reverse aberrant dopamine system function and associated behaviors in the MAM model. Although the central effects of VNS have not been completely delineated, positron emission topographic measurements of cerebral blood flow in humans have consistently reported that VNS stimulation induces bilateral decreases in hippocampal activity. Based on our previous observations, we performed in vivo extracellular electrophysiological recordings in MAM- and saline-treated rats to evaluate the effect of chronic (2 week) VNS treatment on the activity of putative vHipp pyramidal neurons, as well as downstream dopamine neuron activity in the ventral tegmental area. Here we demonstrate that chronic VNS was able to reverse both vHipp hyperactivity and aberrant mesolimbic dopamine neuron function in the MAM model of schizophrenia. Additionally, VNS reversed a behavioral correlate of the positive symptoms of schizophrenia. Because current therapies for schizophrenia are far from adequate, with a large number of patients discontinuing treatment due to low efficacy or intolerable side effects, it is important to explore alternative nonpharmacological treatments. These data provide the first preclinical evidence that VNS may be a possible alternative therapeutic approach for the treatment of schizophrenia. PMID:25009259
Manual stimulation of forearm muscles does not improve recovery of motor function after injury to a mixed peripheral nerve
N. Sinis; O. Guntinas-Lichius; A. Irintchev; E. Skouras; S. Kuerten; S. P. Pavlov; H. E. Schaller; S. A. Dunlop; D. N. Angelov
Transection and re-anastomosis of the purely motor facial nerve leads to poor functional recovery. However, we have recently\\u000a shown in rat that manual stimulation (MS) of denervated vibrissal muscles reduces the number of polyinnervated motor endplates\\u000a and promotes full recovery of whisking. Here, we examined whether MS of denervated rat forearm muscles would also improve\\u000a recovery following transection and suture
Diagnostic ability of a linear discriminant function for optic nerve head parameters measured with optical coherence tomography for perimetric glaucoma
L E Pablo; A Ferreras; A B Pajarín; P Fogagnolo
Background\\/aimsTo calculate and validate a linear discriminant function (LDF) for optical coherence tomography (OCT) to improve the diagnostic ability of isolated optic nerve head (ONH) parameters to discriminate between healthy individuals and glaucoma patients.MethodsTwo independent samples (teaching and validating sets) were prospectively selected. The teaching set (54 normal eyes and 73 glaucoma patients) was used to calculate the LDF. The
Astrocytes in sensory circumventricular organs of the rat brain express functional binding sites for endothelin.
Gebke, E; Müller, A R; Pehl, U; Gerstberger, R
Sensory circumventricular organs bordering the anterior third cerebral ventricle, the subfornical organ and the organum vasculosum laminae terminalis, lack blood-brain barrier characteristics and are therefore accessible to circulating peptides like endothelins. Astrocytes of the rat subfornical organ and organum vasculosum laminae terminalis additionally showed immunocytochemical localization of endothelin-1/endothelin-3-like peptides, possibly acting as circumventricular organ-intrinsic modulators. Employing [125I]endothelin-1 as radioligand, quantitative autoradiography demonstrated specific binding sites throughout the rat organum vasculosum laminae terminalis and subfornical organ, and competitive displacement studies revealed expression of both ET(A) and ET(B) receptor subtypes for either circumventricular organ. ET(B) receptor binding prevailed for the whole brain and ET(A) receptors could be labelled in the peripheral vascular system. To characterize endothelin-specific receptors in astrocytes of both circumventricular organs, alterations in the intracellular calcium concentration due to endothelin-1/endothelin-3 stimulation were studied in primary culture of subfornical organ and organum vasculosum laminae terminalis cells obtained from early postnatal rat pups. Endothelin-1 and endothelin-3 induced Ca(2+) transients in 9-13% of either subfornical organ or organum vasculosum laminae terminalis astrocytes, respectively, and some glial cells (subfornical organ: 2%, organum vasculosum laminae terminalis: 5%) responded to both endothelin analogues. The antagonistic action of BQ123 specific for ET(A) receptors (74% of all astrocytes tested), and the pronounced responsiveness to the ET(B) receptor agonist [4Ala]ET-1 (subfornical organ: 27%, organum vasculosum laminae terminalis: 35%) demonstrated glial expression of both endothelin receptor subtypes. Agonist-induced elevations in the intracellular calcium concentration proved to be independent of extracellular Ca(2+). In summary, the results indicate that endothelin(s) interact(s) with circumventricular organ astrocytes. Competitive receptor binding techniques using brain tissue sections as well as a fura-2 loaded primary cell culture system of the subfornical organ and organum vasculosum laminae terminalis demonstrate glial expression of functional ET(A) and ET(B) receptors, with calcium as intracellular messenger emerging primarily from intracellular stores. Endothelin(s) of both circulating and circumventricular organ-intrinsic origin may afferently transfer information important for cardiovascular homeostasis to circumventricular organs serving as "windows to the brain". PMID:10799769
Clinical disease severity and axonal dysfunction in hereditary motor and sensory neuropathy Ia
Camiel Verhamme; Ivo N. van Schaik; Johannes H. T. M. Koelman; Rob J. de Haan; Marinus Vermeulen; Marianne de Visser
Background Hereditary motor and sensory neuropathy type Ia (HMSN Ia) is known as a primarily demyelinating peripheral nerve disease. Evidence is accumulating that axonal involvement determines the course of the disease process. Methods Fifty-one patients were investigated. Physical disability and impairments were scored. Nerve conduction velocities (NCVs) were used as indirect measures for myelination status and compound muscle\\/sensory nerve action
Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees
NASA Astrophysics Data System (ADS)
Tan, Daniel W.; Schiefer, Matthew A.; Keith, Michael W.; Anderson, J. Robert; Tyler, Dustin J.
Objective. Stability and selectivity are important when restoring long-term, functional sensory feedback in individuals with limb-loss. Our objective is to demonstrate a chronic, clinical neural stimulation system for providing selective sensory response in two upper-limb amputees. Approach. Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of the upper-limb. Main results. Nerve stimulation produced a selective sensory response on 19 of 20 contacts and 16 of 16 contacts in subjects 1 and 2, respectively. Stimulation elicited multiple, distinct percept areas on the phantom and residual limb. Consistent threshold, impedance, and percept areas have demonstrated that the neural interface is stable for the duration of this on-going, chronic study. Significance. We have achieved selective nerve response from multi-contact cuff electrodes by demonstrating characteristic percept areas and thresholds for each contact. Selective sensory response remains consistent in two upper-limb amputees for 1 and 2 years, the longest multi-contact sensory feedback system to date. Our approach demonstrates selectivity and stability can be achieved through an extraneural interface, which can provide sensory feedback to amputees.
Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering
NASA Astrophysics Data System (ADS)
Neal, Rebekah Anne
Peripheral nerve transection occurs commonly in traumatic injury, causing motor and sensory deficits distal to the site of injury. One option for surgical repair is the nerve conduit. Conduits currently on the market are hollow tubes into which the nerve ends are sutured. Although these conduits fill the gap, they often fail due to the slow rate of regeneration over long gaps. To facilitate increased speed of regeneration and greater potential for functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in peripheral nerve regeneration. In this dissertation, I fabricated laminin-1 and laminin-polycaprolactone (PCL) blend nanofibers that mimic the geometry and functionality of the peripheral nerve basement membrane. These fibers resist hydration in aqueous media and require no harsh chemical crosslinkers. Adhesion and differentiation of both neuron-like and neuroprogenitor cells is improved on laminin nanofibrous meshes over two-dimensional laminin substrates. Blend meshes with varying laminin content were characterized for composition, tensile properties, degradation rates, and bioactivity in terms of cell attachment and axonal elongation. I have established that 10% (wt) laminin content is sufficient to retain the significant neurite-promoting effects of laminin critical in peripheral nerve repair. In addition, I utilized modified collector plate design to manipulate electric field gradients during electrospinning for the fabrication of aligned nanofibers. These aligned substrates provide enhanced directional guidance cues to the regenerating axons. Finally, I replicated the clinical problem of peripheral nerve transection using a rat tibial nerve defect model for conduit implantation. When the lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment, I observed significant recovery of sensory and motor function over six weeks. This recovery was supported by nerve conduction studies and electromyography which described impulse transmission, muscle stimulation, and foot twitch through the region of regeneration. These studies provide a firm foundation for the use of natural-synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. The similarity in surgical technique and obvious benefit to the patient should lead to rapid translation into clinical application.
[Sensory sensitization, part II: Pathophysiology in dysfunctional disorders. Understanding the inner life of the nerve pathways may explain hitherto unexplainable symptoms].
Levander, Hans
This article is based on a vast clinical experience from patients presenting with widespread pain syndromes as well as dysfunctional symptoms from inner organs. A literature survey has been performed. Allodynia and hyperalgesia that partly explain the fibromyalgia and local myalgia syndromes seem to arise from a pathophysiological process of nociceptive sensitisation. It is proposed that the concept of "sensory sensitisation dysfunctional disorders" be applied to conditions like bronchial hyperreactivity, Da Costas syndrome, Dercum's disease (Adipositas dolorosa), dry eyes and mouth syndrome, fibromyalgia, gastralgia, globus hystericus, interstitial cystitis, chronic prostatitis, irritable bowel syndrome, photo- and phonosensitivity, rhinitis, tension headache, tinnitus, vestibulitis syndrome. These dysfunctional disorders cannot be satisfactorily explained by presently known pathophysiological models like ongoing inflammatory process, tissue degeneration, fibrosis, blood vessel diseases, tumours, immune reactions, toxic or deficiency conditions, metabolic disturbances. Neurogenic mechanisms also seem to play an important role in the pathophysiology of arthritic conditions, and might be worthwhile to include in forthcoming discussions concerning the aetiology of chronic inflammatory disease. PMID:12789809
Nerve Regeneration After Radiofrequency Application
Nobuyasu Ochiai; James P. Tasto; Seiji Ohtori; Norimasa Takahashi; Hideshige Moriya; David Amiel
Background: Many patients with chronic tendinosis have experienced early pain relief after application of bipolar radiofrequency treatment. It is hypothesized that the mechanism of action may be the acute degeneration and\\/or ablation of sensory nerve fibers.Hypothesis: After ablation or degeneration by bipolar radiofrequency, nerve fibers will have the ability to regenerate with time.Study Design: Controlled laboratory study.Methods: Eighteen Sprague-Dawley rats
Use of axonal projection patterns for the homologisation of cerebral nerves in Opisthobranchia, Mollusca and Gastropoda
Introduction Gastropoda are guided by several sensory organs in the head region, referred to as cephalic sensory organs (CSOs). These CSOs are innervated by distinct nerves. This study proposes a unified terminology for the cerebral nerves and the categories of CSOs and then investigates the neuroanatomy and cellular innervation patterns of these cerebral nerves, in order to homologise them. The homologisation of the cerebral nerves in conjunction with other data, e.g. ontogenetic development or functional morphology, may then provide insights into the homology of the CSOs themselves. Results Nickel-lysine axonal tracing ("backfilling") was used to stain the somata projecting into specific nerves in representatives of opisthobranch Gastropoda. Tracing patterns revealed the occurrence, size and relative position of somata and their axons and enabled these somata to be mapped to specific cell clusters. Assignment of cells to clusters followed a conservative approach based primarily on relative location of the cells. Each of the four investigated cerebral nerves could be uniquely identified due to a characteristic set of soma clusters projecting into the respective nerves via their axonal pathways. Conclusions As the described tracing patterns are highly conserved morphological characters, they can be used to homologise nerves within the investigated group of gastropods. The combination of adequate number of replicates and a comparative approach allows us to provide preliminary hypotheses on homologies for the cerebral nerves. Based on the hypotheses regarding cerebral nerve homology together with further data on ultrastructure and immunohistochemistry of CSOs published elsewhere, we can propose preliminary hypotheses regarding homology for the CSOs of the Opisthobranchia themselves. PMID:23597272
Chorda Tympani Nerve Terminal Field Maturation and Maintenance Is Severely Altered Following Changes To Gustatory Nerve Input to the Nucleus of the Solitary Tract
Dudgeon, Sara L.; Hill, David L.
Neural competition among multiple inputs can affect the refinement and maintenance of terminal fields in sensory systems. In the rat gustatory system, the chorda tympani, greater superficial petrosal, and glossopharyngeal nerves have distinct but overlapping terminal fields in the first central relay, the nucleus of the solitary tract (NTS). This overlap is largest at early postnatal ages followed by a significant refinement and pruning of the fields over a three-week period, suggesting that competitive mechanisms underlie the pruning. Here, we manipulated the putative competitive interactions among the three nerves by sectioning the greater superficial petrosal and glossopharyngeal nerves at postnatal day 15 (P15), P25, or at adulthood, while leaving the chorda tympani nerve intact. The terminal field of the chorda tympani nerve was assessed 35 days following nerve sections, a period before the sectioned nerves functionally regenerated. Regardless of the age when the nerves were cut, the chorda tympani nerve terminal field expanded to a volume four times larger than sham controls. Terminal field density measurements revealed that the expanded terminal field was similar to P15 control rats. Thus, it appears that the chorda tympani nerve terminal field defaults to its early postnatal field size and shape when the nerves with overlapping fields are cut, and this anatomical plasticity is retained into adulthood. These findings not only demonstrate the dramatic and lifelong plasticity in the central gustatory system, but also suggest that corresponding changes in functional and taste-related behaviors will accompany injury-induced changes in brainstem circuits. PMID:21613473
The Endocranial Anatomy of Therizinosauria and Its Implications for Sensory and Cognitive Function
Lautenschlager, Stephan; Rayfield, Emily J.; Altangerel, Perle; Zanno, Lindsay E.; Witmer, Lawrence M.
