Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain

The objective of this study is to investigate the effect of long noncoding RNA (lncRNA) XIST on postoperative pain and inflammation of plantar incision pain (PIP) in rats and its underlying mechanisms. PIP rat models were established by plantar incision. Rats in the sham group were subjected to povidone-iodine scrubbing, and no incision was made. To explore the role of XIST/ miR-340-5p/RAB1A in postoperative pain and inflammation, PIP rats were separately or simultaneously injected with lentivirus containing sh-NC, sh-XIST, mimic NC, miR-340-5p mimic, inhibitor NC, miR-340-5p inhibitor, pcDNA3.1, or pcDNA3.1-RAB1A through an intrathecal catheter. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values of rats in each group were assessed to evaluate the pain behavior. RT-qPCR and Western blot were utilized to determine the levels of XIST, miR-340-5p, RAB1A, and NF-κB pathway-related proteins (p-IκBα, IκBα, p-p65, and p65). The concentrations of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in rat spinal dorsal horn tissues were inspected by ELISA. H and E staining was applied to observe the pathological changes of neurons in the spinal dorsal horn, TUNEL staining to detect neuronal apoptosis, and immunohistochemistry to measure RAB1A level. Plantar incision surgery caused decreased PWT and PWL values, enhanced levels of XIST, RAB1A, and inflammatory cytokines, along with an increased proportion of apoptotic neurons. The pain sensitivity and inflammation of rats were motivated after plantar incision surgery. Intrathecal injection of sh-XIST or miR-340-5p mimic ameliorated the pain and inflammation of PIP rats, while silencing of miR-340-5p or overexpression of RAB1A partly reversed the effect of sh-XIST on PIP rats. XIST targeted miR-340-5p and miR-340-5p negatively regulated RAB1A. The XIST/ miR-340-5p/RAB1A axis activated the NF-κB signaling pathway. LncRNA XIST aggravates inflammatory response and postoperative pain of PIP rats by activating the NF-κB pathway via the miR-340-5p/RAB1A axis.

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Allopregnanolone suppresses mechanical allodynia and internalization of neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain model

The Korean Journal of Pain ◽

10.3344/kjp.2018.31.1.10 ◽

2018 ◽

Vol 31 (1) ◽

pp. 10 ◽

Cited By ~ 5

Author(s):

Masahide Fujita ◽

Taeko Fukuda ◽

Yasuhiro Sato ◽

Toshifumi Takasusuki ◽

Makoto Tanaka

Keyword(s):

Postoperative Pain ◽

Dorsal Horn ◽

Mechanical Allodynia ◽

Spinal Dorsal Horn ◽

Pain Model ◽

Spinal Dorsal ◽

Neurokinin 1

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The effects of dexmedetomidine and halothane on Fos expression in the spinal dorsal horn using a rat postoperative pain model

Neuroscience Letters ◽

10.1016/s0304-3940(03)00309-4 ◽

2003 ◽

Vol 343 (1) ◽

pp. 45-48 ◽

Cited By ~ 27

Author(s):

Noriko Shimode ◽

Tetsuo Fukuoka ◽

Masaaki Tanimoto ◽

Chikara Tashiro ◽

Atsushi Tokunaga ◽

...

Keyword(s):

Postoperative Pain ◽

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Pain Model ◽

Spinal Dorsal ◽

Fos Expression

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Single Intraperitoneal Injection of Low-Dose Ketamine Pretreatment Alleviates Mechanical Hyperalgesia and Downregulates the Expression of Inflammatory Cytokines in Spinal Dorsal Horn of Rats

Journal of Anesthesia and Perioperative Medicine ◽

10.24015/japm.2015.0032 ◽

2015 ◽

Vol 2 (5) ◽

pp. 236-243

Author(s):

Li Xu ◽

Yu Shen ◽

Lin Liu ◽

Yin Cui ◽

Xiao-Ping Gu ◽

...

Keyword(s):

Dorsal Horn ◽

Inflammatory Cytokines ◽

Intraperitoneal Injection ◽

Spinal Dorsal Horn ◽

Low Dose ◽

Mechanical Hyperalgesia ◽

Spinal Dorsal ◽

Single Intraperitoneal Injection

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Faculty Opinions recommendation of Spread of excitation across modality borders in spinal dorsal horn of neuropathic rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1105023.561186 ◽

2008 ◽

Author(s):

Nanna Finnerup

Keyword(s):

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Spinal Dorsal ◽

Spread Of Excitation

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Faculty Opinions recommendation of Innocuous, not noxious, input activates PKCgamma interneurons of the spinal dorsal horn via myelinated afferent fibers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1120062.576194 ◽

2008 ◽

Author(s):

Nanna Finnerup

Keyword(s):

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Spinal Dorsal ◽

Afferent Fibers

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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

Journal of Neuroinflammation ◽

10.1186/s12974-021-02168-1 ◽

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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