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Latest Evidence-Based Application for Radiofrequency Neurotomy (LEARN): Best Practice Guidelines from the American Society of Pain and Neuroscience (ASPN)

Abstract Radiofrequency neurotomy (RFN), also known as radiofrequency ablation (RFA), is a common interventional procedure used to treat pain from an innervated structure. RFN has historically been used to treat chronic facet-joint mediated pain. The use of RFN has more recently expanded beyond facet-joint mediated pain to peripherally innervated targets. In addition, there has also been the emergence of different radiofrequency modalities, including pulsed and cooled RFN. The use of RFN has been particularly important where conservative and/or surgical measures have failed to provide pain relief. With the emergence of this therapeutic option and its novel applications, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidance. The authors formed a multidisciplinary work group tasked to examine the latest evidence-based medicine for the various applications of RFN, including cervical, thoracic, lumbar spine; posterior sacroiliac joint pain; hip and knee joints; and occipital neuralgia. Best practice guidelines, evidence and consensus grading were provided for each anatomical target.


Introduction
Radiofrequency neurotomy (RFN), also known as radiofrequency ablation (RFA), is a standard procedure performed to treat pain from an innervated structure. Increased utilization of RFN has been driven by an aging population, a desire to avoid more invasive procedures, and the desire for an alternative to less efficacious and higher risk options, such as chronic long-term opioid therapy. Historically, RFN has been used to treat chronic facet-joint mediated pain diagnosed by facet or medial branch blocks. With the expanded use of this therapy for novel applications involving peripheral joints and nerves, there was an identified need for evidencebased best practice guidance. In addition, there has also been the emergence of different radiofrequency modalities, including pulsed and cooled RFN. This review aims to present the most up-to-date use of radiofrequency neurotomy based on anatomical targets.

History of Radiofrequency Neurotomy
In the early 1930s, Kirschner demonstrated the first known utilization of RFN with thermocoagulation of the Gasserian ganglion for trigeminal neuralgia. Kirschner's initial work demonstrated that continuous radiofrequency (CRF) current created a focal thermal lesion in a neural pathway with the goal to interrupt nociception. 1 Two decades later, in the 1950s, work by Aronow and Cosman would lead to the advent of the first commercially available radiofrequency (RF) systems. Shealy and Bogduk would later refine percutaneous medial branch RF neurotomy techniques, 2 a procedure that essentially replaced surgical neurotomy. Initially, limitations in technology only allowed for the treatment of cervical and lumbar facet disease. However, CRF has now been studied in the treatment of numerous pain pathologies. Despite the technological advances, the risk of motor deficit remains aconcern. [3][4][5][6] Pulsed radiofrequency (PRF) technology, first introduced in Austria in 1995, was developed to reduce the risk of motor deficit as it does not create a destructive thermal lesion. Ayrapetyan proposed that PRF efficacy may be secondary to magnetic field exposure as opposed to thermal coagulation. 7 In 1998, the first article on the effects of PRF on the dorsal root ganglion was published. [8][9][10] A recent novel modality for ablation of neural pathways is cooled radiofrequency (CRFN) thermal neurotomy. Despite the name, this technique allows for a larger thermal lesion to be formed than traditional RFN ( Figure 1). This method has been increasingly utilized for the interruption of nociceptive pathways after its initial use in cardiac electrophysiology and tumor ablation. Since 2010, there has been emerging evidence supporting the use of CRFN for chronic knee, hip and back pain. [11][12][13] Methods Based on the identified gap in guidance on the use of RFN, the American Society of Pain and Neuroscience (ASPN) formed a multidisciplinary work group of pain medicine specialists to create a best practice guideline. Selection of panel members was based on expertise, publications, research, clinical experience, practice setting and diversity. All work group members actively utilize RFN in their respective practices. While there have been previous publications on the use of RFN, work group members identified the need to expand best practice guidelines to address sacroiliac joint pain and peripheral joint disease. The aim of the paper was to present the most up-to-date use of this modality based on anatomical targets.
A formal literature search was performed by the authors with clinical experience in RFN procedures. Database searches of Embase, PubMed and Medline, utilizing the following keywords was performed: cervical radiofrequency neurotomy/ablation, thoracic radiofrequency neurotomy/ablation, lumbar radiofrequency neurotomy/ablation, sacroiliac joint radiofrequency neurotomy/ablation, lateral sacral branch neurotomy/ablation, hip radiofrequency neurotomy/ablation, genicular radiofrequency neurotomy/ablation, knee radiofrequency neurotomy/ablation, and occipital radiofrequency neurotomy/ablation. The terms neurotomy and ablation are used interchangeably in this paper. In addition, the terms facet, medial branch, and medial branch nerves are used interchangeably in this paper.
Inclusion criteria for literature search were randomized controlled trials, prospective and retrospective observational studies. Exclusion criteria included conference proceedings, expert opinions, and unpublished data. The records were filtered for "pain management" specific topics. The remaining abstracts were reviewed by two authors utilizing PICOS technique with comparison to other treatment (active, sham or placebo) or no treatment, and outcome measures to include improvement in pain by any scale. Secondary outcomes of interest: function, analgesic use, subsequent need for surgery, healthcare utilization, return to work. The screened manuscripts were then separated by anatomic targets: A formal meta-analysis was not conducted due to heterogeneity in study types, diagnostic criteria, variances in interventional techniques utilized and discrepancies in primary and secondary endpoints. Literature review was conducted by each work group member for assessment of both quality of evidence and grade of recommendation. Any discrepancies in grading were brought to the work group for discussion so that a consensus could be reached. In the end, there were no discrepancies to disclose. Each section includes a summary of: 1. The most current evidence-based medicine for the use of RFN 2. Patient selection guidance 3. Procedure techniques and best practice recommendations 4. Treatment and research gaps. 5. Quality of evidence for each anatomic target graded from I-III as detailed in Table 1. 6. Consensus statement and expert opinion analysis were rendered using the US Preventive Services Task Force (USPSTF) grading scale ( Table 2). The Task Force assigns to each of its recommendations  a letter grade (A, B, C, or D) or issues an "I" statement, based on the certainty of the evidence and on the balance of benefits and harms of the preventive service. The USPSTF updated its definitions of the grades it assigns to recommendations and now includes "suggestions for practice" associated with each grade.
Conflict of Interest Management: Each member of the panel recused itself from any decision in which a conflict existed. One author (KA) had the responsibility of evaluating the paper for bias and resolving any potential issues prior to manuscript publication.