Background Therizinosauria is one of the most enigmatic and peculiar clades among theropod dinosaurs, exhibiting an unusual suite of characters, such as lanceolate teeth, a rostral rhamphotheca, long manual claws, and a wide, opisthopubic pelvis. This specialized anatomy has been associated with a shift in dietary preferences and an adaptation to herbivory. Despite a large number of discoveries in recent years, the fossil record for Therizinosauria is still relatively poor, and cranial remains are particularly rare. Methodology/Principal Findings Based on computed tomographic (CT) scanning of the nearly complete and articulated skull of Erlikosaurus andrewsi, as well as partial braincases of two other therizinosaurian taxa, the endocranial anatomy is reconstructed and described. The wider phylogenetic range of the described specimens permits the evaluation of sensory and cognitive capabilities of Therizinosauria in an evolutionary context. The endocranial anatomy reveals a mosaic of plesiomorphic and derived characters in therizinosaurians. The anatomy of the olfactory apparatus and the endosseous labyrinth suggests that olfaction, hearing, and equilibrium were well-developed in therizinosaurians and might have affected or benefited from an enlarged telencephalon. Conclusion/Significance This study presents the first appraisal of the evolution of endocranial anatomy and sensory adaptations in Therizinosauria. Despite their phylogenetically basal position among maniraptoran dinosaurs, therizinosaurians had developed the neural pathways for a well developed sensory repertoire. In particular olfaction and hearing may have played an important role in foraging, predator evasion, and/or social complexity. PMID:23284972
Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors
Grosmaitre, Xavier; Santarelli, Lindsey C; Tan, Jie; Luo, Minmin; Ma, Minghong
Most sensory systems are primarily specialized to detect one sensory modality. Here we report that olfactory sensory neurons (OSNs) in the mammalian nose can detect two distinct modalities transmitted by chemical and mechanical stimuli. As revealed by patch-clamp recordings, many OSNs respond not only to odorants, but also to mechanical stimuli delivered by pressure ejections of odor-free Ringer solution. The mechanical responses correlate directly with the pressure intensity and show several properties similar to those induced by odorants, including onset latency, reversal potential and adaptation to repeated stimulation. Blocking adenylyl cyclase or knocking out the cyclic nucleotide–gated channel CNGA2 eliminates the odorant and the mechanical responses, suggesting that both are mediated by a shared cAMP cascade. We further show that this mechanosensitivity enhances the firing frequency of individual neurons when they are weakly stimulated by odorants and most likely drives the rhythmic activity (theta oscillation) in the olfactory bulb to synchronize with respiration. PMID:17310245
Influence of human skin injury on regeneration of sensory neurons
O. Taherzadeh; W. R. Otto; U. Anand; J. Nanchahal; P. Anand
The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration
Delayed decrement of the nerve impulse propagation during induced limb ischaemia in chronic hepatic failure
V K Nielsen; T Kardel
Sensory thresholds for vibrations and electrical shocks and the sensory nerve conduction velocity (median nerve) were measured during 30 minutes of induced limb ischaemia in 10 normal subjects and 15 patients with chronic hepatic failure. Sensory action potentials were recorded simultaneously at the wrist and elbow. Seven patients (group A) had a normal perception time for vibrations. As in normal
Elizabeth Keating; R. Neill Hadder
Anthropological studies of sensory impairment address biological conditions and cultural disablement while contributing to theoretical discussions of cultural competence, communicative practices, the role of narrative, and features of identity, ideologies, and technology. As boundary cases, impairments can disclose essential aspects of the senses in human life. Sensory impairment studies navigate the complexities of comparing dominant sensory discourses with individual sense
Elizabeth Keating; R. Neill Hadder
Anthropological studies of sensory impairment address biological conditions and cultural disablement while contributing to theoretical discussions of cultural competence, communicative practices, the role of narrative, and features of identity, ideologies, and technology. As boundary cases, impairments can disclose essential aspects of the senses in human life. Sensory impairment studies navigate the complexities of comparing dominant sensory discourses with individual sense
The utility of clinical neurophysiological and quantitative sensory testing for trigeminal neuropathy.
Jääskeläinen, Satu K
This article reviews the utility of neurophysiological recordings and quantitative sensory testing (QST) in providing sensitive, quantitative, and objective tests for the diagnosis and localization of damage to the trigeminal nerve. Electromyography and recordings of the masseter reflex and compound muscle action potential evoked by transcranial magnetic stimulation or direct electrical stimulation of the masseteric nerve can be of value in evaluating the function of a motor neurons supplying the muscles of mastication. Orthodromic recording of the sensory action potential and trigeminal somatosensory-evoked potential recording with the near-nerve stimulation technique are sensitive tools for the investigation of trigeminal sensory Abeta afferents, whereas recordings of polysynaptic trigeminal brainstem reflexes and tactile QST are less sensitive. At late stages of recovery, the blink reflex and masseter inhibitory reflex are often normal, but at earlier stages, the blink reflex recording has good prognostic value, and the presence of a reflex response may confirm continuity of the nerve trunk after partial laceration. Trigeminal small-fiber function (Adelta and C) can be studied with thermal QST of the cool, warm, heat pain, and cold pain detection thresholds or with laser-evoked potential recording. Thermal QST may remain abnormal years after axonal damage and aids in the diagnosis of late sequelae of trigeminal nerve injury. In a study of the diagnostic value of neurography, blink reflex and thermal QST, and various commonly used clinical sensory tests, neurophysiologic tests and thermal QST had better sensitivity (50% to 88% vs 40% to 59%) and negative predictive values (78% to 100% vs 70% to 74%) compared to clinical examination, whereas the specificity (55% to 100%) and positive predictive values (48% to 73%) were similar. At 1 year after trigeminal nerve injury, the risk of a false negative finding with clinical sensory testing was 94%, whereas the combination of nerve conduction recordings and thermal QST increased the diagnostic yield to 100% in patients with long-standing postsurgical sensory alteration. In conclusion, clinical neurophysiological recordings and QST improve the diagnostic accuracy for trigeminal neuropathy. PMID:15636020
Depressed Adrenergic Nerve Function in Tibial Arteries of Two-Kidney One Clip Goldblatt Hypertensive Dogs
Ben G. Zimmerman; Patricia L. Friedman; Pancras C. Wong
Tibial arteries removed from normotensive dogs and from two-kidney one clip Goldblatt hypertensive dogs, 6–34 days after renal artery constriction, were studied in vitro. Contractions were elicited by transmural stimulation and norepinephrine added to the organ bath. Arteries from the hypertensive dogs exhibited depressed responsiveness to adrenergic nerve stimulation, but not to the lower concentrations of norepinephrine. However, the maximal
Cranial sensory ganglia neurons require intrinsic N-cadherin function for guidance of afferent fibers to their final targets
LaMora, Angela; Voigt, Mark M.
Cell adhesion molecules, such as N-cadherin (cdh2), are essential for normal neuronal development, and as such have been implicated in an array of processes including neuronal differentiation and migration, and axon growth and fasciculation. Cdh2 is expressed in neurons of the peripheral nervous system during development, but its role in these cells during this time is poorly understood. Using the transgenic zebrafish line, tg(p2xr3.2:eGFPsl1), we have examined the involvement of cdh2 in the formation of sensory circuits by the peripheral nervous system. The tg(p2xr3.2:eGFPsl1) fish allows visualization of neurons comprising gV, gVII, gIX and gX and their axons throughout development. Reduction of cdh2 in this line was achieved by either crosses to the cdh2-mutant strain, glass onion (glo) or injection of a cdh2 morpholino (MO) into single-cell embryos. Here we show that cdh2 function is required to alter the directional vectors of growing axons upon reaching intermediate targets. The central axons enter the hindbrain appropriately but fail to turn caudally towards their final targets. Similarly, the peripheral axons extend ventrally, but fail to turn and project along a rostral/caudal axis. Furthermore, by expressing dominant negative cdh2 constructs selectively within cranial sensory ganglia (CSG) neurons, we found that cdh2 function is necessary within the axons to elicit these stereotypic turns, thus demonstrating that cdh2 acts cell autonomously. Together, our in vivo data reveal a novel role for cdh2 in the establishment of circuits by peripheral sensory neurons. PMID:19356698
Parallel Changes in Structural and Functional Measures of Optic Nerve Myelination after Optic Neuritis
van der Walt, Anneke; Kolbe, Scott; Mitchell, Peter; Wang, Yejun; Butzkueven, Helmut; Egan, Gary; Yiannikas, Con; Graham, Stuart; Kilpatrick, Trevor; Klistorner, Alexander
Introduction Visual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON. Methods Thirty acute ON patients were studied at 1,3,6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had recovered sufficiently for latency to be measured in 23 (76.7%) patients with seven patients having no recordable mfVEP in more than 66% of segments in at least one test. Only data from these 23 patients was analysed further. Results Both latency and lesion length showed significant recovery during the follow-up period. Lesion length and mfVEP latency were highly correlated at 1 (r = 0.94, p = <0.0001) and 12 months (r = 0.75, p < 0.001). Both measures demonstrated a similar trend of recovery. Speed of latency recovery was faster in the early follow-up period while lesion length shortening remained relatively constant. At 1 month, latency delay was worse by 1.76ms for additional 1mm of lesion length while at 12 months, 1mm of lesion length accounted for 1.94ms of latency delay. Conclusion A strong association between two putative measures of demyelination in early and chronic ON was found. Parallel recovery of both measures could reflect optic nerve remyelination. PMID:26020925
Hyperalgesic actions of cytokines on peripheral nerves
Robert R. Myers; Rochelle Wagner; Linda S. Sorkin
\\u000a The relationship between nerve injury and pain is pervasive in medicine, being both a simple, common experience and an important\\u000a diagnostic tool. Acute trauma to a nerve is almost always painful and has been experienced by many people in association with\\u000a sports and workplace activities. In these cases, injuries occur usually because of nerve stretching or compression, damaging\\u000a sensory axons
Functional Brain Imaging of Multi-sensory Vestibular Processing during Computerized Dynamic Posturography using Near-Infrared Spectroscopy
Karim, Helmet; Fuhrman, Susan I; Sparto, Patrick; Furman, Joseph; Huppert, Theodore
Functional near-infrared spectroscopy (fNIRS) is a non-invasive brain imaging method that uses light to record regional changes in cerebral blood flow in the cortex during activation. FNIRS uses portable wearable sensors to allow measurements of brain activation during tasking. In this study, fNIRS was used to investigate how the brain processes information from multiple sensory modalities during dynamic posturography. Fifteen healthy volunteers (9M/6F; ages 28 +/? 9 yrs) participated in the posturography study while undergoing fNIRS brain imaging. Four standard conditions from the sensory organization test (SOT) were performed and a bilateral fNIRS probe was used to examine the cortical brain responses from the frontal, temporal, and parietal brain regions. We found there was bilateral activation in the temporal-parietal areas (superior temporal gyrus, STG, and supramarginal gyrus, SMG) when both vision and proprioceptive information was degraded; forcing reliance on primarily vestibular information in the control of balance. This is consistent with previous reports of the role of these regions in vestibular control and demonstrates the potential utility of fNIRS in the study of cortical control of vestibular function during standing balance tasks. PMID:23419940
Entrapment of the superficial peroneal nerve: an anatomical insight.
Tzika, Maria; Paraskevas, George; Natsis, Konstantinos
Entrapment of the superficial peroneal nerve is an uncommon neuropathy that may occur because of mechanical compression of the nerve, usually at its exit from the crural fascia. The symptoms include sensory alterations over the distribution area of the superficial peroneal nerve. Clinical examination, electrophysiologic findings, and imaging techniques can establish the diagnosis. Variations in the superficial peroneal sensory innervation over the dorsum of the foot may lead to variable results during neurologic examination and variable symptomatology in patients with nerve entrapment or lesions. Knowledge of the nerve's anatomy at the lower leg, foot, and ankle is of essential significance for the neurologist and surgeon intervening in the area. PMID:25815655
Selective Tracing of Auditory Fibers in the Avian Embryonic Vestibulocochlear Nerve
Allen-Sharpley, Michelle R.; Tjia, Michelle; Cramer, Karina S.
