{'fraction_non_alphanumeric': 0.03034825870646766, 'fraction_numerical': 0.014427860696517412, 'mean_word_length': 5.057228915662651, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats.

BACKGROUND
The activation of mitogen-activated protein kinases (MAPKs) have been observed in synaptic plasticity processes of learning and memory in neuropathic pain. Cerebrospinal fluid-contacting nucleus (CSF-CN) has been identified with the onset and persistence of neuropathic pain. However, whether extracellular signal-regulated protein kinase 5 (ERK5), a member of MAPKs, in CSF-CN participates in neuropathic pain has not been studied yet.


OBJECTIVE
The aim of the present study was to identify the role of ERK5 in CSF-CN on the formation and development of neuropathic pain, and to investigate its possible mechanism.


STUDY DESIGN
Controlled animal study.


SETTING
University laboratory.


METHODS
After a chronic constriction injury (CCI) model was produced, BIX02188 was dissolved in 1% DMSO and injected into the lateral ventricles LV in a volume of 3 μl with different doses (0.1 μg, 1 μg, 10 μg). Mechanical allodynia and thermal hypersensitivity behavioral test, immunofluorescence, and western blot technique were used in this research.


RESULT
Following CCI, mechanical allodynia and thermal hypersensitivity were developed within a day, peaked at 14 days, and persisted for 21 days. ERK5 was remarkably activated by CCI in CSF-CN. Moreover, selective inhibiting of p-ERK5 expression in CSF-CN by BIX02188 could significantly relieve CCI-induced mechanical allodynia and thermal hypersensitivity, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in CSF-CN.


LIMITATIONS
More underlying mechanism(s) of the role of ERK5 in CSF-CN on the formation and development of neuropathic pain will be needed to explore in future research.


CONCLUSION
These findings suggest activation of ERK5 in CSF-CN might contribute to the onset and development of neuropathic pain and its role might be partly accomplished by p-CREB.