Cervical Medial Branch Radiofrequency Neurotomy
Cervical medial branch RFN, also commonly referred to as cervical facet joint neurotomy or ablation, is used for the treatment of chronic neck pain and cervicogenic headache. 14 While physical examination and imaging may support the diagnosis of cervical facet-mediated pain, these alone have not been validated as standalone diagnostic techniques. Neck tenderness or pain with extension and/or rotational movements, though often associated with cervical facet joint mediated pain, are not specific to solely facet-mediated pain. 15 While commonly used diagnostically in pain medicine, diagnostic cervical medial branch/facet blocks are not specifically covered in this manuscript as they are beyond the scope of this paper. 16

Current Available Evidence of Cervical Medial Branch Radiofrequency Neurotomy
Early descriptive studies of radiofrequency neurotomy date back half a century; recent studies are summarized in Table 3.

Procedure Techniques
The effectiveness of the cervical RFN is highly dependent on proper technique. 24 There is robust evidence for shortand long-term pain relief with denervation protocols involving multiple lesions. 25 This technique has since been adopted as the standard of care. 24

Grade Definition Suggestions for Practice
A The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
Offer or provide this service.

B
The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
Offer or provide this service.

C
The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.
Offer or provide this service for selected patients depending on individual circumstances.

D
The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
Discourage the use of this service.

I
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.  In its most rigorous adoption, cervical medial branch RFN is a two-step procedure: (1) oblique insertion and (2) sagittal insertion, which allows for lesions at two separate sites along the trajectory increasing the area of the thermal lesion. The oblique pass is intended to place lesions over the anterior third of the superior articular process. The sagittal pass is intended to place lesions along the lateral aspect of the articular pillar in which the medial branch nerve is located ( Figure 2).

Best Practices Summary
• Use of cervical RFN is primarily for symptoms of axial neck pain in the absence of radicular symptoms. • Prior to RF of the cervical spine, other possible etiologies should be ruled out. The use of magnetic resonance imaging (MRI) and/or computerized tomography (CT) imaging is highly recommended, but x-rays can also very useful. Although imaging can characterize degenerative changes, it is not a diagnostic for facet-mediated pain. Additionally, discogenic changes do not necessarily rule out the use of RFN. • Physical examination and radiographic findings have no direct diagnostic or prognostic value in determining success of radiofrequency procedures. • The efficacy of RFN is directly related to the rigor of diagnostic blocks performed as well as the use of proper technique for both diagnostic and neurotomy procedures. • Evidence best supports the use of conventional thermal (60-80 degree centigrade) radiofrequency for 60-90 seconds. While the use of pulsed RF on the cervical medial branches has been reported, further studies are necessary. • Multiple passes, and utilizing two separate approaches, may allow for neurotomy in a larger portion of the medial branch, resulting in improved pain relief with longer duration. • If neck pain recurs, evidence supports the use of repeat neurotomy with reproducible efficacy. Although timing is highly variable, the procedure may be repeated as early as every six months. 26

Treatment Gaps & Future Research
Research and evidence gaps exist for cervical medial branch pulsed radiofrequency (PRF). PRF allows for the application of radiofrequency current at lower temperatures, minimizing the damage to surrounding tissue, nerves and/or vasculature. Further research on PRF is required to determine both the efficacy and the safety of this treatment modality, and how it compares to conventional RF.
Although several studies have demonstrated the efficacy of both continuous and pulsed RF within the range of 6 to 12 months, more evidence is clearly needed.

Consensus Statement
Cervical medial branch radiofrequency neurotomy may be used for the treatment of axial neck pain when facet joints have been identified as the etiology of pain via diagnostic blocks. GRADE I A.