The embryonic chick is a widely used model for the study of peripheral and central ganglion cell projections. In the auditory system, selective labeling of auditory axons within the VIIIth cranial nerve would enhance the study of central auditory circuit development. This approach is challenging because multiple sensory organs of the inner ear contribute to the VIIIth nerve 1. Moreover, markers that reliably distinguish auditory versus vestibular groups of axons within the avian VIIIth nerve have yet to be identified. Auditory and vestibular pathways cannot be distinguished functionally in early embryos, as sensory-evoked responses are not present before the circuits are formed. Centrally projecting VIIIth nerve axons have been traced in some studies, but auditory axon labeling was accompanied by labeling from other VIIIth nerve components 2,3. Here, we describe a method for anterograde tracing from the acoustic ganglion to selectively label auditory axons within the developing VIIIth nerve. First, after partial dissection of the anterior cephalic region of an 8-day chick embryo immersed in oxygenated artificial cerebrospinal fluid, the cochlear duct is identified by anatomical landmarks. Next, a fine pulled glass micropipette is positioned to inject a small amount of rhodamine dextran amine into the duct and adjacent deep region where the acoustic ganglion cells are located. Within thirty minutes following the injection, auditory axons are traced centrally into the hindbrain and can later be visualized following histologic preparation. This method provides a useful tool for developmental studies of peripheral to central auditory circuit formation. PMID:23542875
Repair of sciatic nerve defects using tissue engineered nerves
Zhang, Caishun; Lv, Gang
In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects. PMID:25206507
A Model for Functional Recovery and Cortical Reintegration after Hemifacial Composite Tissue Allotransplantation
Washington, Kia M.; Solari, Mario G.; Sacks, Justin M.; Horibe, Elaine K.; Unadkat, Jignesh V.; Carvell, George E.; Simons, Daniel J.; Lee, W. P. Andrew
Background The ability to achieve optimal functional recovery is important in both face and hand transplantation. The purpose of this study was to develop a functional rat hemifacial transplant model optimal for studying both functional outcome and cortical reintegration in composite tissue allotransplantation. Methods Five syngeneic transplants with motor and sensory nerve appositions (group 1) and five syngeneic transplants without nerve appositions (group 2) were performed. Five allogeneic transplants were performed with motor and sensory nerve appositions (group 3). Lewis (RT1l) rats were used for syngeneic transplants and Brown-Norway (RT1n) donors and Lewis (RT1l) recipients were used for allogeneic transplants. Allografts received cyclosporine A monotherapy. Functional recovery was assessed by recordings of nerve conduction velocity and cortical neural activity evoked by facial nerve and sensory (tactile) stimuli, respectively. Results All animals in groups 1 and 3 showed evidence of motor function return on nerve conduction testing, whereas animals in group 2, which did not have nerve appositions, did not show electrical activity on electromyographic analysis (p < 0.001). All animals in groups 1 and 3 showed evidence of reafferentation on recording from the somatosensory cortex after whisker stimulation. Animals in group 2 did not show a cortical response on stimulation of the whiskers (p < 0.001). Conclusion The authors have established a hemiface transplant model in the rat that has several modalities for the comprehensive study of motor and sensory recovery and cortical reintegration after composite tissue allotransplantation. PMID:19182661
Effect of low-intensity millimeter-range electromagnetic irradiation on the recovery of function in lesioned sciatic nerves in rats
L. I. Kolosova; G. N. Akoev; O. V. Ryabchikova; V. D. Avelev
The effects of electromagnetic irradiation (EMI) of wavelength 5.6 mm (frequency 53.57 GHz) and power density 4 mW\\/cm2 on the recovery of function in damaged rat sciatic nerve were studied; damage was produced by nerve section followed by microsuturing.\\u000a Irradiation was applied to the skin of the thigh in the area of suturing. Total action potential (TAP) recording from the
Rapid development of Purkinje cell excitability, functional cerebellar circuit, and afferent sensory input to cerebellum in zebrafish
Hsieh, Jui-Yi; Ulrich, Brittany; Issa, Fadi A.; Wan, Jijun; Papazian, Diane M.
The zebrafish has significant advantages for studying the morphological development of the brain. However, little is known about the functional development of the zebrafish brain. We used patch clamp electrophysiology in live animals to investigate the emergence of excitability in cerebellar Purkinje cells, functional maturation of the cerebellar circuit, and establishment of sensory input to the cerebellum. Purkinje cells are born at 3 days post-fertilization (dpf). By 4 dpf, Purkinje cells spontaneously fired action potentials in an irregular pattern. By 5 dpf, the frequency and regularity of tonic firing had increased significantly and most cells fired complex spikes in response to climbing fiber activation. Our data suggest that, as in mammals, Purkinje cells are initially innervated by multiple climbing fibers that are winnowed to a single input. To probe the development of functional sensory input to the cerebellum, we investigated the response of Purkinje cells to a visual stimulus consisting of a rapid change in light intensity. At 4 dpf, sudden darkness increased the rate of tonic firing, suggesting that afferent pathways carrying visual information are already active by this stage. By 5 dpf, visual stimuli also activated climbing fibers, increasing the frequency of complex spiking. Our results indicate that the electrical properties of zebrafish and mammalian Purkinje cells are highly conserved and suggest that the same ion channels, Nav1.6 and Kv3.3, underlie spontaneous pacemaking activity. Interestingly, functional development of the cerebellum is temporally correlated with the emergence of complex, visually-guided behaviors such as prey capture. Because of the rapid formation of an electrically-active cerebellum, optical transparency, and ease of genetic manipulation, the zebrafish has great potential for functionally mapping cerebellar afferent and efferent pathways and for investigating cerebellar control of motor behavior. PMID:25565973
Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair
There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986
Impaired peripheral somatosensory function in children with Down syndrome.
Brandt, B R; Rosén, I
Sensory neurography of the median nerve was performed bilaterally in 6 children with Down syndrome (DS) aged 11-16 years and in 10 healthy controls of similar age. The sensory nerve conduction velocities from the thumbs and 3rd fingers were recorded and were significantly subnormal in the DS group. Sensory nerve action potentials were also lower in the DS children and the difference was particularly evident following stimuli of the thumbs. Using scalp electrodes sensory evoked potential latencies were recorded in five of the DS children and all controls. There was no obvious difference between the subjects with DS and the controls. It is suggested that an impaired peripheral somatosensory function should be added to previously known symptoms constituting DS. The results may contribute to previous findings of a poor performance of DS children in tests of tactual perception. PMID:8719746
Analysis and Measurement of the Sympathetic and Sensory Innervation of White and Brown Adipose Tissue
Vaughan, Cheryl H.; Zarebidaki, Eleen; Ehlen, J. Christopher; Bartness, Timothy J.
Here, we provide a detailed account of how to denervate white and brown adipose tissue (WAT and BAT) and how to measure sympathetic nervous system (SNS) activity to these and other tissues neurochemically. The brain controls many of the functions of WAT and BAT via the SNS innervation of the tissues, especially lipolysis and thermogenesis, respectively. There is no clearly demonstrated parasympathetic innervation of WAT or the major interscapular BAT (IBAT) depot. WAT and BAT communicate with the brain neurally via sensory nerves. We detail the surgical denervation (eliminating both innervations) of several WAT pads and IBAT. We also detail more selective chemical denervation of the SNS innervation via intra-WAT/IBAT 6-hydroxy-dopamine (a catecholaminergic neurotoxin) injections and selective chemical sensory denervation via intra-WAT/IBAT capsaicin (a sensory nerve neurotoxin) injections. Verifications of the denervations are provided (HPLC-EC detection for SNS, ELIA for calcitonin gene-related peptide (proven sensory nerve marker)). Finally, assessment of the SNS drive to WAT/BAT or other tissues is described using the alpha-methyl-para-tyrosine method combined with HPLC-EC, a direct neurochemical measure of SNS activity. These methods have proven useful for us and for other investigators interested in innervation of adipose tissues. The chemical denervation approach has been extended to nonadipose tissues as well. PMID:24480348
Combined enriched environment÷atipamezole treatment transiently improves sensory functions in stroke rats independent from neurogenesis and angiogenesis.
Kuptsova, Kristina; Kvist, Elisabet; Nitzsche, Franziska; Jolkkonen, Jukka
Functional recovery after cerebral ischemia may be enhanced by activation of the noradrenergic system and by environmental enrichment. The underlying mechanisms have remained elusive, but endogenous neurogenesis and perilesional angiogenesis have been speculated to contribute to the behavioral improvement. To address this question, neurogenesis in the subventricular zone (SVZ) and perilesional angiogenesis (RECA-1) were correlated with behavioral performance in forty Wistar rats subjected to transient middle cerebral artery occlusion (MCAO) or sham-operation. Atipamezole, an ?2-adrenoreceptor antagonist (1 mg÷kg, i.p.), was administered for 10 days together with housing of rats in an enriched environment. MCAO rats and sham-operated rats housed in single non-enriched cages were used as controls. Histological analysis after 28-day behavioral follow-up showed a massive increase in doublecortin (DCX)-positive cells in the SVZ both in MCAO rats housed in single cages and in the enriched environment together with atipamezole treatment whereas perilesional RECA-1 staining for new blood vessels was not altered. Time to the first contact and time to remove sticky stimuli from the forelimbs indicated improved sensory processing, which disappeared after cessation of atipamezole administration. Skilled forelimb use as measured by performance in Montoya's staircase test was not affected by the treatment. There were no correlations between behavioral measures and histology. Thus, sensory facilitation or reversal of hypometabolism by the combined therapy may be the mechanism accounting for the improved behavior after stroke independent from neurogenesis and angiogenesis. PMID:25826486
Sensory experience during locomotion promotes recovery of function in adult visual cortex.
Kaneko, Megumi; Stryker, Michael P
Recovery from sensory deprivation is slow and incomplete in adult visual cortex. In this study, we show that visual stimulation during locomotion, which increases the gain of visual responses in primary visual cortex, dramatically enhances recovery in the mouse. Excitatory neurons regained normal levels of response, while narrow-spiking (inhibitory) neurons remained less active. Visual stimulation or locomotion alone did not enhance recovery. Responses to the particular visual stimuli viewed by the animal during locomotion recovered, while those to another normally effective stimulus did not, suggesting that locomotion promotes the recovery only of the neural circuits that are activated concurrent with the locomotion. These findings may provide an avenue for improving recovery from amblyopia in humans.DOI: http://dx.doi.org/10.7554/eLife.02798.001. PMID:24970838
Adipose derived stem cells and nerve regeneration
Faroni, Alessandro; Smith, Richard JP; Reid, Adam J
Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts. PMID:25221589
Gray, W P; Keohane, C; Kirwan, W O
The motor nerve transplantation (MNT) technique is used to transfer an intact nerve into a denervated muscle by harvesting a neurovascular pedicle of muscle containing motor endplates from the motor endplate zone of a donor muscle and implanting it into a denervated muscle. Thirty-six adult New Zealand White rabbits underwent reinnervation of the left long peroneal (LP) muscle (fast twitch) with a motor nerve graft from the soleus muscle (slow twitch). The right LP muscle served as a control. Reinnervation was assessed using microstimulatory single-fiber electromyography (SFEMG), alterations in muscle fiber typing and grouping, and isometric response curves. Neurofilament antibody was used for axon staining. The neurofilament studies provided direct evidence of nerve growth from the motor nerve graft into the adjacent denervated muscle. Median motor endplate jitter was 13 microsec preoperatively, and 26 microsec at 2 months, 29.5 microsec at 4 months, and 14 microsec at 6 months postoperatively (p < 0.001). Isometric tetanic tension studies showed a progressive functional recovery in the reinnervated muscle over 6 months. There was no histological evidence of aberrant reinnervation from any source outside the nerve pedicle. Isometric twitch responses and adenosine triphosphatase studies confirmed the conversion of the reinnervated LP muscle to a slow-type muscle. Acetylcholinesterase studies confirmed the presence of functioning motor endplates beneath the insertion of the motor nerve graft. It is concluded that the MNT technique achieves motor reinnervation by growth of new nerve fibers across the pedicle graft into the recipient muscle. PMID:9322851
K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model
Siba P. Raychaudhuri; Mrinmoy Sanyal; Helena Weltman; Smriti Kundu-Raychaudhuri
The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased
The properties, distribution and function of Na(+)-Ca(2+) exchanger isoforms in rat cutaneous sensory neurons.
