Mechanism of Incisional Pain: Novel Finding on Long Noncoding RNA XIST/miR-340-5p/RAB1A Axis

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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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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https://painphysicianjournal.com/current/pdf?article=MTgwMw%3D%3D&journal=71

January 2018 - Pain Physician ◽

10.36076/ppj.2012/15/e995 ◽

2012 ◽

Vol 6;15 (6;12) ◽

pp. E995-E1006

Author(s):

Prof. Yun-Qing Li

Keyword(s):

Neuropathic Pain ◽

Dorsal Horn ◽

Inflammatory Cytokines ◽

Glial Cells ◽

Mechanical Allodynia ◽

Spinal Dorsal Horn ◽

Pain Behavior ◽

Repeated Treatment ◽

Single Bolus ◽

Spinal Dorsal

Background: Current treatments for neuropathic pain are far from satisfactory. Considering the essential contribution of central immune factors to the pathogenesis of neuropathic pain, targeting inflammatory response is well accepted as an effective strategy for treating neuropathic pain. Triptolide has a long history in traditional Chinese medicine for treating inflammatory diseases and has been proven to inhibit cytokines released from glial cells. Objective: In the present study, we tested whether systemic treatment with triptolide could prevent or attenuate nocifensive behaviors associated with neuropathic pain. We further tried to explore the underlying mechanism of the potential anti-allodynia effect of triptolide. Study Design: A randomized, double blind, controlled animal trial. Methods: Triptolide was administered systemically in a rat model of neuropathic pain induced by spinal nerve ligation (SNL) in the single bolus and repeated treatment manners. In the single bolus treatment experiment, triptolide (30 μg/kg, 100 μg/kg, 300 μg/kg) or vehicle was given to SNL and sham-operated rats once on day 1 or on day 10 after surgery (n = 6 each). In the repeated treatment study, prophylactic treatment with triptolide (30 μg/kg, 100 μg/kg, 300 μg/kg) was given to rats during the period of day -3 (3 days prior to SNL) to day 7 (7 days post-SNL) inclusively (n = 6 each). Another set of SNL and sham rats on postoperative day 10 received treatment with triptolide (30 μg/kg, 100 μg/kg, 300 μg/kg) or vehicle during the period of days 11–20 inclusively (n = 6 each), to assess potential reversal of established pain behavior. Mechanical allodynia of the rats was tested with von Frey filaments. Astrocytic and microglial activation in the spinal dorsal horn was evaluated with immunofluorescent histochemistry. Phosphorylation of mitogen-activated protein kinases (MAPKs), and expression of inflammatory cytokines (interleukin-6, interleukin-1beta, monocyte chemotactic protein-1, and tumor necrosis factor-alpha) were examined with Western blot analysis and real-time reverse transcription polymerase chain reaction study. Results: A single bolus treatment with triptolide could neither prevent the induction nor reverse the maintenance of SNL-induced mechanical allodynia. However, repeated administration of triptolide dose-dependently inhibited neuropathic pain behavior in both preventative and interventional paradigms. Triptolide hampered SNL-induced activation of glial cells (astrocytes and microglia) in the spinal dorsal horn without influencing neurons. In addition, SNL-induced phosphorylation of MAPKs could be inhibited by triptolide. Furthermore, up-regulated expression of inflammatory cytokines in neuropathic pain states could be remarkably blocked by triptolide. Limitations: The direct target site (such as a specific receptor) of triptolide is still to be determined. In addition, triptolide could not completely block the SNL-induced mechanical allodynia. Conclusions: Our data suggest that triptolide may be a potential novel treatment for neuropathic pain through modulating immune response in the spinal dorsal horn. Key words: Triptolide, neuropathic pain, spinal dorsal horn, astrocyte, microglia, MAPK.

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

Neuroscience ◽

10.1016/j.neuroscience.2018.04.028 ◽

2018 ◽

Vol 382 ◽

pp. 14-22 ◽

Cited By ~ 2

Author(s):

Ruijuan Guo ◽

Huili Li ◽

Xueyang Li ◽

Yuqing Sun ◽

Huihui Miao ◽

...

Keyword(s):

Postoperative Pain ◽

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Postsynaptic Membrane ◽

Spinal Dorsal

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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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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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XIST: A Meaningful Long Noncoding RNA in NSCLC Process

Current Pharmaceutical Design ◽

10.2174/1381612826999201202102413 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yujie Shen ◽

Yexiang Lin ◽

Kai Liu ◽

Jinlan Chen ◽

Juanjuan Zhong ◽

...

Keyword(s):

Therapeutic Target ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Critical Role ◽

Biological Functions ◽

Potential Therapeutic Target ◽

Considerable Evidence ◽

Lncrna Xist ◽

Nsclc Patients ◽

The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

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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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