MiR-183-5p Alleviates Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of TREK-1

Neurochem Res. 2018 Jun;43(6):1143-1149. doi: 10.1007/s11064-018-2529-4. Epub 2018 May 7.

Abstract

MicroRNAs have been implicated in nerve injury and neuropathic pain. In the previous study we had shown that miR-96 can attenuate neuropathic pain through inhibition of Nav1.3. In this study, we investigated the role of miR-183, a same cluster member of microRNA with miR-96, in neuropathic pain and its potential mechanisms. We found that the expression level of miR-183-5p in dorsal root ganglion was decreased with the development of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). By contrast, the TREK-1, a K+ channel, was increased. Further investigation identified that intrathecal injection of miR-183-5p mimic efficiently ameliorated neuropathic pain and inhibited the expression of TREK-1, a predicted target gene of miR-183-5p. Luciferase assays confirmed the binding of miR-183-5p and TREK-1. In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain. Our findings suggested that miR-183-5P participated in the regulation of CCI-induced neuropathic pain through inhibiting the expression of TREK-1.

Keywords: Chronic constriction injury; Dorsal root ganglion; MiR-183-5p; Neuropathic pain; TREK-1.

MeSH terms

  • Animals
  • Constriction, Pathologic / genetics
  • Ganglia, Spinal / metabolism
  • Hyperalgesia / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neuralgia / genetics*
  • Neuralgia / physiopathology
  • Peripheral Nerve Injuries / genetics*
  • Peripheral Nerve Injuries / physiopathology
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Rats, Sprague-Dawley
  • Sciatic Nerve / injuries
  • Sciatic Neuropathy / metabolism

Substances

  • MIRN183 microRNA, rat
  • MicroRNAs
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1