Thoracic Medial Branch Radiofrequency Neurotomy
Thoracic medial branch RFN is used for the treatment of chronic thoracic/midback pain. 27 Since physical exam and radiographic techniques are variable and difficult to interpret in these instances, diagnosis of thoracic facet joint pain relies mainly on diagnostic injections. In those cases of positive diagnostic medial branch blocks, the patient may find long-term relief with thoracic RFN.

Current Available Evidence of Thoracic Medial Branch Radiofrequency Neurotomy
The literature surrounding the use of thoracic medial branch RFN is relatively scarce when compared to other levels of the spine. Interestingly, multiple modalities of RFN have been studied in the thoracic spine, albeit with low level of evidence. The published literature is summarized in Table 4.

Procedure Techniques
As with all ablation techniques, the effectiveness of the therapy is highly dependent on proper technique and appropriate lesioning of the thoracic medial branch nerves. Using either an anteroposterior (AP) or ipsilateral oblique fluoroscopic image, the radiofrequency cannula is directed in a caudal-to-cephalad direction and advanced towards the superolateral edge of the targeted thoracic transverse process. This is the site of the thoracic medial branch as it courses along the transverse process ( Figure 3). The ablation is performed per standard protocol based on ablation modality.

Best Practices Summary
• The use of thoracic RFN is indicated for axial midback pain in the absence of radicular symptoms.

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• Low-level evidence suggests that traditional RFA and bipolar RFA may provide longer lasting pain relief than pulsed RFA and CRFA, but given the study's methodological differences, it is impossible to draw any firm conclusions. • Given the location and anatomic variability of thoracic medial branches, patients should be counseled about the risk of pneumothorax. Physicians should have a sound understanding of thoracic fluoroscopic anatomy prior to performing thoracic RFN. • If thoracic pain recurs, evidence suggests that repeat RFN is effective. In the only RCT involving thoracic spine RFN, alcohol ablation was shown to be more efficacious than traditional RFA.

Treatment Gaps & Future Research
Overall, there is a paucity of quality research and publications addressing thoracic medial branch RFN. Thoracic facetrelated back pain would benefit from high-quality research addressing basic questions, including comparison of different RFN modalities to conventional medical management and to each other in a prospective, long-term manner.

Consensus Statement
Thoracic medial branch radiofrequency neurotomy may be used for the treatment of thoracic/midback pain when facet joints have been identified as the etiology of pain via diagnostic blocks. GRADE II-3 C.

Lumbar Medial Branch Radiofrequency Neurotomy
Lumbar radiofrequency neurotomy (LRFN) is the second most common procedure performed in interventional pain practices in the United States. 32 This procedure is also commonly referred to as lumbar medial branch nerve RFN. There has been a 130.6% increase in its utilization from 2007 to 2016. 33,34 Low back pain (LBP) due to lumbar facet joint disease is often treated with LRFN. This diagnosis is prevalent in approximately 45% of lower back pain patients. [35][36][37][38] While LRFN is one of the best studied interventional pain procedures, it is also one of the most debated procedures with constantly evolving evidence. 39,40

Current Available Evidence of Lumbar Medial Branch Radiofrequency Neurotomy
Diagnosing lumbar facet pain is challenging due to its heterogeneous etiology, variable clinical findings, radiographic and clinical course, and the multifactorial nature of low back pain. 39,40 Patients generally complain of axial low back pain with or without radiation into the groin, buttocks, and/or thighs. Axial pain may worsen with extension, lateral bending, rotation, sitting, standing, walking or coughing. 41 Consistent with other arthritic pain, this pain is often worsened by immobility. However, the published evidence does not find these symptoms to correlate well with the success of LRFN. 42 Physical examination findings also have similarly mixed outcomes in the literature. The most studied and utilized physical examination techniques, including "facet loading" or paravertebral tenderness, have minimal ability to reliably predict the efficacy of LRFN. 43 Hence, the literature illustrates that there are no pathognomonic signs with both clinical history and physical examination to reliably diagnose patients with facet-mediated pain or predict the success of LRFN. [43][44][45] Moreover, both MRI and CT scans have no specific findings that help diagnose lumbar facet mediated pathology as the exclusive source of pain. 46,47 As such, the present standard in the diagnosis of lumbar facet mediated pain is diagnostic facet blocks, including both the use of intra-articular facet joint injections and medial branch nerve blocks. 43 Medial branch blocks are considered more predictive for lumbar medial branch RFN success than intra-articular facet injections; however, both techniques have shown better predictive value compared to sham. 47 The optimal volume of anesthetic injectate for diagnostic medial branch blocks recommended is <0.5 cc in order to improve specificity and reduce the risk of spreading to adjacent nerves or structures.
LRFN has been studied extensively with consensus guidelines indicating moderate to strong evidence. [43][44][45] The efficacy of the lumbar medial branch RFN has been described in observational and RCT. Out of the six RCTs, three contained technical flaws in both patient selection and procedural technique, which yielded less reliable and therefore, non-generalizable findings. [54][55][56] Of the literature that is published with acceptable methodology and generalizability, patient benefit from lumbar medial branch RFN is well documented. Table 5 summarizes LRFN studies.

