Interleukin-1beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel-associated acute pain syndrome

Glia ◽  
2018 ◽  
Vol 67 (3) ◽  
pp. 482-497 ◽  
Author(s):  
Xisheng Yan ◽  
Fen Li ◽  
Dylan W. Maixner ◽  
Ruchi Yadav ◽  
Mei Gao ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Acute Pain ◽  
Spinal Dorsal Horn ◽  
Pain Syndrome ◽  
Spinal Dorsal ◽  
Interleukin 1Beta

scholarly journals Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Miyuki Kurabe ◽  
Hidemasa Furue ◽  
Tatsuro Kohno
Keyword(s):  
Spinal Cord ◽  
Patch Clamp ◽  
Dorsal Horn ◽  
Acute Pain ◽  
Analgesic Effect ◽  
Spinal Dorsal Horn ◽  
Intravenous Lidocaine ◽  
Spinal Dorsal ◽  
Postsynaptic Currents

Abstract Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

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.

Driving effect of BDNF in the spinal dorsal horn on neuropathic pain

2021 ◽  
pp. 135965
Author(s):  
Zhou Wu ◽  
Xie Zhiping ◽  
Li Chengcai ◽  
Zelong Xing ◽  
Xie Shenke ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Spinal Dorsal

SNAP25/syntaxin4/VAMP2/Munc18-1 Complexes in Spinal Dorsal Horn Contributed to Inflammatory Pain

Neuroscience ◽  
2020 ◽  
Vol 429 ◽  
pp. 203-212 ◽  
Author(s):  
Xing-Lian Duan ◽  
Zhen Guo ◽  
Yong-Tao He ◽  
Yin-Xia Li ◽  
Yan-Ni Liu ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Inflammatory Pain ◽  
Spinal Dorsal Horn ◽  
Spinal Dorsal
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