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Overexpression of miR-381 relieves neuropathic pain development via targeting HMGB1 and CXCR4

Li-Ying Zhan1, Shao-Qing Lei1, Bin-Hong Zhang2

  • 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 25, 2018
PubMed

Insights

MicroRNA-381 (miR-381) levels decrease in neuropathic pain. Restoring miR-381 reduces pain and inflammation by targeting HMGB1 and CXCR4, offering a potential therapeutic strategy for neuropathic pain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pain Research

Background:

  • MicroRNAs (miRNAs) are key regulators in neuropathic pain.
  • Neuroinflammation significantly drives neuropathic pain progression.
  • The specific role of miR-381 in neuropathic pain is largely unknown.

Purpose of the Study:

  • To investigate the role of miR-381 in neuropathic pain development.
  • To elucidate the molecular mechanisms underlying miR-381's effects.
  • To assess miR-381's therapeutic potential in a rat model of chronic sciatic nerve injury.

Main Methods:

  • Established a chronic sciatic nerve injury (CCI) rat model.
  • Quantified miR-381 expression levels in CCI rats.
  • Overexpressed miR-381 and assessed its impact on pain behaviors and inflammatory cytokines (IL-6, IL-10, TNF-α).
  • Utilized bioinformatics analysis to predict and experimentally validate miR-381 targets (HMGB1, CXCR4).
  • Investigated the effects of silencing HMGB1 and CXCR4 on neuropathic pain.

Main Results:

  • miR-381 expression was significantly downregulated in CCI rats.
  • Overexpression of miR-381 markedly reduced mechanical and thermal hyperalgesia.
  • miR-381 overexpression suppressed the expression of inflammatory cytokines IL-6, IL-10, and TNF-α.
  • HMGB1 and CXCR4 were identified as direct targets of miR-381 and their expression increased time-dependently in CCI rats.
  • Silencing HMGB1 and CXCR4 alleviated neuropathic pain progression in CCI rats.

Conclusions:

  • miR-381 plays an inhibitory role in neuropathic pain development.
  • miR-381 exerts its effects by targeting and downregulating HMGB1 and CXCR4.
  • Restoring miR-381 levels presents a potential therapeutic strategy for neuropathic pain by modulating neuroinflammation and key molecular targets.
Keywords:
CXCR4HMGB1Neuropathic painmiR-381

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