Procedure Techniques
Successful treatment of lumbar facet pain by RFN is contingent on nerve coagulation by heat. 60 The lumbar facet joints are paired, with each joint innervated by the medial branches from the dorsal rami of the same level, as well as the level above. Bogduk et al demonstrated the target for lumbar neurotomy to be the medial branches of the lumbar dorsal rami in their landmark study. 61 In order to target these nerves appropriately, RF needles are placed along the posterior elements of the lumbar vertebral column, at the junction of the superior articular and the transverse processes of the vertebrae. 61 At the L5 level, the dorsal ramus itself is amenable to neurotomy, which runs at the junction of the S1 superior articular process and the sacral ala.
The optimal electrode positioning has now been demonstrated to be parallel to the target nerves after the initial thought process that a perpendicular needle placement may be sufficient [61][62][63] (Figure 4). While the studies varied in their design, the consensus was that the parallel placement of traditional electrodes is indeed the optimal approach for LRFN. 33,42,47 Motor and sensory testing is often suggested prior to RFN, in order to confirm appropriate and safe placement of the electrode tip. As such, injury to the ventral ramus or any other unintended structures may be avoided. This is a topic that has been widely studied and debated. 64 There have been case studies with nerve root injury where motor stimulation was not performed. 65 Given the limited data, even society guidelines are mixed on utilizing sensory and motor stimulation prior to lumbar medial branch RFN. 47 Finally, a recent expert consensus statement recommended sensory stimulation with single-level lesions, with low level of certainty and inconclusive evidence with multiple lesions. Motor stimulation is recommended for both safety and effectiveness purposes. 33 Best Practices Summary • Use of lumbar radiofrequency neurotomy (LRFN) is primarily for symptoms of low back pain in the absence of radicular symptoms. • Prior to LRFN, other possible etiologies by way of either MRI or CT imaging should be ruled out, although imaging is not itself a diagnostic for facetmediated pain. Discogenic changes do not necessarily rule-out the use of LRFN. • Medial branch blocks are generally considered more predictive for success with LRFN than intra-articular facet injections.
• In addition to the success of the initial LRFN, the efficacy of repeat LRFN with pain recurrence has been shown to be highly reproducible. • Optimal electrode positioning is parallel to the target nerves, although more evidence is necessary. • Motor and sensory testing is recommended prior to LRFN, in order to confirm appropriate placement of the electrode tip and to avoid lesioning of any other unintended structures including the ventral ramus. • Evidence best supports the use of conventional thermal (60-80 degree centigrade) radiofrequency for 60-90 seconds. While the use of pulsed RF on the lumbar medial branches has been reported, further studies are necessary.

Treatment Gaps & Future Research
Similar to the cervical region, pulsed radiofrequency (PRF) for the lumbar spine is not covered extensively in the literature. Further research in various forms of RF is needed to determine the efficacy and safety of these treatment modalities. Furthermore, additional research is clearly needed to confirm if a parallel needle placement is indeed the most optimal option, particularly in light of other modalities, such as cooled RF.

Consensus Statement
Lumbar medial branch radiofrequency neurotomy may be used for the treatment of axial low back pain when facet

Lateral Sacral Branch Radiofrequency Neurotomy
Early studies brought attention to the sacroiliac joint as a pain generator through reproduction of symptoms by way of provocative maneuvers and diagnostic/therapeutic injections into the sacroiliac joint (SIJ). 66 Laslett et al found provocative maneuvers to be helpful but lacked sensitivity. 66 There is no evidence to support any provocative SIJ maneuver as pathognomonic for SIJ pain; hence, the use of diagnostic SIJ blocks utilizing local anesthetics with or without steroids has evolved as the current standard. 67 Although, initially, such injections were done blindly, image-guidance has substantially improved the accuracy of this procedure. However, therapeutic intra-articular injections only provide temporary relief for most patients. Recalcitrant cases led to the advent of other treatment options for SIJ dysfunction. RFN emerged as the most viable choice given its known evidence and effectiveness in treating facet-mediated pain. 68 Histological analysis of the sacroiliac joint has verified the presence of nerve fibers within the joint capsule and adjoining ligaments. 69 The sacroiliac joint is thought to receive its innervation from the ventral rami of L4 and L5, the dorsal rami of L5, S1, S2, and S3, as well as the superior gluteal nerve. 70,71 There is an additional ventral innervation of the sacroiliac joint that is inaccessible for denervation.
Sacral lateral branch neurotomy addresses the posterior sacroiliac structures, which includes both the posterior joint and ligaments. Therefore, the response to intraarticular sacroiliac joint injections, per se, does not necessarily correlate to radiofrequency success. 72 However, blocking the innervation lateral to the foramen at different depths has been shown to be more effective. However, there are no placebo-controlled trials for lateral sacral nerve blocks to confirm this thought process. 72 This is a treatment gap in appropriately selecting patients for sacral lateral branch neurotomy.