Scheff, N N; Yilmaz, E; Gold, M S
The Na(+)-Ca(2+) exchanger (NCX) appears to play an important role in the regulation of the high K(+)-evoked Ca(2+) transient in putative nociceptive dorsal root ganglion (DRG) neurons. The purpose of the present study was to (1) characterize the properties of NCX activity in subpopulations of DRG neurons, (2) identify the isoform(s) underlying NCX activity, and (3) begin to assess the function of the isoform(s) in vivo. In retrogradely labelled neurons from the glabrous skin of adult male Sprague-Dawley rats, NCX activity, as assessed with fura-2-based microfluorimetry, was only detected in putative nociceptive IB4+ neurons. There were two modes of NCX activity: one was evoked in response to relatively large and long lasting (?325 nm for >12 s) increases in the concentration of intracellular Ca(2+) ([Ca(2+)]i), and a second was active at resting [Ca(2+)]i > ?150 nm. There also were two modes of evoked activity: one that decayed relatively rapidly (<5 min) and a second that persisted (>10 min). Whereas mRNA encoding all three NCX isoforms (NCX1-3) was detected in putative nociceptive cutaneous neurons with single cell PCR, pharmacological analysis and small interfering RNA (siRNA) knockdown of each isoform in vivo suggested that NCX2 and 3 were responsible for NCX activity. Western blot analyses suggested that NCX isoforms were differentially distributed within sensory neurons. Functional assays of excitability, action potential propagation, and nociceptive behaviour suggest NCX activity has little influence on excitability per se, but instead influences axonal conduction velocity, resting membrane potential, and nociceptive threshold. Together these results indicate that the function of NCX in the regulation of [Ca(2+)]i in putative nociceptive neurons may be unique relative to other cells in which these exchanger isoforms have been characterized and it has the potential to influence sensory neuron properties at multiple levels. PMID:25239455
Transient receptor potential V2 expressed in sensory neurons is activated by probenecid
Sangsu Bang; Kyung Yoon Kim; Sungjae Yoo; Sang-Heon Lee; Sun Wook Hwang
Temperature-activated transient receptor potential ion channels (thermoTRPs) are known to function as ambient temperature sensors and are also involved in peripheral pain sensation. The thermoTRPs are activated by a variety of chemicals, of which specific activators have been utilized to explore the physiology of particular channels and sensory nerve subtypes. The use of capsaicin for TRPV1 is an exemplary case
Neurotrophin3 Administration Attenuates Deficits of Pyridoxine-Induced Large-Fiber Sensory Neuropathy
Maureen E. Helgren; Kenneth D. Cliffer; Kim Torrento; Chris Cavnor; Rory Curtis; Peter S. DiStefano; Stanley J. Wiegand; Ronald M. Lindsay
Chronic treatment of adult rats for 2-3 weeks with high doses of pyridoxine (vitamin B6) produced a profound proprioceptive loss, similar to that found in humans overdosed with this vita- min or treated with the chemotherapeutic agent cisplatin. Pyr- idoxine toxicity was manifest as deficits in simple and precise locomotion and sensory nerve function and as degeneration of large-diameter\\/large-fiber spinal
Two-Point Discrimination Test of the Skin as an Index of Sensory Aging
H. Shimokata; F. Kuzuya
Although the two-point discrimination test of the skin is a simple test of the sensory nerve function, there have been few studies on age-related changes in the ability to discriminate between two points in a large noninstitutionalized population. In this study we attempted (1) to determine normal values on the two-point discrimination test by age and gender in a large
Estimation of the neuromotor system functional state after sciatic nerve neurorrhaphy in experimental conditions of intravenous laser irradiation of blood
NASA Astrophysics Data System (ADS)
Nechipurenko, N. I.; Tanin, Leonid V.; Antonov, Ignatii P.; Vasilevskaya, Lyudmila A.; Vlasyuk, P. A.
The speckle-optical methods and the methods of electroneuromyography were used to study the myotonus, the contractional activity of leg muscles and the neuromotor system functional state in intact rabbits and 3 months after the sciatic nerve (SN) neurorrhaphy in conditions of intravenous laser irradiation of blood (ILIB). The blood of animals was exposed to laser radiation with the help of a quartz-polymeric light guide, which has been inserted into the earvein the next day after SN stitching. The radiation power at the light guide output was 2-2.5 mW. Two courses of treatment with a two-week interval have been conducted. It has been established from the speckle-optical study data that ILIB increases the contractional activity of skeletal muscles in animals. The ILIB-therapy after the SN neurorrhaphy normalizes the latent period of M-response and neural cation potential. A tendancy has been revealed to an increase in impulse conduction velocity in motor nerve fibers and in maximal amplitude of the neural action potential. Thus, the ILIB-therapy after SN trauma improves the neuromotor system functional state in experimental animals in the early reinnervation period.
Suprascapular Nerve Block for Postoperative Pain Relief in Arthroscopic Shoulder Surgery: A New Modality?
DENISE J. WEDEL; Ewan D. Ritchie; Doris Tong; Frances Chung; Andrew M. Norris; Anthony Miniaci
effects, and intraarticular local anesthetic has been shown to be ineffective when used for postoperative pain relief. The suprascapular nerve supplies 70% of the sensory nerve supply to the shoulder joint, and local anesthetic block of this nerve is effective in cer- tain shoulder pain disorders. To determine the effi- cacy of a suprascapular nerve block, subcutaneous saline was compared
Ulnar nerve reconstruction with an expanded polytetrafluoroethylene conduit.
Stanec, S; Stanec, Z
The ulnar nerve of a 22-year-old woman was reconstructed by expanded polytetrafluoroethylene (ePTFE) conduit, 141 days after nerve transection at the distal forearm level. A 2.9 cm nerve gap was bridged by a corrugated, 3.9 cm long, 6 mm diameter ePTFE tube. At final evaluation 3 years later the patient achieved excellent motor and sensory recovery. Exploration of the tube, at that time, showed macroscopically normal nerve inside the conduit. PMID:10209470
Sciatic nerve regeneration is not inhibited by anti-NGF antibody treatment in the adult rat.
Lankford, K L; Arroyo, E J; Liu, C-N; Somps, C J; Zorbas, M A; Shelton, D L; Evans, M G; Hurst, S I; Kocsis, J D
Elevated nerve growth factor (NGF) is believed to play a role in many types of pain. An NGF-blocking antibody (muMab 911) has been shown to reduce pain and hyperalgesia in pain models, suggesting a novel therapeutic approach for pain management. Since NGF also plays important roles in peripheral nervous system development and sensory nerve outgrowth, we asked whether anti-NGF antibodies would adversely impact peripheral nerve regeneration. Adult rats underwent a unilateral sciatic nerve crush to transect axons and were subcutaneously dosed weekly for 8weeks with muMab 911 or vehicle beginning 1day prior to injury. Plasma levels of muMab 911 were assessed from blood samples and foot print analysis was used to assess functional recovery. At 8-weeks post-nerve injury, sciatic nerves were prepared for light and electron microscopy. In a separate group, Fluro-Gold was injected subcutaneously at the ankle prior to perfusion, and counts and sizes of retrogradely labeled and unlabeled dorsal root ganglion neurons were obtained. There was no difference in the time course of gait recovery in antibody-treated and vehicle-treated animals. The number of myelinated and nonmyelinated axons was the same in the muMab 911-treated crushed nerves and intact nerves, consistent with observed complete recovery. Treatment with muMab 911 did however result in a small decrease in average cell body size on both the intact and injured sides. These results indicate that muMab 911 did not impair functional recovery or nerve regeneration after nerve injury in adult rats. PMID:23531437
Quality and sensory acceptability of a chilled functional apple ready-dessert.
Keenan, D F; Brunton, N P; Gormley, T R; Butler, F
An apple and dairy based ready-dessert with an added prebiotic was stored and chill temperatures and number of quality attributes were monitored during chill (4?°C) storage for 30 days. All ready-desserts were thermally processed by sous vide (P (90)?>?10 min). The stability of the dairy component in ready-desserts was monitored by measuring volatile free fatty acids. Changes in these components were more evident in prebiotic-enriched samples compared to controls. However, no significant differences were observed over storage in control and prebiotic-enriched ready-desserts. This was supported by sensory analysis that showed no significant changes over storage in control or prebiotic-enriched samples. Of the other quality parameters, the addition of prebiotic inclusions resulted in lower L and b values and dry matter (p?0.05), while increasing (p?0.05) soluble solids content compared to control samples. Fluctuations in some of the quality parameters were also observed over storage. Rheological characteristics, i.e. flow behaviour (n), consistency index (K), storage (G'), loss (G?) and complex (G*) moduli were unaffected by prebiotic inclusion. However, storage affected the rheological characteristics of ready-desserts. A decrease (p?0.05) in flow behaviour (n) led to concomitant increases in consistency index (K) and complex modulus (G*) values in control samples. PMID:22407955
C. elegans ciliated sensory neurons release extracellular vesicles that function in animal communication.
Wang, Juan; Silva, Malan; Haas, Leonard A; Morsci, Natalia S; Nguyen, Ken C Q; Hall, David H; Barr, Maureen M
Cells release extracellular vesicles (ECVs) that play important roles in intercellular communication and may mediate a broad range of physiological and pathological processes. Many fundamental aspects of ECV biogenesis and signaling have yet to be determined, with ECV detection being a challenge and obstacle due to the small size (100 nm) of the ECVs. We developed an in vivo system to visualize the dynamic release of GFP-labeled ECVs. We show here that specific Caenorhabdidits elegans ciliated sensory neurons shed and release ECVs containing GFP-tagged polycystins LOV-1 and PKD-2. These ECVs are also abundant in the lumen surrounding the cilium. Electron tomography and genetic analysis indicate that ECV biogenesis occurs via budding from the plasma membrane at the ciliary base and not via fusion of multivesicular bodies. Intraflagellar transport and kinesin-3 KLP-6 are required for environmental release of PKD-2::GFP-containing ECVs. ECVs isolated from wild-type animals induce male tail-chasing behavior, while ECVs isolated from klp-6 animals and lacking PKD-2::GFP do not. We conclude that environmentally released ECVs play a role in animal communication and mating-related behaviors. PMID:24530063
Chemical composition, functional and sensory characteristics of wheat-taro composite flours and biscuits.
Himeda, Makhlouf; Njintang Yanou, Nicolas; Fombang, Edith; Facho, Balaam; Kitissou, Pierre; Mbofung, Carl M F; Scher, Joel
The physicochemical, alveographic and sensory characteristics of precooked taro-wheat composite flours and their biscuits were investigated. A 2x7 factorial design consisting of two varieties of taro flour (Red Ibo Ngaoundere, RIN, and egg-like varieties) and 7 levels of wheat substitutions (0, 5, 10, 15, 20, 25 and 30 %) was used for this purpose. It was observed that water absorption capacity (range 95-152 g/100 g), water solubility index (range 18.8-29.5 g/100 g) and swelling capacity (range 125.4-204.6 mL/100 g) of composite flours significantly (p?0.05) increased with increase in taro level. Conversely the dough elasticity index (range 59.8-0 %), extensibility (78-22 mm) and strength (range 281-139?×?10(-4) joules) significantly (p?0.05) diminished with increase in wheat substitution. Up to 10 % substitution with RIN taro flour and 15 % with egg-like taro flour, the composite taro-wheat dough exhibited elasticity indices acceptable for the production of baking products, whereas at all levels of taro substitution, the composite biscuits samples were either acceptable as or better (5-10 % substitution with RIN flour) than 100 % wheat biscuit. PMID:25190844
Radiation-induced changes in peripheral nerve by stereotactic radiosurgery: a study on the sciatic nerve of rabbit.
Lin, Zhixiong; Wu, Vincent W C; Ju, Wenchui; Yamada, Yoshiya; Chen, Longhua
A large fractional dose in radiotherapy produces better radiobiological results, but there is always a concern of radiation-induced damage to the normal tissues, especially peripheral nerves. This study was to evaluate the radiation-induced changes of sciatic nerve treated by stereotactic radiosurgery (SRS) in rabbit. A localization test was performed on 3 rabbits to determine the reference landmarks to the location of the sciatic nerve of rabbit in CT. Another 12 rabbits were irradiated by a dose of 25 Gy at the sciatic nerve using SRS with 5 non-coplanar arcs. The rabbits were randomized into 3 groups and euthanised at 3, 5, and 7 months after radiotherapy, respectively. Apart from the sensory and motor tests performed on the rabbits, segments of the sciatic nerve were prepared for hematoxylin and eosin staining. Histologic and ultra-structural examinations including morphometric analyses were conducted and compared with the control (non-irradiated side). Apart from the loosening of myelin layers at 5 months, no prominent changes were shown at 3 and 5 months after irradiation. At 7 months, despite the fact that the sensation and motor function tests remained intact, ultra-structural examination showed obvious vacuolation, degeneration and necrosis of the axons with myelin fragmentation. In addition, morphometric analysis indicated that, when compared with the control, there was significant reduction in fiber diameter, increase of myelin thickness and decrease of G ratio (P < 0.01). Although it remained functionally intact, a focal single dose of 25 Gy caused significant microscopic damage to the rabbit sciatic nerve at 7 months after irradiation. Escalating doses with large single fractional dose involving peripheral nerves should be carried out with caution. PMID:20652361
Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve.
Sarabia-Estrada, Rachel; Bańuelos-Pineda, Jacinto; Osuna Carrasco, Laura P; Jiménez-Vallejo, Salvador; Jiménez-Estrada, Ismael; Rivas-Celis, Efrain; Dueńas-Jiménez, Judith M; Dueńas-Jiménez, Sergio H
OBJECT Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. METHODS After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. RESULTS At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes. Some gastrocnemius efferent fibers were partially repaired 90 days after nerve resection. The better outcome in knee angle displacement may be partially attributable to the aberrant neuromuscular synaptic effects, since nerve conduction in the gastrocnemius muscle could be blocked in the progesterone-impregnated chitosan tubes. In addition, in the region of the gap produced by the nerve resection, the number of axons and amount of myelination were reduced in the sciatic nerve implanted with chitosan, progesterone-loaded chitosan, and silicone tubes. At 180 days after sciatic nerve sectioning, the knee kinematic function recovered to a level observed in control rats of a similar age. In rats with progesterone-loaded chitosan tubes, stimulation of the proximal and intratubular sciatic nerve segments produced an electromyographic response. The axon morphology of the proximal and intratubular segments of the sciatic nerve resembled that of the contralateral nontransected nerve. CONCLUSIONS Progesterone-impregnated chitosan tubes produced aberrant innervation of the gastrocnemius muscle, which allowed partial recovery of gait locomotion and could be adequate for reinnervating synergistic denervated muscles while a parent innervation is reestablished. Hindlimb kinematic parameters differed between younger (those at 90 days) and older (those at 180 days) rats. PMID:25679274
Application and histology-driven refinement of active contour models to functional region and nerve delineation: towards a digital brainstem atlas
NASA Astrophysics Data System (ADS)
Patel, Nirmal; Sultana, Sharmin; Rashid, Tanweer; Krusienski, Dean; Audette, Michel A.
