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Down-regulation of microRNA-382-5p reduces neuropathic pain by targeting regulation of dual specificity phosphatase-1

  • Anjie Xu (Department of Pain Management, Zhongnan Hospital of Wuhan University) ;
  • Huili Shen (Department of Anaesthesia and Surgery, Hebei Maternity Hospital) ;
  • Shasha Mei (Department of Anesthesiology and Surgery, Shengli Oilfield Central Hospital) ;
  • Zhongwei Wang (Department of Pain, Shengli Oilfield Central Hospital) ;
  • Qiuyi Xie (Department of Pain, Shengli Oilfield Central Hospital) ;
  • Huaqing Cui (Department of Anesthesiology, Dongying Hospital of Traditional Chinese Medicine) ;
  • Yunchao Chu (Department of Pain, Shengli Oilfield Central Hospital) ;
  • Baihe Feng (Department of Anesthesiology, The First Hospital of China Medical University)
  • 투고 : 2024.06.17
  • 심사 : 2024.09.09
  • 발행 : 2024.10.01

초록

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions: Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

키워드

과제정보

This study was funded by Expenditures on science and education projects (IIT202202501).

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