Current Available Evidence of Lateral Sacral Branch Radiofrequency Neurotomy
Two controlled and two pragmatic RFN studies of the lateral sacral branch are described in Table 6 with the remaining lateral sacral branch radiofrequency neurotomy studies being observational.

Procedure Techniques
The variability in the position of the posterior lateral sacral branches makes diagnostic blocks a technical challenge. As such, monopolar lesions may not necessarily reliably capture the nerve, which has led to the advent of cooled or bipolar RF lesion strategies. There are various studies comparing different forms of RFN of the SIJ; however, results are inconsistent and the study designs have variable patient selection lending to discrepancies in neurotomy techniques used. 73,80 For this reason, monopolar lesions continue to be used as a treatment option; however, multiple lesions along the suspected trajectory of the lateral branches are recommended.
Roberts et al conducted one of the most comprehensive cadaveric anatomical studies to date on the anatomic location of the lateral sacral branches. 90 The lateral branches were dissected out, and radiopaque wires were directly sutured to them. Anterior-posterior fluoroscopic imaging through the S1 superior endplate was obtained. Lesions by 17 versions of seven current sacroiliac joint RF techniques were mapped on fluoroscopic images. The techniques are meticulously described within this manuscript and were compared for: 1) Percentage of lateral branches captured 2) Percentage of SIJ specimens in which 100% of lateral branches were captured 3) Percentage of lateral branches that would not be captured at each level.
The results demonstrated that bipolar techniques captured a greater percentage of the lateral branches than traditionally used monopolar techniques. Furthermore, monopolar capture rates ranged from 49.6% to 64.6%, likely due to the small lesion size created by this technique.
Regarding the locations of the actual thermal lesion, it was found that the use of the palisade technique ( Figure 5) was the most optimal in capturing the lateral branches. The

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peri-foraminal technique ( Figure 6) was found to be an adequate alternative but requires multiple lesions surrounded in the lateral aspect of the S1, S2, S3 neural foramina.

Best Practices Summary
• Diagnosing SIJ pain consists of a physical examination including multiple provocative maneuvers (distraction, side thigh thrust, Gaenslen, compression and sacral thrust). The best predictive power is found with positive provocation utilizing 2 of 4 selected tests. If none of the six provocation tests reproduce pain symptoms, SIJ pathology may be ruled-out. Ober's and Patrick's tests are secondary options, though these have not been extensively studied. • Prior to RF of the lateral sacral nerves, other possible etiologies must be ruled out by way of imaging. Radiographs may show degenerative changes and inflammation within the SIJ but are not diagnostic for SIJ pain.  • Contraindications for RFN include sacral fracture, tumor, radiculopathy, infection and coagulopathy. • A diagnostic block for the lateral sacral branches is highly recommended prior to performing RF, even in cases when previous sacroiliac joint injection was performed. While limited evidence exists regarding diagnostic cutoff, recommendation is for 50% or greater reduction in pain prior to advancing to RF. Multisite and multi-depth technique is recommended to appropriately select RF candidates.
• The use of bipolar or cooled RFN is ideal to ensure that the lateral branches are captured with a larger sized lesion. Using a lateral x-ray view, place six (6) cannuale starting superior to S1 and stopping inferior to S3. Cannulae should be parallel to each other, spaced 10-12 mm from the next and perpendicular to the sacral surface. • The use of monopolar RFN has been shown to be effective clinically, but multiple RF cannula passes or the use of periforaminal technique is recommended to create larger sized lesions. • When using bipolar or monopolar RFN, temperature of 80 degrees Centigrade for 60-90 seconds per cycle is recommended. • The use of a large strip lesion is able to capture most of the lateral branches with a more medial placement of the RF probe.

Treatment Gaps & Future Research
The main limitation found within the literature is the heterogeneity of the studies involved. Most studies utilized intra-articular joint injections to select patients for sacral lateral branch RFN. As identified by Dreyfuss et al, the use of diagnostic nerve blocks in the posterior sacral nerve supply is more appropriate and prognostic for outcomes of RF. Not only is further research needed for the use of diagnostic sacral nerve blocks but also with neurotomy itself. Studies used conventional RF, pulsed RF, and cooled RF, with variable parameters and procedural times. The present literature suggests the clinical efficacy of unipolar, bipolar, cooled and pulsed RF; however, studies are limited and are of fair quality at best.

Consensus Statement
Lateral sacral branch radiofrequency neurotomy may be used for the treatment of posterior sacral ligament and joint pain following positive response to appropriately placed diagnostic blocks. GRADE II-1 B.

Radiofrequency Neurotomy for Peripheral Joints
Large joint RFN has been used predominantly to treat patients with end-stage osteoarthritis (OA). It is estimated that as many as 32 million Americans are affected by OA. 91,92 Large joint RFN has been described for the treatment of hip pain, knee pain, and more recently, the  shoulder pain. As the availability of RFN has evolved, so to have the applications. RFN can also be utilized for treating rheumatologic joint disease, post-arthroplasty pain, metastatic disease, osteonecrosis, and chronic infection. 93 The capsular and intra-articular innervation of large joints is complex. The afferent nerves often originate from multiple motor-sensory nerves, and there are variances in its procedural execution. Due to this complexity, it is imperative that the treating physician understands the regional anatomy of the target area in order to avoid complications.