This paper presents a methodology for the digital formatting of a printed atlas of the brainstem and the delineation of cranial nerves from this digital atlas. It also describes on-going work on the 3D resampling and refinement of the 2D functional regions and nerve contours. In MRI-based anatomical modeling for neurosurgery planning and simulation, the complexity of the functional anatomy entails a digital atlas approach, rather than less descriptive voxel or surface-based approaches. However, there is an insufficiency of descriptive digital atlases, in particular of the brainstem. Our approach proceeds from a series of numbered, contour-based sketches coinciding with slices of the brainstem featuring both closed and open contours. The closed contours coincide with functionally relevant regions, whereby our objective is to fill in each corresponding label, which is analogous to painting numbered regions in a paint-by-numbers kit. Any open contour typically coincides with a cranial nerve. This 2D phase is needed in order to produce densely labeled regions that can be stacked to produce 3D regions, as well as identifying the embedded paths and outer attachment points of cranial nerves. Cranial nerves are modeled using an explicit contour based technique called 1-Simplex. The relevance of cranial nerves modeling of this project is two-fold: i) this atlas will fill a void left by the brain segmentation communities, as no suitable digital atlas of the brainstem exists, and ii) this atlas is necessary to make explicit the attachment points of major nerves (except I and II) having a cranial origin. Keywords: digital atlas, contour models, surface models
Sensory TRP channels: the key transducers of nociception and pain.
Mickle, Aaron D; Shepherd, Andrew J; Mohapatra, Durga P
Peripheral detection of nociceptive and painful stimuli by sensory neurons involves a complex repertoire of molecular detectors and/or transducers on distinct subsets of nerve fibers. The majority of such molecular detectors/transducers belong to the transient receptor potential (TRP) family of cation channels, which comprise both specific receptors for distinct nociceptive stimuli, as well as for multiple stimuli. This chapter discusses the classification, distribution, and functional properties of individual TRP channel types that have been implicated in various nociceptive and/or painful conditions. PMID:25744671
Dicer-microRNA pathway is critical for peripheral nerve regeneration and functional recovery in vivo and regenerative axonogenesis in vitro
Wu, Di; Raafat, Abdalla; Pak, Elena; Clemens, Stefan; Murashov, Alexander K.
Both central and peripheral axons contain pivotal microRNA (miRNA) proteins. While recent observation demonstrated that miRNA biosynthetic machinery responds to peripheral nerve lesion in an injury-regulated pattern, the physiological significance of this phenomenon remains to be elucidated. In the current paper we hypothesized that deletion of Dicer would disrupt production of Dicer-dependent miRNAs and would negatively impact regenerative axon growth. Taking advantage of tamoxifen-inducible CAG-CreERt:Dicerfl/fl knockout (Dicer KO), we investigated the results of Dicer deletion on sciatic nerve regeneration in vivo and regenerative axon growth in vitro. Here we show that the sciatic functional index, an indicator of functional recovery, was significantly lower in Dicer KO mice in comparison to wild-type animals. Restoration of mechanical sensitivity recorded in the von Frey test was also markedly impaired in Dicer mutants. Further, Dicer deletion impeded the recovery of nerve conduction velocity and amplitude of evoked compound action potentials in vitro. Histologically, both total number of regenerating nerve fibers and mean axonal area were notably smaller in the Dicer KO mice. In addition, Dicer-deficient neurons failed to regenerate axons in dissociated dorsal root ganglia (DRG) cultures. Taken together, our results demonstrate that knockout of Dicer clearly impedes regenerative axon growth as well as anatomical, physiological and functional recovery. Our data suggest that the intact Dicer-dependent miRNA pathway is critical for the successful peripheral nerve regeneration after injury. PMID:22178326
Uncultured undifferentiated adipose-derived nucleated cell fractions combined with inside-out artery graft accelerate sciatic nerve regeneration and functional recovery.
Mohammadi, R; Asadollahi, A; Amini, K
Effects of transplantation of adipose-derived nucleated cell fractions (ADNCs) on sciatic nerve regeneration were studied. A 10-mm sciatic nerve defect was bridged using artery graft filled with ADNCs. In control group, artery graft was filled with saline alone. Regenerated nerve fibres were studied for 12 weeks. In sham-operated group, sciatic nerve was only exposed and manipulated. Behavioural and functional studies confirmed faster recovery of regenerated axons in ADNCs transplanted animals than in control group (P<0.05). At the end of study period, animals in ADNCs transplanted group achieved a sciatic functional index (SFI) value of -31.6 ± -3.14, whereas in control group a value of -42.5 ± -3.7 was found. Gastrocnemius muscle mass in ADNCs transplanted animals was found to be significantly higher than that in control group (P=0.001). Morphometric indices of regenerated fibres showed the number and diameter of myelinated fibres to be significantly higher in ADNCs transplanted animals than in control group (P=0.001). On immunohistochemistry, there was more positive staining of S100 in the ADNCs transplanted animals than in control group. ADNCs transplantation into an artery graft could be considered a readily accessible technique that improves functional recovery of sciatic nerve. PMID:24951175
Sensory and sympathetic nervous system control of white adipose tissue lipolysis
Bartness, Timothy J.; B., Shrestha, Y.; H., Vaughan, C.; J., Schwartz, G.; K., Song, C.
Summary Circulating factors are typically invoked to explain bidirectional communication between the CNS and white adipose tissue (WAT). Thus, initiation of lipolysis has been relegated primarily to adrenal medullary secreted catecholamines and the inhibition of lipolysis primarily to pancreatic insulin, whereas signals of body fat levels to the brain have been ascribed to adipokines such as leptin. By contrast, evidence is given for bidirectional communication between brain and WAT occurring via the sympathetic nervous system (SNS) and sensory innervation of this tissue. Using retrograde transneuronal viral tract tracers, the SNS outflow from brain to WAT has been defined. Functionally, sympathetic denervation of WAT blocks lipolysis to a variety of lipolytic stimuli. Using anterograde transneuronal viral tract tracers, the sensory input from WAT to brain has been defined. Functionally, these WAT sensory nerves respond electrophysiologically to increases in WAT SNS drive suggesting a possible neural negative feedback loop to regulate lipolysis. PMID:19747957
Evaluation and use of regenerative multi electrode interfaces in peripheral nerves
NASA Astrophysics Data System (ADS)
Desai, Vidhi
Peripheral nerves offer unique accessibility to the innate motor and sensory pathways that can be interfaced with high degree of selectivity for intuitive and bidirectional control of advanced upper extremity prosthetic limbs. Several peripheral nerve interfaces have been proposed and investigated over the last few decades with significant progress made in the area of sensory feedback. However, clinical translation still remains a formidable challenge due to the lack of long term recordings. Prominent causes include signal degradation, eventual interface failures, and lack of specificity in the low amplitude nerve signals. This dissertation evaluates the capabilities of the newly developed Regenerative Multi-electrode Interface (REMI) by the characterization of signal quality progression, the identification of interfaced axon types, and the demonstration of "functional linkage" between acquired signals and target organs. Chapter 2 details the chronic recording of high quality signals from REMI in sciatic nerve which remained stable over a 120 day implantation period indicative of minimal ongoing tissue response with no detrimental effects on the recording ability. The dominant cause of failures was attributable to abiotic factors pertaining to the connector/wire breakage, observed in 76% of REMI implants. Also, the REMI implants had 20% higher success rate and significantly larger Signal to Noise Ratio (SNR) in comparison to the Utah Slanted Electrode Array (USEA). Chapter 3 describes the successful feasibility of interfacing with motor and sensory axons by REMI implantation in the tibial and sural fascicles of the sciatic nerve. A characteristic sampling bias towards recording signals from medium-to-large diameter axons that are primarily involved in mechanoception and proprioception sensory functions was uncovered. Specific bursting units (Inter Spike Interval of 30-70ms) were observed most frequently from the tibial fascicle during bipedal locomotion. Chapter 4 explores the discrimination between motor and proprioceptive origin of this bursting activity and reports the identified efferent motor nature, as well as the demonstration of a significant and stable correlation with the activity of distal muscle involved in locomotion. In summary, sensory-motor neural activity was recorded chronically by REMI electrodes with high SNR which serves as a tool for evaluating firing patterns of specific axon types during voluntary movement or sensory stimulation. In turn, this interface can be used to improve motor control and sensory feedback in closed loop systems for robotic prosthesis.
Mass Spectrometry Imaging and GC-MS Profiling of the Mammalian Peripheral Sensory-Motor Circuit
NASA Astrophysics Data System (ADS)
Rubakhin, Stanislav S.; Ulanov, Alexander; Sweedler, Jonathan V.
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has evolved to become an effective discovery tool in science and clinical diagnostics. Here, chemical imaging approaches are applied to well-defined regions of the mammalian peripheral sensory-motor system, including the dorsal root ganglia (DRG) and adjacent nerves. By combining several MSI approaches, analyte coverage is increased and 195 distinct molecular features are observed. Principal component analysis suggests three chemically different regions within the sensory-motor system, with the DRG and adjacent nerve regions being the most distinct. Investigation of these regions using gas chromatography-mass spectrometry corroborate these findings and reveal important metabolic markers related to the observed differences. The heterogeneity of the structurally, physiologically, and functionally connected regions demonstrates the intricate chemical and spatial regulation of their chemical composition.
Sensory Processing Abilities and Their Relation to Participation in Leisure Activities among Children with High-Functioning Autism Spectrum Disorder (HFASD)
ERIC Educational Resources Information Center
Hochhauser, Michal; Engel-Yeger, Batya
Children with autism may have atypical sensory processing abilities, which are known to impact child's performance and participation. However, lack of information exists regarding the expression of these abilities in specific groups on the spectrum, as children with high-functioning autism spectrum disorder (HFASD). This study aimed to…
Exploring Structural Dynamics within and between Sensory and Intellectual Functioning in Old and Very Old Age: Longitudinal Evidence from the Berlin Aging Study
ERIC Educational Resources Information Center
Ghisletta, Paolo; Lindenberger, Ulman
Cross-sectional and longitudinal analyses of age-heterogeneous samples have revealed correlational links between and within intellectual, sensory, and sensorimotor domains. Due to basic limitations of cross-sectional designs and a reluctance to disentangle antecedent-consequent relations in longitudinal designs, the functional significance and…
An autocrine neuronal interleukin-6 loop mediates chloride accumulation and NKCC1 phosphorylation in axotomized sensory neurons.
Pieraut, Simon; Lucas, Olivier; Sangari, Sina; Sar, Chamroeun; Boudes, Mathieu; Bouffi, Carine; Noel, Daničle; Scamps, Frédérique
The cation-chloride cotransporter NKCC1 plays a fundamental role in the central and peripheral nervous systems by setting the value of intracellular chloride concentration. Following peripheral nerve injury, NKCC1 phosphorylation-induced chloride accumulation contributes to neurite regrowth of sensory neurons. However, the molecules and signaling pathways that regulate NKCC1 activity remain to be identified. Functional analysis of cotransporter activity revealed that inhibition of endogenously produced cytokine interleukin-6 (IL-6), with anti-mouse IL-6 antibody or in IL-6?/? mice, prevented chloride accumulation in a subset of axotomized neurons. Nerve injury upregulated the transcript and protein levels of IL-6 receptor in myelinated, TrkB-positive sensory neurons of murine lumbar dorsal root ganglia. Expression of phospho-NKCC1 was observed mainly in sensory neurons expressing IL-6 receptor and was absent from IL-6?/? dorsal root ganglia. The use of IL-6 receptor blocking-function antibody or soluble IL-6 receptor, together with pharmacological inhibition of Janus kinase, confirmed the role of neuronal IL-6 signaling in chloride accumulation and neurite growth of a subset of axotomized sensory neurons. Cell-specific expression of interleukin-6 receptor under pathophysiological conditions is therefore a cellular response by which IL-6 contributes to nerve regeneration through neuronal NKCC1 phosphorylation and chloride accumulation. PMID:21940443
Theobromine inhibits sensory nerve activation and cough
Omar S. Usmani; Maria G. Belvisi; Hema J. Patel; Natascia Crispino; Mark A. Birrell; Márta Korbonits; Peter J. Barnes
Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid- induced cough in guinea-pigs in vivo. Furthermore,
Differential distribution of thyroid hormone receptor isoform in rat dorsal root ganglia and sciatic nerve in vivo and in vitro.
