Effects of riluzole on P2X7R expression in the spinal cord in rat model of neuropathic pain

Neurosci Lett. 2016 Apr 8:618:127-133. doi: 10.1016/j.neulet.2016.02.065. Epub 2016 Mar 4.

Abstract

Neuropathic pain is becoming an intractable health threat, with its profound effect on quality of life, thus posing a major challenge to clinical therapy. Despite the reported efficacy of riluzole in some pain models, the underlying mechanism remains largely unknown. The present study aimed to assess the effects of riluzole in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Subsequent to model establishment, paw withdrawal latencies (PWLs) and the paw withdrawal mecha threshold (PWT) rapidly decreased, coupled with inhibited microglial activation and upregulated P2X7R expression in the spinal cord dorsal horn (SCDH). Following intraperitoneal administration of riluzole (4mg/kg) once daily for 5 consecutive days as from day 3 after surgery, the mechanical allodynia and thermal hyperalgesia in the hind limbs were significantly attenuated. In addition, riluzole downregulated P2X7R expression and inhibited microglial activation in SCDH. Our results indicated that riluzole is effective in alleviating neuropathic pain and inhibiting microglial activation, presumably via the downregulated P2X7R expression in SCDH.

Keywords: Microglia; Neuropathic pain; P2X7 receptor; Riluzole; Spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Constriction, Pathologic / complications
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Neuralgia / metabolism
  • Neuralgia / physiopathology
  • Purinergic P2X Receptor Antagonists / pharmacology*
  • Purinergic P2X Receptor Antagonists / therapeutic use
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X7 / metabolism*
  • Riluzole / pharmacology*
  • Riluzole / therapeutic use
  • Sciatic Nerve / injuries
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Spinal Cord Dorsal Horn / drug effects
  • Spinal Cord Dorsal Horn / metabolism
  • Up-Regulation

Substances

  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Riluzole