Current Available Evidence of Knee Joint Radiofrequency Neurotomy
A multitude of studies, including randomized clinical trials (RCT) and meta-analyses, have examined the effectiveness of radiofrequency neurotomy of the knee (Table 7).

Procedure Techniques
Recent meticulous dissection studies, including those by both Tran et al and Fonkoue et al, have revealed evidence for both the use of classical and alternate targets for knee RFN. [115][116][117][118][119][120] Tran et al, in two different cadaver studies demonstrated that the articular branches to the knee terminated in their respective quadrants with minimal overlap, though each quadrant could have multiple contributing nerves in addition to the classic superolateral (SL), superomedial (SM), and inferomedial (IM) genicular nerves. 116 In a 2020 study, the authors used ultrasound-guided RF cannulae to target the classic SL, SM, and IM nerves and then dissected around the cannulae creating a threedimensional digitized model showing that classical landmarking can be effective for genicular RFN, though may not capture all the articular innervating branches of the knee. 117 In 2019 and 2020, Fonkoue et al used dye and subsequent dissection in 21 and 14 cadavers, respectively, to identify the most effective landmark positions for fluoroscopy-guided genicular nerve blockade and RFN. The results demonstrated the increased effectiveness of revised targets that are, in general, more posterior in the knee than the classical landmarks. [118][119][120] Traditionally, fluoroscopy has been used to guide needle placement for RFN, predominantly targeting the genicular nerves as their course along the periosteum (Figure 7). However, more recently ultrasound (US) has been shown to be an effective method of image guidance for RF knee procedures. A systematic review and meta-analysis on US compared knee RFN to sham or other treatments such as steroid injections. One study examined intraarticular pulsed RF. This review concluded that there was significant pain reduction and improvement in function as measured time points from 3 to 12 months. Efficacy of diagnostic blocks was questionable.
Limitations to this review included considerable variation in the RF targets, technique, as well as selection criteria.  121 Three of the studies were RCTs and the remaining studies were prospective studies. Meta-analysis revealed US-guided RF knee procedures to result in a pooled mean difference in pain score of −4.2 (NRS scale) and a 23.2 improvement in WOMAC score compared to baseline before RF. An RCT by Sari et al directly compared USguided RF to fluoroscopic-guided RF, finding similar outcomes between the two modalities. 122 Subgroup analysis found RFN of the genicular nerves as examined by four studies resulted in even greater pain reduction of a mean difference of −4.9 (compared to intra-articular modalities such as pulsed-RF). Adverse events reported were infrequent, mild and transient. Overall, US was found to be an effective, safe, non-ionizing, and technically achievable method for RF procedures of the knee, and that the genicular nerves are the preferred targets.

Best Practice Summary
• Radiofrequency ablative technologies for the nociceptive sensory innervation of the knee have been shown to be an effective therapy for chronic knee pain due to conditions, such as osteoarthritis and post-surgical pain. • Utilization of RFN on the knee obviates a comprehensive knowledge and understanding of the anatomical innervation of the knee, experience with fluoroscopy or ultrasound, and knowledge regarding the principles surrounding RFN. • Evidence-based parameters for electrode settings are the use of 70-80°C for 90-180 seconds. • In terms of technique, targeted genicular nerves for conventional and cooled RFN include the SM, SL, and IM nerves. Due to the variable anatomy of these branches, larger lesion sizes increase the likelihood of success. • Pre-ablative diagnostic blocks with a low volume anesthetic may enable more accurate prognostication of the analgesic response to RFN. • Avoiding unnecessary injury or inadvertent neurotomy of motor nerves, non-targeted sensory nerves, blood vessels, and other non-targeted anatomic structures is essential. Motor testing prior to ablation should be considered.

Treatment Gaps & Future Research
In the past several years, there have been multiple studies, including high-quality RCTs, evaluating the efficacy of genicular RFN. These studies have included pain scales and validated measures of function at up to 12 months of follow-up. Further studies will enable the ideal use of this treatment modality. Further research topics should include the examination of demographic factors (eg BMI, gender, severity of OA), improve patient selection, the utility of prognostic blocks and repeat RFN. In general, the ideal timing of RFN in the setting of a multimodal management algorithm should also be established. 122,123 Long-term outcomes, beyond a year, will also be important due to the chronic nature of the conditions typically treated with this modality.

Consensus Statement
Genicular nerve radiofrequency neurotomy may be used for the treatment of osteoarthritis related and post-surgical knee joint pain. GRADE II-1 B.