Glauser, L; Barakat Walter, I
Using autoradiographic techniques carried out under precise conditions we previously demonstrated that both sensory neurons and peripheral glial cells in dorsal root ganglia (DRG) or sciatic nerve, possess specific [125I]-labeled T3 binding sites. Thyroid hormone receptors (TR) include several isoforms (TR alpha(1), TR alpha(2), TR beta(1), TR beta(2...)) The present study demonstrates that while sensory neurons and peripheral glial cells both possess functional TR, they express a differential expression of TR isoforms. Using a panel of antisera to specific for the TR alpha-common (alpha(1) and alpha(2)), TR alpha-1 or TR beta-1 isoforms, we detected TRs isoform localization at the cellular level during DRG and sciatic nerve development and regeneration. Immunohistochemical analysis revealed that during embryonic life, sensory neurons express TR alpha-common and TR beta-1 rather than TR alpha-1. The number of TR alpha-common and TR beta-1 positive neurons as well as the intensity of labeling increased during the first two postnatal weeks and remained more or less stable in adult life. TR alpha-1 immunoreactivity, which was undetectable in embryonic sensory neurons, became discreetly visible in neurons after birth. In developing DRG and sciatic nerves, Schwann cells exhibited TR alpha-common and TR alpha-1 rather than TR beta-1 immunolabeling. The appearance of TR alpha-common and alpha-1 isoform immunoreactivity in the sciatic nerve was restricted to a short period ranging from E17 up to two postnatal weeks. By comparing TR alpha-common and TR alpha-1 immunostaining we can deduce that Schwann cells primarily express TR alpha-1. Afterwards, in adult rat sciatic nerve TR alpha isoforms was no more detected. However transection of sciatic nerve caused a reexpression of TR alpha isoforms in degenerating nerve. The prevalence of TR alpha in Schwann cells in vivo was correlated with in vitro results. The differential expression of TR alpha and beta by sensory neurons and Schwann cells indicates that the feedback regulation of circulating thyroid hormone could occur by binding to either the alpha or beta TR isoforms. Moreover, the presence of multiple receptor isoforms in developing sensory neurons suggests that thyroid hormone uses multiple signaling pathways to regulate DRG and sciatic nerve development. PMID:9089473
Macrophage-Mediated Dorsal Root Ganglion Damage Precedes Altered Nerve Conduction in SIV-Infected Macaques
Laast, Victoria A.; Shim, Beom; Johanek, Lisa M.; Dorsey, Jamie L.; Hauer, Peter E.; Tarwater, Patrick M.; Adams, Robert J.; Pardo, Carlos A.; McArthur, Justin C.; Ringkamp, Matthias; Mankowski, Joseph L.
Peripheral neuropathy is the most common neurological complication of HIV-1 infection, affecting over one-third of infected individuals, including those treated with antiretroviral therapy. To study the pathogenesis of HIV-induced peripheral nervous system disease, we established a model in which SIV-infected macaques developed changes closely resembling alterations reported in components of the sensory pathway in HIV-infected individuals. Significant declines in epidermal nerve fiber density developed in SIV-infected macaques, similar to that of HIV-infected individuals with neuropathy. Changes in dorsal root ganglia (DRG) included macrophage infiltration, SIV replication in macrophages, immune activation of satellite cells, and neuronal loss. To determine whether dorsal root ganglion damage was associated with altered nerve function, we measured unmyelinated C-fiber conduction velocities (CV) in nerves of SIV-infected macaques and compared CV changes with DRG alterations. Twelve weeks postinoculation, SIV-infected macaques had significantly lower C-fiber conduction velocity in sural nerves than uninfected animals and the magnitude of conduction velocity decline correlated strongly with extent of DRG macrophage infiltration. Thus, injury to neurons in the DRG—mediated by activated macrophages—preceded altered conduction of unmyelinated nerve fibers in SIV-infected macaques, suggesting that macrophage-mediated DRG damage may be the initiating event in HIV-induced sensory neuropathy. PMID:21924225
Far field potentials from the brain stem after transcutaneous vagus nerve stimulation.
Fallgatter, A J; Neuhauser, B; Herrmann, M J; Ehlis, A-C; Wagener, A; Scheuerpflug, P; Reiners, K; Riederer, P
Recently, the vagus nerve has gained particular interest in neuropsychiatry, as neurodegenerative diseases like Alzheimer's and Parkinson's disease are supposed to affect the brainstem nuclei of the vagus nerve early in their course. In addition, electric stimulation of the vagus nerve has therapeutic effects in otherwise therapy-refractory epilepsies and depressions. So far, no method is available to assess vagus nerve function in this context. On this background and based on the established techniques of early acoustic evoked potentials we investigated if a transcutaneous electric stimulation of the sensory auricular branch of the vagus nerve innervating parts of the outer ear is feasible in healthy subjects using this hypothesis-generated approach. We were able to record a clear, reproducible Vagus Sensory Evoked Potential (VSEP) measured as far field potential probably originating in vagus nuclei in the brainstem. Further studies are needed to test the interindividual stability and test-retest reliability of this new method before potential diagnostic and therapeutic applications might be evaluated. PMID:14666414
Intracranial facial nerve reconstruction.
Yammine, F G; Dufour, J J; Mohr, G
Surgery for tumours of the cerebellopontine angle (CPA) or the internal auditory canal (IAC) is sometimes complicated by the severing of the seventh nerve. Many procedures are available for facial reanimation. Among these, primary intracranial VII-VII reanastomosis is considered as the method of choice. This series reviews all the cases of primary intracranial facial nerve reconstruction that we have performed either directly or with the use of a nerve graft interposition. Functional results are analyzed according to the House-Brackmann grading scale. The advantages and benefits of this technique are discussed as compared with other methods of facial reanimation, namely, the hypoglossal-facial anastomosis. PMID:10410348
Spinal root origins and innervations of the suprascapular nerve.
Shin, Chuog; Lee, Seo-Eun; Yu, Kee-Hyun; Chae, Han-Kyo; Lee, Kyu-Seok
The suprascapular nerve branches provide efferent innervation to the supraspinatus and infraspinatus muscles as well as sensory innervation to the shoulder joint. This study was carried out to verify the spinal root origins and innervations of the suprascapular nerve. Fifty samples of the suprascapular nerve taken from 37 adult Korean cadavers were used in this study. The suprascapular nerve was found to comprise the ventral rami of the C5 and C6 in 76.0% of the fifty samples; C4, C5, and C6 nerves in 18.0%; and C5 nerve in only 6.0%. The C5 nerve was consistently shown to be the largest in mean diameter and was found to be a major contributor of nerve fibers leading to the suprascapular nerve. This study shows that the main spinal component of the suprascapular nerve is C5 nerve. In most cases, the rate of the involvement of the C4 and C6 nerves (18.0 and 94.0%, respectively) with the suprascapular nerve was less than that of C5 nerve. C4 and C5 nerves were shown to contribute nerve fibers to the supraspinatus and infraspinatus muscles and to both shoulder joints, whereas C6 nerve displayed variable patterns of innervation. PMID:19937327
Receptive properties of embryonic chick sensory neurons innervating skin.
Koltzenburg, M; Lewin, G R
Receptive properties of embryonic chick sensory neurons innervating skin. J. Neurophysiol. 78: 2560-2568, 1997. We describe a new in vitro skin-nerve preparation from chick embryos that allows detailed study of the functional properties of developing sensory neurons innervating skin. Functionally single sensory afferents were isolated by recording from their axons in microdissected filaments of the cutaneous femoralis medialis nerve, which innervates skin of the thigh. A total of 157 single neurons were characterized from embryos [embryonic days 17-21 (E17-E21), n = 115] and hatchlings up to 3 wk old (n = 42). Neurons were initially classified on the basis of their conduction velocity; those conducting below 1.0 m/s were being classified as C fibers and faster conducting fibers as A fibers. The proportions of A and C fibers encountered in embryonic and hatchling preparations were not very different, indicating that myelination and axon growth proceeds quite slowly over the period studied. Afferent fibers that could subserve nociceptive and nonnociceptive functions were identified in the time period studied. Subpopulations of low-threshold myelinated afferent units exhibited rapidly or slowly adapting discharges to constant force stimuli and could have tactile functions. Many afferent fibers responded to noxious heat and were excited and sensitized by exposure to inflammatory mediators, suggesting that they are nociceptors. The behavior of these units changed in several respects over the period studied. The discharge of C fibers to noxious heat increased with age as did their mechanical thresholds. A substantial population of heat-responsive neurons (34% of the A fibers) present in embryos were not encountered in hatchling chicks. This indicates that substantial changes in the physiological response properties of sensory afferents occur after hatching. We conclude that this new preparation can be used for quantitative assessment of the receptive properties of developing sensory neurons and has considerable potential for the investigation of factors, such as neurotrophins, that specify and influence the functional phenotype of sensory neurons during embryonic development in vivo. PMID:9356405
Spatial imagery relies on a sensory independent, though sensory sensitive, functional organization within the parietal cortex: a fMRI study of angle discrimination in sighted and congenitally blind individuals.
Bonino, Daniela; Ricciardi, Emiliano; Bernardi, Giulio; Sani, Lorenzo; Gentili, Claudio; Vecchi, Tomaso; Pietrini, Pietro
Although vision offers distinctive information to space representation, individuals who lack vision since birth often show perceptual and representational skills comparable to those found in sighted individuals. However, congenitally blind individuals may result in impaired spatial analysis, when engaging in 'visual' spatial features (e.g., perspective or angle representation) or complex spatial mental abilities. In the present study, we measured behavioral and brain responses using functional magnetic resonance imaging in sighted and congenitally blind individuals during spatial imagery based on a modified version of the mental clock task (e.g., angle discrimination) and a simple recognition control condition, as conveyed across distinct sensory modalities: visual (sighted individuals only), tactile and auditory. Blind individuals were significantly less accurate during the auditory task, but comparable-to-sighted during the tactile task. As expected, both groups showed common neural activations in intraparietal and superior parietal regions across visual and non-visual spatial perception and imagery conditions, indicating the more abstract, sensory independent functional organization of these cortical areas, a property that we named supramodality. At the same time, however, comparisons in brain responses and functional connectivity patterns across experimental conditions demonstrated also a functional lateralization, in a way that correlated with the distinct behavioral performance in blind and sighted individuals. Specifically, blind individuals relied more on right parietal regions, mainly in the tactile and less in the auditory spatial processing. In sighted, spatial representation across modalities relied more on left parietal regions. In conclusions, intraparietal and superior parietal regions subserve supramodal spatial representations in sighted and congenitally blind individuals. Differences in their recruitment across non-visual spatial processing in sighted and blind individuals may be related to distinctive behavioral performance and/or mental strategies adopted when they deal with the same spatial representation as conveyed through different sensory modalities. PMID:25575449
Jack, Megan Marie
Diabetic neuropathy is the most common and debilitating complication of diabetes mellitus with over half of all patients developing altered sensation as a result of damage to peripheral sensory neurons. Hyperglycemia results in altered nerve...
Sensory neuropathies including painful and toxic neuropathies
John H. J. Wokke; Gert W. van Dijk
In most peripheral neuropathies, dysfunction of motor and sensory nerve fibres is present. However, in some of them either\\u000a pattern may predominate or be exclusively present. In this review we describe the clinical characteristics of sensory neuropathies,\\u000a with emphasis on their possible causes. Guidelines are given for the diagnostic approach in these patients and, where possible,\\u000a suggestions are given for
Dysfunctional penile cholinergic nerves in diabetic impotent men
Blanco, R.; Saenz de Tejada, I.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A. (Boston Univ. School of Medicine, MA (USA))
Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.
Serotonin unmasks functional NK-2 receptors in vagal sensory neurones of the guinea-pig
Moore, Kimberly A; Taylor, Glen E; Weinreich, Daniel
The regulation of substance P (SP) responsiveness in acutely isolated nodose neurones from adult guinea-pigs was investigated using standard intracellular recording techniques.In control neurones, SP produced no measurable electrophysiological effects. However, following incubation with serotonin (5-HT, 10 ?m), 64% of neurones were depolarized by 10 ± 0.6 mV (n= 84 of 132 neurones) by SP (100 nm). 5-HT-induced SP responses were inhibited by SR48968 (100 nm, n= 6), a neurokinin 2 (NK-2) receptor antagonist, but were unaffected by CP99,994 and SR142801, NK-1 and NK-3 receptor antagonists (n= 3 each), respectively.5-HT-induced unmasking of SP responses was maximal within 5 min. Increasing the 5-HT incubation time up to 120 min did not increase the mean response amplitude or the percentage of SP responsive neurones (P= 0.611 and 0.867, respectively).5-HT-induced unmasking of SP responses was dose dependent (EC50= 14 nm). A 5-HT3 receptor agonist CPBG (1 ?m), mimicked the unmasking effects of 5-HT (n= 10 of 19 neurones), while 5-CT (10 ?m), a non-selective 5-HT agonist devoid of action at 5-HT3 receptors, did not (n= 18). ICS205-930 (1 ?m), a 5-HT3 receptor antagonist, completely blocked the 5-HT-induced unmasking of SP responses (n= 10 of 10 neurones).In 68% of the neurones tested, bath-applied 5-HT (10 ?m) evoked a 178 ± 29.5 nm increase in [Ca2+]i (n= 16), which was blocked by nominally zero [Ca2+]o (n= 4) or by ICS205-930 (1 ?m, n= 4). Nodose neurones incubated with 5-HT in the presence of nominally zero [Ca2+]o did not respond to SP (n= 12 of 13 neurones) in Locke solution containing normal [Ca2+]o, indicating that the 5-HT-mediated elevation of [Ca2+]i is required for unmasking of SP responses. Calmidazolium (100 nm), a calmodulin inhibitor, inhibited the unmasking effects of 5-HT (n= 5 of 5 neurones).Incubating neurones with the nitric oxide (NO) donors papaNONOate (1 mm, 15–30 min) or SNAP (50 ?m, 30–60 min) unmasked depolarizing SP responses in 71% and 45% of the neurones studied, respectively. L-NMMA (30 ?m), a NO synthase inhibitor, blocked 5-HT-induced unmasking of SP responses (n= 10 of 10 neurones).In sum, these results suggest that stimulation of 5-HT3 receptors activates an intracellular signalling cascade that couples calcium-calmodulin and NO activation to NK-2 receptor unmasking in sensory neurones. PMID:9831720
Noninvasive and painless magnetic stimulation of nerves improved brain motor function and mobility in a cerebral palsy case.
