scholarly journals Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

SLEEP ◽  
2014 ◽  
Vol 37 (9) ◽  
pp. 1513-1523 ◽  
Author(s):  
Chun-Ta Huang ◽  
Rayleigh Ping-Ying Chiang ◽  
Chih-Li Chen ◽  
Yi-Ju Tsai
Keyword(s):  
Neuropathic Pain ◽  
Sleep Deprivation ◽  
Median Nerve ◽  
Nerve Injury ◽  
Microglial Activation ◽  
Melatonin Secretion ◽  
Median Nerve Injury

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury–induced Mechanical Hypersensitivity and Glial Extracellular Signal–regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus

2016 ◽  
Vol 125 (6) ◽  
pp. 1202-1218 ◽  
Author(s):  
Chun-Ta Huang ◽  
Seu-Hwa Chen ◽  
June-Horng Lue ◽  
Chi-Fen Chang ◽  
Wen-Hsin Wen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Median Nerve ◽  
Nerve Injury ◽  
Type A ◽  
Aminobutyric Acid ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Acid Type ◽  
Extracellular Signal ◽  
Median Nerve Injury

Abstract Background Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. Methods We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. Results At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. Conclusions Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.

scholarly journals Pulsed radiofrequency of the median nerve under ultrasound guidance for management of intractable neuropathic pain

2019 ◽  
Vol 47 (8) ◽  
pp. 3978-3984
Author(s):  
Yoo Jung Park ◽  
Man Hee Lee ◽  
So Young Kwon
Keyword(s):  
Neuropathic Pain ◽  
Median Nerve ◽  
Nerve Injury ◽  
Skin Color ◽  
Therapeutic Option ◽  
Pain Clinic ◽  
Intractable Pain ◽  
Pulsed Radiofrequency ◽  
Ultrasound Guided ◽  
Median Nerve Injury

A median nerve injury in the forearm may lead to devastating sequelae if left untreated. Even with appropriate treatments involving microsurgical techniques and postoperative care, patients may still experience lasting neuropathic pain that significantly reduces their quality of life. Pulsed radiofrequency (PRF) is widely performed to alleviate such neuropathic pain caused by trauma. A 47-year-old man visited our pain clinic with allodynia, hyperalgesia, paresthesia, skin color changes, and atrophy in the right forearm. In the orthopedic department, the patient was treated by neurectomy of the median nerve to manage the intractable pain. However, the effect was unsatisfactory. The fourth median nerve block performed in our pain clinic after neurectomy produced good results, and ultrasound-guided PRF of the median nerve was performed. The patient showed 80% relief of symptoms within 5 hours after the procedure. The visual analog scale score for the forearm decreased from 8/10 to 1/10. This case suggests that ultrasound-guided PRF can be a therapeutic option for the management of refractory neuropathic pain after neurectomy in patients with a median nerve injury.

scholarly journals Calcitonin gene-related peptide regulates spinal microglial activation through the histone H3 lysine 27 trimethylation via enhancer of zeste homolog-2 in rats with neuropathic pain

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Qi An ◽  
Chenyan Sun ◽  
Ruidi Li ◽  
Shuhui Chen ◽  
Xinpei Gu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Dorsal Horn ◽  
Microglial Activation ◽  
Microglial Cells ◽  
Gene Promoters ◽  
Spinal Dorsal ◽  
Related Peptide ◽  
Calcitonin Gene

Abstract Background Calcitonin gene-related peptide (CGRP) as a mediator of microglial activation at the transcriptional level may facilitate nociceptive signaling. Trimethylation of H3 lysine 27 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that regulates inflammatory-related gene expression after peripheral nerve injury. In this study, we explored the relationship between CGRP and H3K27me3 in microglial activation after nerve injury, and elucidated the underlying mechanisms in the pathogenesis of chronic neuropathic pain. Methods Microglial cells (BV2) were treated with CGRP and differentially enrichments of H3K27me3 on gene promoters were examined using ChIP-seq. A chronic constriction injury (CCI) rat model was used to evaluate the role of CGRP on microglial activation and EZH2/H3K27me3 signaling in CCI-induced neuropathic pain. Results Overexpressions of EZH2 and H3K27me3 were confirmed in spinal microglia of CCI rats by immunofluorescence. CGRP treatment induced the increased of H3K27me3 expression in the spinal dorsal horn and cultured microglial cells (BV2) through EZH2. ChIP-seq data indicated that CGRP significantly altered H3K27me3 enrichments on gene promoters in microglia following CGRP treatment, including 173 gaining H3K27me3 and 75 losing this mark, which mostly enriched in regulation of cell growth, phagosome, and inflammation. qRT-PCR verified expressions of representative candidate genes (TRAF3IP2, BCL2L11, ITGAM, DAB2, NLRP12, WNT3, ADAM10) and real-time cell analysis (RTCA) verified microglial proliferation. Additionally, CGRP treatment and CCI increased expressions of ITGAM, ADAM10, MCP-1, and CX3CR1, key mediators of microglial activation in spinal dorsal horn and cultured microglial cells. Such increased effects induced by CCI were suppressed by CGRP antagonist and EZH2 inhibitor, which were concurrently associated with the attenuated mechanical and thermal hyperalgesia in CCI rats. Conclusion Our findings highly indicate that CGRP is implicated in the genesis of neuropathic pain through regulating microglial activation via EZH2-mediated H3K27me3 in the spinal dorsal horn.

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