Current Available Evidence of Hip Joint Radiofrequency Neurotomy
The innervation of the hip was first studied and described in the mid-nineteenth century. German anatomist Rüdinger was a pioneer in describing the innervation of the large joints, including the shoulder, knee, and hip. 124 Rüdinger's work laid the framework for surgical denervation DovePress techniques and interventional pain procedures. Further study and understanding of the articular branches of the hip was elucidated by Gardner in the 1940s. 125 The evolution of RFN techniques has renewed the interest in hip pain treatment with RF techniques that maximize benefit while avoiding complications. Recent cadaveric dissections have shown notable anatomic variability with the location of articular branches from femoral (FN), obturator (ON), and accessory obturator nerves. 126 The anteromedial capsule of the hip is supplied by the branches of the obturator nerve, while the anterior capsule is innervated by branches of the femoral nerve. The sciatic nerve provides articular branches to the hip, posteriorly. Current ablative techniques focus on targeting the anterior hip. The accessory obturator nerve (AON) has been studied in cadaveric dissections and is present in a minority of individuals (10-30%). 127,128 The contribution of the AON (if present) can vary. The neurovascular bundle (femoral artery, vein, and nerve) is vulnerable to potential injury when targeting the obturator branches. Traditionally, this risk was mitigated by approaching the inferior aspect of the ischium from medial or lateral trajectories with the goal of passing underneath the bundle. The challenge with fluoroscopic guidance is that patients can have anatomic variations of the local neurovascular structures, which may result in bleeding and/or nerve injury. A thorough understanding of the anatomy of the articular branches, adjacent neurovascular structures, and needle approaches must be considered in order to optimize outcomes while decreasing adverse events.

Current Available Evidence of Hip Radiofrequency Neurotomy
The goal of hip RFN is to target major articular innervation to the anterior hip joint. RFN of hip articular branches was first described by Okada in 1981. 128 He subsequently reported successful results in a series of 15 patients with neurotomy of the articular branches anteriorly (femoral and obturator) and posteriorly (sciatic). 129 These early studies led to more robust investigation and interest in RFN for refractory hip pain. As hip RFN techniques evolved, neurotomy of both the femoral and articular branches became standard practice.
With the evolution of ultrasound technology and increased frequency of use in pain medicine, this modality is increasingly being used to increase accuracy and avoid complications. By no means does ultrasound replace fluoroscopy for hip RFN. Rather, it is often used in conjunction with fluoroscopy to aid in needle placement. Ultrasound may allow the proceduralist to avoid the femoral neurovascular bundle, decreasing the incidence of bleeding and nerve injury. These studies also show that it is imperative that motor testing is performed prior to neurotomy, as repositioning of cannula at the incisura acetabuli may be necessary to avoid the ON as it courses through the obturator foramen. Studies of hip RFN are summarized in Table 8.

Procedure Technique
Careful consideration and shared risk decision-making must be taken in regard to a patient's comorbidities and anticoagulation status. A paucity of data exists regarding best practices around anti-coagulation management for hip RFN. Many practitioners do not interrupt anticoagulants for diagnostic blocks and subsequent RFN, while others may stop these medications for the RFN portion or even both procedures. Larger cannula size may increase the risk of bleeding, particularly when targeting the ON branches, which run in close proximity to the femoral neurovascular bundle.
Patient body habitus and mobility are also important considerations. In the morbidly obese (BMI >40), it can be extremely difficult to place needles comfortably and easily. The patient must be able to tolerate being in a supine position for a prolonged period of time and have the ability to extend at the hip. If a patient is unable to tolerate these positions, RFN is likely to be challenging or not possible. At a minimum, fluoroscopy is needed to ensure proper identification of hip bony landmarks and to navigate challenging anatomy. Multiple studies have described a combined fluoroscopy and ultrasound technique that may improve safety and decrease the risk of vascular and/or nerve injury. [132][133][134][135] There is a paucity of data when it comes to prognostic value of hip articular branch blocks. Despite this, it is recommended that patients undergo a diagnostic block before being considered for neurotomy. This is largely due to the multitude of pain generators that may cause pain in the hip area including tendinopathy, bursitis, and lumbosacral pathology. A minority of studies have used relief following intraarticular hip injections as selection criteria for RFN. 130,136 Given the anatomic variability of articular branches, larger needles (21G or larger) are preferred. With conventional RFN, cannulae with a 10 mm active tip or larger is optimal. Cooled RFN is an alternative technique that may be https://doi.org/10.2147/JPR.S325665

DovePress
Journal of Pain Research 2021:14 superior given its increased volume of ablated tissue. Prior to neurotomy, we recommend that motor testing be performed to rule out proximity to the obturator or femoral nerves. Sensory testing can also be helpful in confirming proximity to the articular branches. Lastly, multiple neurotomy lesions of the ON and FN articular nerves should be considered given their unpredictable course.