Flamand, Véronique H; Schneider, Cyril
Motor deficits in cerebral palsy disturb functional independence. This study tested whether noninvasive and painless repetitive peripheral magnetic stimulation could improve motor function in a 7-year-old boy with spastic hemiparetic cerebral palsy. Stimulation was applied over different nerves of the lower limbs for 5 sessions. We measured the concurrent aftereffects of this intervention on ankle motor control, gait (walking velocity, stride length, cadence, cycle duration), and function of brain motor pathways. We observed a decrease of ankle plantar flexors resistance to stretch, an increase of active dorsiflexion range of movement, and improvements of corticospinal control of ankle dorsiflexors. Joint mobility changes were still present 15 days after the end of stimulation, when all gait parameters were also improved. Resistance to stretch was still lower than prestimulation values 45 days after the end of stimulation. This case illustrates the sustained effects of repetitive peripheral magnetic stimulation on brain plasticity, motor function, and gait. It suggests a potential impact for physical rehabilitation in cerebral palsy. PMID:24907638
MRI-Apparent Localized Deformation of the Median Nerve Within the Carpal Tunnel During Functional Hand Loading
Goetz, Jessica E.; Kunze, Nicole M.; Main, Erin K.; Thedens, Daniel R.; Baer, Thomas E.; Lawler, Ericka A.; Brown, Thomas D.
In MR images, the median nerve of carpal tunnel syndrome (CTS) patients frequently appears flatter than in healthy subjects. The purpose of this work was to develop a metric to quantify localized median nerve deformation rather than global nerve flattening, the hypothesis being that localized median nerve deformation would be elevated in CTS patients. Twelve patients with CTS and 12 matched normals underwent MRI scanning in eight isometrically loaded hand conditions. 2D cross sections of the proximal and distal tunnel were analyzed for nerve cross sectional area, flattening ratio, and a position shift to the dorsal side of the tunnel. Additionally, new metrics based on the angulation of the nerve perimeter in 0.5-mm lengths around the boundary were calculated. The localized deformation metrics were able to detect differences between CTS patients and healthy subjects that could not be appreciated from the flattening ratio. During most hand activities, normal subjects had a higher average percentage of locally deformed nerve boundary than did CTS patients, despite having a rounder overall shape. Less local nerve deformation in the CTS patient group resulting from its interaction with flexor tendons suggests that the nerve may be less compliant in CTS patients. PMID:23612911
The Effects of Irreversible Electroporation (IRE) on Nerves
Wei Li; Qingyu Fan; Zhenwei Ji; Xiuchun Qiu; Zhao Li; Ilya Ulasov
BackgroundIf a critical nerve is circumferentially involved with tumor, radical surgery intended to cure the cancer must sacrifice the nerve. Loss of critical nerves may lead to serious consequences. In spite of the impressive technical advancements in nerve reconstruction, complete recovery and normalization of nerve function is difficult to achieve. Though irreversible electroporation (IRE) might be a promising choice to
Functional Dissection of the Sensory Rays in Caenorhabditis elegans Male Mating Behavior
Koo, Pamela Kristine
.................................................. 13 Screening of A and B neuron ablated animals mating assays .................................................................................. 14 III FUNCTION OF THE RAYS... to readily produce transgenic animals in the lab [6-10]. As the C. elegans body is transparent, it is a relatively simple process to observe expression patterns for any number of genes by driving fluorescent protein expression with the promoter...
Behavioral and Management Problems of Mentally Retarded Functioning Within the Sensori-Motor Stage.
ERIC Educational Resources Information Center
Jedrysek, Eleonora; Soles, Bee
Psychometric test and the Uzgiris-Hunt Scale I (the Development of Visual Pursuit and the Permanence of Objects) were administered to mentally retarded preschoolers (N=105), school aged children (N=35), and adolescents (N=8), all functioning in the sensorimotor stage of development. Performances for each group are reported, and parent reactions…
Functional and structural changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea
Fatouleh, Rania H.; Hammam, Elie; Lundblad, Linda C.; Macey, Paul M.; McKenzie, David K.; Henderson, Luke A.; Macefield, Vaughan G.
Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnoea (OSA) during daytime wakefulness, leading to hypertension, but the underlying mechanisms are poorly understood. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI) of the brain we aimed to identify the central processes responsible for the sympathoexcitation. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted percutaneously into the common peroneal nerve in 17 OSA patients and 15 healthy controls lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. Fluctuations in BOLD signal intensity covaried with the intensity of the concurrently recorded bursts of MSNA. In both groups there was a positive correlation between MSNA and signal intensity in the left and right insulae, dorsolateral prefrontal cortex (dlPFC), dorsal precuneus, sensorimotor cortex and posterior temporal cortex, and the right mid-cingulate cortex and hypothalamus. In OSA the left and right dlPFC, medial PFC (mPFC), dorsal precuneus, anterior cingulate cortex, retrosplenial cortex and caudate nucleus showed augmented signal changes compared with controls, while the right hippocampus/parahippocampus signal intensity decreased in controls but did not change in the OSA subjects. In addition, there were significant increases in grey matter volume in the left mid-insula, the right insula, left and right primary motor cortices, left premotor cortex, left hippocampus and within the brainstem and cerebellum, and significant decreases in the mPFC, occipital lobe, right posterior cingulate cortex, left cerebellar cortex and the left and right amygdala in OSA, but there was no overlap between these structural changes and the functional changes in OSA. These data suggest that the elevated muscle vasoconstrictor drive in OSA may result from functional changes within these brain regions, which are known to be directly or indirectly involved in the modulation of sympathetic outflow via the brainstem. That there was no overlap in the structural and functional changes suggests that asphyxic damage due to repeated episodes of nocturnal obstructive apnoea is not the main cause of the sympathoexcitation. PMID:25379440
White matter changes linked to visual recovery after nerve decompression
Paul, David A.; Gaffin-Cahn, Elon; Hintz, Eric B.; Adeclat, Giscard J.; Zhu, Tong; Williams, Zoë R.; Vates, G. Edward; Mahon, Bradford Z.
The relationship between the integrity of white matter tracts and cortical function in the human brain remains poorly understood. Here we use a model of reversible white matter injury, compression of the optic chiasm by tumors of the pituitary gland, to study the structural and functional changes that attend spontaneous recovery of cortical function and visual abilities after surgical tumor removal and subsequent decompression of the nerves. We show that compression of the optic chiasm leads to demyelination of the optic tracts, which reverses as quickly as 4 weeks after nerve decompression. Furthermore, variability across patients in the severity of demyelination in the optic tracts predicts visual ability and functional activity in early cortical visual areas, and pre-operative measurements of myelination in the optic tracts predicts the magnitude of visual recovery after surgery. These data indicate that rapid regeneration of myelin in the human brain is a significant component of the normalization of cortical activity, and ultimately the recovery of sensory and cognitive function, after nerve decompression. More generally, our findings demonstrate the utility of diffusion tensor imaging as an in vivo measure of myelination in the human brain. PMID:25504884
Systemic Down-Regulation of Delta-9 Desaturase Promotes Muscle Oxidative Metabolism and Accelerates Muscle Function Recovery following Nerve Injury
Henriques, Alexandre; Lequeu, Thiebault; Rene, Frederique; Bindler, Françoise; Dirrig-Grosch, Sylvie; Oudart, Hugues; Palamiuc, Lavinia; Metz-Boutigue, Marie-Helene; Dupuis, Luc; Marchioni, Eric; Gonzalez De Aguilar, Jose-Luis; Loeffler, Jean-Philippe
The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS). Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles. PMID:23785402
Meta analysis of olfactory ensheathing cell transplantation promoting functional recovery of motor nerves in rats with complete spinal cord transection
Liu, Jun; Chen, Ping; Wang, Qi; Chen, Yu; Yu, Haiong; Ma, Junxiong; Guo, Mingming; Piao, Meihui; Ren, Weijian; Xiang, Liangbi
OBJECTIVE: To evaluate the effects of olfactory ensheathing cell transplantation on functional recovery of rats with complete spinal cord transection. DATA SOURCES: A computer-based online search of Medline (1989–2013), Embase (1989–2013), Cochrane library (1989–2013), Chinese Biomedical Literature Database (1989–2013), China National Knowledge Infrastructure (1989–2013), VIP (1989–2013), Wanfang databases (1989–2013) and Chinese Clinical Trial Register was conducted to collect randomized controlled trial data regarding olfactory ensheathing cell transplantation for the treatment of complete spinal cord transection in rats. SELECTION CRITERIA: Randomized controlled trials investigating olfactory ensheathing cell transplantation and other transplantation methods for promoting neurological functional recovery of rats with complete spinal cord transection were included in the analysis. Meta analysis was conducted using RevMan 4.2.2 software. MAIN OUTCOME MEASURES: Basso, Beattie and Bresnahan scores of rats with complete spinal cord transection were evaluated in this study. RESULTS: Six randomized controlled trials with high quality methodology were included. Meta analysis showed that Basso, Beattie and Bresnahan scores were significantly higher in the olfactory ensheathing cell transplantation group compared with the control group (WMD = 3.16, 95% CI (1.68, 4.65); P < 0.00001). CONCLUSION: Experimental studies have shown that olfactory ensheathing cell transplantation can promote the functional recovery of motor nerves in rats with complete spinal cord transection. PMID:25422649
Intrinsic Signal Changes Accompanying Sensory Stimulation: Functional Brain Mapping with Magnetic Resonance Imaging
Seiji Ogawa; David W. Tank; Ravi Menon; Jutta M. Ellermann; Seong-Gi Kim; Hellmut Merkle; Kamil Ugurbil
We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce high-spatial-resolution functional brain maps in humans. Reducing the image-acquisition echo
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Aid in Functional Recovery of Sensory Pathways following Contusive Spinal Cord Injury
All, Angelo H.; Bazley, Faith A.; Gupta, Siddharth; Pashai, Nikta; Hu, Charles; Pourmorteza, Amir; Kerr, Candace
Background Transplantations of human stem cell derivatives have been widely investigated in rodent models for the potential restoration of function of neural pathways after spinal cord injury (SCI). Studies have already demonstrated cells survival following transplantation in SCI. We sought to evaluate survival and potential therapeutic effects of transplanted human embryonic stem (hES) cell-derived oligodendrocyte progenitor cells (OPCs) in a contusive injury in rats. Bioluminescence imaging was utilized to verify survivability of cells up to 4 weeks, and somatosensory evoked potential (SSEPs) were recorded at the cortex to monitor function of sensory pathways throughout the 6-week recovery period. Principal Findings hES cells were transduced with the firefly luciferase gene and differentiated into OPCs. OPCs were transplanted into the lesion epicenter of rat spinal cords 2 hours after inducing a moderate contusive SCI. The hES-treatment group showed improved SSEPs, including increased amplitude and decreased latencies, compared to the control group. The bioluminescence of transplanted OPCs decreased by 97% in the injured spinal cord compared to only 80% when injected into an uninjured spinal cord. Bioluminescence increased in both experimental groups such that by week 3, no statistical difference was detected, signifying that the cells survived and proliferated independent of injury. Post-mortem histology of the spinal cords showed integration of human cells expressing mature oligodendrocyte markers and myelin basic protein without the expression of markers for astrocytes (GFAP) or pluripotent cells (OCT4). Conclusions hES-derived OPCs transplanted 2 hours after contusive SCI survive and differentiate into OLs that produce MBP. Treated rats demonstrated functional improvements in SSEP amplitudes and latencies compared to controls as early as 1 week post-injury. Finally, the hostile injury microenvironment at 2 hours post-injury initially caused increased cell death but did not affect the long-term cell proliferation or survival, indicating that cells can be transplanted sooner than conventionally accepted. PMID:23091637
Cyclophosphamide-Induced Bladder Inflammation Sensitizes and Enhances P2X Receptor Function in Rat Bladder Sensory Neurons
Dang, Khoa; Lamb, Kenneth; Cohen, Michael; Bielefeldt, Klaus; Gebhart, G. F.
