The Korean Journal of Pain

  • 제37권4호
  • /
  • Pages.320-331
  • /
  • 2024
  • /
  • 2005-9159(pISSN)
  • /
  • 2093-0569(eISSN)
대한통증학회 (The Korean Pain Society)
권호 표지
DOI QR코드

DOI QR Code

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
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

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).

참고문헌

  1. Moini Zanjani T, Ameli H, Labibi F, Sedaghat K, Sabetkasaei M. The attenuation of pain behavior and serum COX-2 concentration by curcumin in a rat model of neuropathic pain. Korean J Pain 2014; 27: 246-52. 
  2. Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc 2015; 90: 532-45. 
  3. Reisig F, Harnik M. [Neuropathic pain: pharmacotherapy]. Ther Umsch 2020; 77: 274-280. German. 
  4. Elzahaf RA, Johnson MI, Tashani OA. The epidemiology of chronic pain in Libya: a cross-sectional telephone survey. BMC Public Health 2016; 16: 776. 
  5. Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers 2017; 3: 17002. 
  6. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009; 19: 92-105. 
  7. Lopez-Gonzalez MJ, Landry M, Favereaux A. MicroRNA and chronic pain: from mechanisms to therapeutic potential. Pharmacol Ther 2017; 180: 1-15. 
  8. Xiang W, Jiang L, Zhou Y, Li Z, Zhao Q, Wu T, et al. The lncRNA Ftx/miR-382-5p/Nrg1 axis improves the inflammation response of microglia and spinal cord injury repair. Neurochem Int 2021; 143: 104929. 
  9. Yin X, Zheng W, He L, Mu S, Shen Y, Wang J. CircHIPK3 alleviates inflammatory response and neuronal apoptosis via regulating miR-382-5p/DUSP1 axis in spinal cord injury. Transpl Immunol 2022; 73: 101612. 
  10. Ashmwe M, Posa K, Ruhrnossl A, Heinzel JC, Heimel P, Mock M, et al. Effects of extracorporeal shockwave therapy on functional recovery and circulating miR-375 and miR-382-5p after subacute and chronic spinal cord contusion injury in rats. Biomedicines 2022; 10: 1630. 
  11. Cao S, Zhang D, Yuan J, Liu C, Zhou W, Zhang L, et al. MicroRNA and circular RNA expression in affected skin of patients with postherpetic neuralgia. J Pain Res 2019; 12: 2905-13. 
  12. Wang X, Jiang Y, Li J, Wang Y, Tian Y, Guo Q, et al. DUSP1 promotes microglial polarization toward M2 phenotype in the medial prefrontal cortex of neuropathic pain rats via inhibition of MAPK pathway. ACS Chem Neurosci 2021; 12: 966-78. 
  13. Liu LP, Zhang J, Pu B, Li WQ, Wang YS. Upregulation of JHDM1D-AS1 alleviates neuroinflammation and neuronal injury via targeting miR-101-3p-DUSP1 in spinal cord after brachial plexus injury. Int Immunopharmacol 2020; 89: 106962. 
  14. Li Z, Li A, Yan L, Yang T, Xu W, Fan P. Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury-induced neuropathic pain in rats by targeting miR-133a-3p/SRPK1 axis. Mol Med 2020; 26: 104. 
  15. Yoo SH, Lee SH, Lee S, Park JH, Lee S, Jin H, et al. The effect of human mesenchymal stem cell injection on pain behavior in chronic post-ischemia pain mice. Korean J Pain 2020; 33: 23-9. 
  16. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87-107. 
  17. Attal N, Jazat F, Kayser V, Guilbaud G. Further evidence for 'pain-related' behaviours in a model of unilateral peripheral mononeuropathy. Pain 1990; 41: 235-51. 
  18. Bakare AO, Owoyele BV. Antinociceptive and neuroprotective effects of bromelain in chronic constriction injury-induced neuropathic pain in Wistar rats. Korean J Pain 2020; 33: 13-22. 
  19. Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 2012; 13: 271-82. 
  20. Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH. An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol 2019; 234: 5451-65. 
  21. Kovanur Sampath K, Belcher S, Hales J, Thomson OP, Farrell G, Gisselman AS, et al. The role of microRNAs in neuropathic pain-a scoping review. Pain Rep 2023; 8: e1108. 
  22. Liu JC, Xue DF, Wang XQ, Ai DB, Qin PJ. MiR-101 relates to chronic peripheral neuropathic pain through targeting KPNB1 and regulating NF-κB signaling. Kaohsiung J Med Sci 2019; 35: 139-45. 
  23. Zhang YU, Ye G, Zhao J, Chen Y, Kong L, Sheng C, et al. Exosomes carried miR-181c-5p alleviates neuropathic pain in CCI rat models. An Acad Bras Cienc 2022; 94: e20210564. 
  24. Kuffler DP. Mechanisms for reducing neuropathic pain. Mol Neurobiol 2020; 57: 67-87. 
  25. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152(3 Suppl): S2-15. 
  26. Calvo M, Dawes JM, Bennett DL. The role of the immune system in the generation of neuropathic pain. Lancet Neurol 2012; 11: 629-42. 
  27. Taylor DM, Moser R, Regulier E, Breuillaud L, Dixon M, Beesen AA, et al. MAP kinase phosphatase 1 (MKP-1/DUSP1) is neuroprotective in Huntington's disease via additive effects of JNK and p38 inhibition. J Neurosci 2013; 33: 2313-25. 
  28. Zhang CG, Wan HQ, Ma KN, Luan SX, Li H. Identification of biomarkers related to neuropathic pain induced by peripheral nerve injury. J Mol Neurosci 2019; 69: 505-15. 
  29. Xuan C, Cui H, Jin Z, Yue Y, Cao S, Cui S, et al. Glutamine ameliorates hyperoxia-induced hippocampal damage by attenuating inflammation and apoptosis via the MKP-1/MAPK signaling pathway in neonatal rats. Front Pharmacol 2023; 14: 1096309. 
  30. Fan M, Wang C, Zhao X, Jiang Y, Wang C. Parthenolide alleviates microglia-mediated neuroinflammation via MAPK/TRIM31/NLRP3 signaling to ameliorate cognitive disorder. Int Immunopharmacol 2023; 120: 110287.