Best Practices Summary
• At a minimum, fluoroscopy is necessary to ensure proper identification of hip bony landmarks and to navigate challenging anatomy. More investigation is required to determine the optimal use of ultrasound in hip denervation. Ultrasound is often used in conjunction with fluoroscopy for optimal needle placement.
• Patient body habitus and mobility are also important considerations. In the morbidly obese (BMI >40), it can be extremely difficult to place needles comfortably and easily. Patients must be able to lie supine with the hip in neutral extension. • Diagnostic blocks should be performed prior to neurotomy but data implying their prognostic value is limited. • Neurotomy of both the femoral and articular branches has become standard practice using lateral to medial approaches with the patient in the supine position ( Figure 8). • Evidence best supports the use of conventional RF at 80 degrees for 90 seconds, although efficacy for cooled-RF has been shown in recent cohort and case series. Retrospective cohort study A follow-up study looking at RFN feasibility focused primarily on the obturator articular branches, and to a lesser extent the femoral articular branches. 14 patients with various diagnoses leading to chronic hip pain received either an intraarticular injection or obturator articular block with a local anesthetic.
Those with groin and thigh pain had only obturator articular neurotomy. Those who also had trochanteric (lateral) pain also received a second neurotomy for the femoral articular branches. 12 patients (86%) reported at least 50% relief of pain for 1 to 11 months.

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• Larger lesion size is preferred given the anatomic variability of ON and FN articular branches.
Multiple neurotomy lesions at each site will likely increase the procedure's success.

Treatment Gaps & Future Research
Further investigation is needed to determine the optimal patient selection and protocol for improving outcomes. A review of the available literature found variable outcomes with regard to pain reduction ranging from 8 days to 3 years. 137 Anatomical variations of the FN, ON, and AON are certainly factors in the success of neurotomy. Additionally, RFN modality (cooled vs traditional), number of lesions, and cannula size are also important.

Consensus Statement
Hip joint radiofrequency neurotomy targeting the obturator and femoral nerve branches may be used for the treatment of hip joint pain following diagnostic blocks. GRADE II-1 B.

Occipital Nerve Radiofrequency Neurotomy
Occipital RFN is used for the treatment of chronic occipital neuralgia (ON) and posterior headache syndromes, including refractory migraine. ON is considered to be rare, while also challenging to diagnosis and treat. Trauma, irritation, and entrapment of the greater (GON), lesser (LON) and/or third occipital (TON) nerves have been suggested as the etiology of ON, which may present as lancinating pain along the respective nerve distributions. Physical examination findings include occipital tenderness, palpable trigger points at the emergence of the greater occipital nerve or in the distribution of C2, and positive Tinel's sign over the occiput at the location of the greater and lesser occipital nerves. 138 In lieu of diagnostic imaging findings, positive response to landmark guided or image-guided diagnostic block of the occipital nerves is confirmatory for the diagnosis, while the mainstay of treatment is considered to be a landmark or image guided corticosteroid injection. While RFN has been utilized in the treatment of ON, it has not garnered universal acceptance. Various modalities of RFN have been described including CRF, PRF, and WCRF.   Table 9.

Procedure Techniques
Published

Treatment Gaps
Further research is needed to best understand the optimal protocol for diagnostic block, the use of image guidance for occipital RFN, the optimal procedure techniques, and timetable for repeat procedures in successfully treated patients.

Future Research
Research and evidence gaps exist for occipital nerve pulsed radiofrequency (PRF). PRF allows for the application of radiofrequency current at lower temperatures, thereby minimizing the damage to surrounding tissue, nerve or vasculature. They may be the preferred technique given the superficial location of the occipital nerves. Further research on PRF is needed to determine the efficacy and safety of this treatment modality, and how it compares to CRF and WCRF. Although several studies have demonstrated the efficacy of both continuous and pulsed RF within the range of 6 weeks to 6 months more evidence is clearly needed.

Consensus Statement
Occipital neurotomy may be selectively offered for the treatment of occipital neuralgia pain when greater or lesser nerves have been identified as the etiology of pain via diagnostic blocks. GRADE II-2 C.

Conclusion
The use of radiofrequency ablation to treat pain is an established therapy that continues to evolve. This best practice document gives an evaluation as to the current evidence and recommendations. Going forward, these recommendations will be updated as new data is produced by either high-level studies or from large registries. Future guidelines will be modified as evidence is built, innovations arrive at the technology, and new ideas are presented to continue to improve patient safety and efficacy.

Acknowledgments
The authors would like to thank Abbott Laboratories for a generous educational grant for the development of this and other Best Practices Guidelines for interventional procedures currently relevant to our field. This manuscript was developed through a collaboration with the American Society of Pain & Neuroscience (ASPN) and its leadership. The authors are grateful for their tireless support and guidance. Illustrations were used with permission from Min A. Lee.

Disclosure
Dr David W Lee reports grants from Abbott, during the conduct of the study; is a member of speakers Bureau for Abbott Neuromodulation, outside the submitted work. Dr Scott Pritzlaff reports personal fees from Nalu Medical, personal fees from EBT Medical, personal fees from SPR Therapeutics, outside the submitted work. Dr Jonathan M Hagedorn reports personal fees from Abbott, personal fees from Boston Scientific, personal fees from Nevro, personal fees from Speranza Therapeutics, outside the submitted work. Dr Jordan Tate reports personal fees from Abbott. Dr Dawood Sayed reports personal fees from Abbott, personal fees from Medtronic, personal fees from Nevro, PainTeq, Spr, and Vertos, during the conduct of the study. Dr Timothy R Deer reports personal fees from Abbott; also his institution research received funding from Avanos, outside the submitted work. The authors report no other conflicts of interest in this work.