We studied sensitization of retrogradely labeled bladder sensory neurons and plasticity of P2X receptor function in a model of cystitis using patch-clamp techniques. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally to rats on days 0, 2, and 4. On day 5, lumbosacral (LS, L6–S2) or thoracolumbar (TL, T12–L2) dorsal root ganglia were removed and dissociated. Bladders from CYP-treated rats showed partial loss of the urothelium and greater myeloperoxidase activity compared with controls. Bladder neurons from CYP-treated rats were increased in size (based on whole cell capacitance) compared with controls and exhibited lower activation threshold, increased action potential width, and greater number of action potentials in response to current injection or application of purinergic agonists. Most control LS bladder neurons (>85%) responded to ATP or ?,?-metATP with a slowly desensitizing current; these agonists affected only half of TL neurons, producing predominantly fast/mixed desensitizing currents. CYP treatment increased the fraction of TL bladder neurons sensitive to purinergic agonists (>80%) and significantly increased current density in both LS and TL bladder neurons compared with control. Importantly, LS and TL neurons from CYP-treated rats showed a selective increase in the functional expression of heteromeric P2X2/3 and homomeric P2X3 receptors, respectively. Although desensitizing kinetics were slower in LS neurons from CYP-treated compared with control rats, recovery kinetics were similar. The present results demonstrate that bladder inflammation sensitizes and increases P2X receptor expression and/or function for both pelvic and lumbar splanchnic pathways, which contribute, in part, to the hypersensitivity associated with cystitis. PMID:17959738
Notch Is Required in Adult Drosophila Sensory Neurons for Morphological and Functional Plasticity of the Olfactory Circuit
Struhl, Gary
Olfactory receptor neurons (ORNs) convey odor information to the central brain, but like other sensory neurons were thought to play a passive role in memory formation and storage. Here we show that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. Specifically, we show that Notch activity in ORNs is necessary for the odor specific increase in the volume of glomeruli that occurs as a consequence of prolonged odor exposure. Calcium imaging experiments indicate that Notch in ORNs is also required for the chronic odor induced changes in the physiology of ORNs and the ensuing changes in the physiological response of their second order projection neurons (PNs). We further show that Notch in ORNs acts by both canonical cleavage-dependent and non-canonical cleavage-independent pathways. The Notch ligand Delta (Dl) in PNs switches the balance between the pathways. These data define a circuit whereby, in conjunction with odor, N activity in the periphery regulates the activity of neurons in the central brain and Dl in the central brain regulates N activity in the periphery. Our work highlights the importance of experience dependent plasticity at the first olfactory synapse. PMID:26011623
Implications of Sensory Stimulation in Self-Destructive Behavior.
ERIC Educational Resources Information Center
Edelson, Stephen M.
The author extends the self stimulatory theory of self destructive behavior in autistic, schizophrenic, and mentally retarded individuals to suggest that damage of the skin's nerve structure lowers the tactile sensory threshold for physical input and enables individuals to obtain sensory stimulation by repeatedly depressing the damaged area. (CL)
Historically, perception has been viewed as a modular function, with the different sensory modalities operating independently of
Shams, Ladan B.
nucleus or the ventrobasal nucleus from their normal sensory input by sectioning the major input pathways bobwhite quail chicks were prenatally exposed to an auditory, visual, tactile or vestibular stimuli
Regenerating sensory neurones of diabetic rats express reduced levels of mRNA for GAP43, ?-preprotachykinin and the nerve growth factor receptors, trkA and p75 NGFR
Kengo Maeda; Paul Fernyhough; David R. Tomlinson
Nerve growth factor (NGF) is considered to play a role in neurite outgrowth of small fibres which express its high-affinity receptor, trkA. Nerve regeneration is delayed in diabetes mellitus following an experimental crush injury. In steady-state (i.e., in the absence of axotomy) diabetic rats also show reduced expression of NGF in certain target tissues. This study was designed to measure
Möbius-strip-like columnar functional connections are revealed in somato-sensory receptive field centroids
Wright, James Joseph; Bourke, Paul David; Favorov, Oleg Vyachesslavovich
Receptive fields of neurons in the forelimb region of areas 3b and 1 of primary somatosensory cortex, in cats and monkeys, were mapped using extracellular recordings obtained sequentially from nearly radial penetrations. Locations of the field centroids indicated the presence of a functional system in which cortical homotypic representations of the limb surfaces are entwined in three-dimensional Möbius-strip-like patterns of synaptic connections. Boundaries of somatosensory receptive field in nested groups irregularly overlie the centroid order, and are interpreted as arising from the superposition of learned connections upon the embryonic order. Since the theory of embryonic synaptic self-organization used to model these results was devised and earlier used to explain findings in primary visual cortex, the present findings suggest the theory may be of general application throughout cortex and may reveal a modular functional synaptic system, which, only in some parts of the cortex, and in some species, is manifest as anatomical ordering into columns. PMID:25400552
Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells
Kunz, Dieter; Walker, Gaby; Bedoucha, Marc; Certa, Ulrich; März-Weiss, Pia; Dimitriades-Schmutz, Beatrice; Otten, Uwe
Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6) and the neurotrophin (NT) Nerve Growth Factor (NGF) for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold), regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold), growth differentiation factor 15 (GDF15; 80-fold), platelet-derived growth factor alpha (PDGFA; 69-fold), growth hormone releasing hormone (GHRH; 30-fold), adenylate cyclase activating polypeptide (PACAP; 20-fold) and hepatocyte growth factor (HGF; 5-fold). NGF recruits GDF15 (131-fold), transforming growth factor beta 1 (TGFB1; 101-fold) and brain-derived neurotrophic factor (BDNF; 89-fold). Both stimuli activate growth-associated protein 43 (GAP-43) indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold) and early growth response 1 (Egr1/Zif268; 3-fold) known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell adhesion, small molecule biochemistry aiming at changing intracellular concentrations of second messengers such as Ca2+ and cAMP as well as expression of enzymes involved in posttranslational modification of proteins. Conclusion The current data provide novel candidate genes involved in neuronal differentiation, notably for the neuropoietic cytokine IL-6. Our findings may also have impact on the clinical treatment of peripheral nerve injury. Local application of a designer cytokine such as H-IL-6 with drastically enhanced bioactivity in combination with NTs may generate a potent reparative microenvironment. PMID:19239705
Reactive Oxygen Species (ROS) and the Sensory Neurovascular Component
Rabea Graepel; Jennifer Victoria Bodkin; Susan Diana Brain
\\u000a A dense perivascular network of C- and A?-sensory nerve fibers innervate the vascular system and are ideally situated to influence\\u000a vascular events. The nerves release potent vasodilator neuropeptides including substances P, CGRP and a range of other agents,\\u000a depending on their location and the nature of nerve activation. A number of interactions between neuropeptides and ROS have\\u000a been described and
Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain
Pain often accompanies cancer and most current therapies for treating cancer pain have significant unwanted side effects. Targeting nerve growth factor (NGF) or its cognate receptor tropomyosin receptor kinase A (TrkA) has become an attractive target for attenuating chronic pain. In the present report, we use a mouse model of bone cancer pain and examine whether oral administration of a selective small molecule Trk inhibitor (ARRY-470, which blocks TrkA, TrkB and TrkC kinase activity at low nm concentrations) has a significant effect on cancer-induced pain behaviors, tumor-induced remodeling of sensory nerve fibers, tumor growth and tumor-induced bone remodeling. Early/sustained (initiated day 6 post cancer cell injection), but not late/acute (initiated day 18 post cancer cell injection) administration of ARRY-470 markedly attenuated bone cancer pain and significantly blocked the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor bearing bone, but did not have a significant effect on tumor growth or bone remodeling. These data suggest that, like therapies that target the cancer itself, the earlier that the blockade of TrkA occurs, the more effective the control of cancer pain and the tumor-induced remodeling of sensory nerve fibers. Developing targeted therapies that relieve cancer pain without the side effects of current analgesics has the potential to significantly improve the quality of life and functional status of cancer patients. PMID:21138586
Evaluation of functional properties of composite flours and sensorial attributes of composite flour biscuits.
Chandra, Suresh; Singh, Samsher; Kumari, Durvesh
The present study was undertaken to develop biscuits from the composite flours. Composite flours were prepared by blending wheat flour with rice flour, green gram flour and potato flour in ratios of 100:0:0:0 (W100), 85:5:5:5 (W85), 70:10:10:10 (W70) and 55:15:15:15 (W55), respectively. The functional properties of composite flours such as swelling capacity, water absorption capacity, oil absorption capacity, emulsion activity, emulsion stability, foam capacity, foam stability, gelatinization temperature, least gelation concentration and bulk density were increased with increase in the incorporation of other flours with wheat flour. Overall acceptability for composite flour biscuits was awarded highest score for W55 followed by W70 and W85 as compared to control biscuits. All biscuits coincided in the range of 'like moderately' to 'like very much' for composite flours biscuits while 'like slightly' to like moderately' for control biscuits. PMID:26028751
Mechanical stimulation increases intracellular calcium concentration in nodose sensory neurons
R. V. Sharma; M. W. Chapleau; G. Hajduczok; R. E. Wachtel; L. J. Waite; R. C. Bhalla; F. M. Abboud
The cellular mechanisms involved in activation of mechanosensitive visceral sensory nerves are poorly understood. The major goal of this study was to determine the effect of mechanical stimulation on intracellular calcium concentration ([Ca2+]i) using nodose sensory neurons grown in culture. Primary cultures of nodose sensory neurons were prepared by enzymatic dispersion from nodose ganglia of 4–8 week old Sprague-Dawley rats.
The consistent presence of the human accessory deep peroneal nerve.
Kudoh, H; Sakai, T; Horiguchi, M
Twenty-four human legs were dissected macroscopically to study the morphological details of the accessory deep peroneal nerve. This nerve arose from the superficial peroneal nerve and descended in the lateral compartment of the leg, deep to peroneus longus along the posterior border of peroneus brevis. Approaching the ankle joint, this nerve passed through the peroneal tunnels to wind around the lateral malleolus; it then crossed beneath the peroneus brevis tendon anteriorly to reach the dorsum of the foot. The accessory deep peroneal nerve was found in every case examined and constantly gave off muscular branches to peroneus brevis and sensory branches to the ankle region. In addition, this nerve occasionally had muscular branches to peroneus longus and extensor digitorum brevis, and sensory branches to the fibula and the foot. The anomalous muscles around the lateral malleolus were also innervated by this nerve. Neither cutaneous branches nor communicating branches with other nerves were found. The present study reveals that the accessory deep peroneal nerve is consistently present and possesses a proper motor and sensory distribution in the lateral region of the leg and ankle. It is not an anomalous nerve as has previously been suggested. PMID:10227671
Unilateral nerve injury produces bilateral loss of distal innervation.
Oaklander, Anne Louise; Brown, Jennifer M
There are no known anatomical connections between neurons that innervate homologous right and left body parts. Nevertheless, some patients develop bilateral abnormalities after unilateral injury, a phenomenon often unrecognized and not yet characterized. Therefore, we examined in rats the effects of ligating and cutting one tibial nerve on sensory function and on density of innervation in hind paws contralaterally as well as ipsilaterally to the injury, at times between 1 day and 5 months after surgery. Punches removed from tibial- or sural-innervated planter paw skin were immunolabeled to quantitate epidermal nerve endings. Naive and sham-operated rats provided controls. Axotomized rats had near-total loss of PGP9.5(+) innervation within ipsilateral tibial-innervated skin at all time-points. Adjacent ipsilateral sural-innervated skin had persistent hyperalgesia without denervation, and robust axonal sprouting at 5 months after surgery. Contralesional hind paws lost 54% of innervation in tibial-innervated epidermis starting 1 week after surgery and persisting throughout. Contralesional sural-innervated skin had neither neurite loss nor sprouting. These results imply that unilateral nerve injury can cause profound, long lasting, nerve-branch-specific loss of distal innervation contralaterally as well as ipsilaterally. They discredit the practice of using tissues contralateral to an injury to provide normative controls and suggest the possibility of rapid, transmedian postinjury signals between homologous mirror-image neurons. PMID:15122703
The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects.
Johnson, M I; Hajela, V K; Ashton, C H; Thompson, J W
The present study examines the effects of auricular transcutaneous electrical nerve stimulation (TENS) on electrical pain threshold measured at the ipsilateral wrist and autonomic functions including skin temperature, blood pressure and pulse rate in 24 healthy subjects. TENS was administered as low frequency trains of pulses delivered at a 'strong but comfortable' intensity to 1 of 3 auricular points to be examined: (i) autonomic effects (autonomic point), (ii) pain threshold effects (wrist point), and (iii) placebo effects at an unrelated point (face point). A fourth untreated group was designated as a situation control. The main finding of the study was that auricular TENS produced no significant overall effects on experimental pain threshold or autonomic functions recorded under the present conditions. However, pain threshold was found to increase by over 50% of its pretreatment baseline in 4 subjects and by 30% in 6 subjects. This rise was not dependent upon the site of auricular TENS. The possible mechanisms of such changes are discussed. PMID:1758713
Disorders of the lower cranial nerves
Finsterer, Josef; Grisold, Wolfgang
Lesions of the lower cranial nerves (LCN) are due to numerous causes, which need to be differentiated to optimize management and outcome. This review aims at summarizing and discussing diseases affecting LCN. Review of publications dealing with disorders of the LCN in humans. Affection of multiple LCN is much more frequent than the affection of a single LCN. LCN may be affected solely or together with more proximal cranial nerves, with central nervous system disease, or with nonneurological disorders. LCN lesions have to be suspected if there are typical symptoms or signs attributable to a LCN. Causes of LCN lesions can be classified as genetic, vascular, traumatic, iatrogenic, infectious, immunologic, metabolic, nutritional, degenerative, or neoplastic. Treatment of LCN lesions depends on the underlying cause. An effective treatment is available in the majority of the cases, but a prerequisite for complete recovery is the prompt and correct diagnosis. LCN lesions need to be considered in case of disturbed speech, swallowing, coughing, deglutition, sensory functions, taste, or autonomic functions, neuralgic pain, dysphagia, head, pharyngeal, or neck pain, cardiac or gastrointestinal compromise, or weakness of the trapezius, sternocleidomastoid, or the tongue muscles. To correctly assess manifestations of LCN lesions, precise knowledge of the anatomy and physiology of the area is required.
Synthetic Self-Assembling Clostridial Chimera for Modulation of Sensory Fu