Effects of pre-emptively administered nociceptin on the development of thermal hyperalgesia induced by two models of experimental mononeuropathy in the rat

Brain Res. 2000 Jul 21;871(2):192-200. doi: 10.1016/s0006-8993(00)02480-x.

Abstract

Pre-emptive analgesia is thought to be produced by the prevention of spinal facilitation evoked by nociceptive input to the spinal cord. Opioid receptor-like 1 (ORL1) receptor agonist has been reported to inhibit the development of spinal facilitation. We investigated the effect of nociceptin, an ORL1 receptor agonist, on the development of thermal hyperalgesia and the expression of Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn induced by two neuropathic pain models, the chronic constriction injury model and the partial sciatic nerve injury model. Chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. Partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 10 min before the nerve injury. The anti-hyperalgesic effect of drugs was evaluated by the measurement of the paw withdrawal latency (PWL) against thermal nociceptive stimulation. The PWLs of the injured paws were measured 7, 14 and 21 days after the nerve injury. Expression of Fos-LI was examined 2 h after the nerve injury. Intrathecal injection of nociceptin significantly delayed the development of thermal hyperalgesia and decreased the expression of Fos-LI induced by chronic constriction injury, but not that induced by partial sciatic nerve injury. These data indicate that pre-emptive administration of nociceptin might be one strategy for the prevention of the development of neuropathic pain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Administration Schedule
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology*
  • Injections, Spinal
  • Male
  • Nociceptin
  • Opioid Peptides / metabolism
  • Opioid Peptides / pharmacology*
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / pathology
  • Posterior Horn Cells / physiopathology
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Neuropathy / pathology
  • Sciatic Neuropathy / physiopathology*
  • Somatosensory Disorders / chemically induced*
  • Somatosensory Disorders / pathology
  • Somatosensory Disorders / physiopathology*
  • Vasodilator Agents / metabolism
  • Vasodilator Agents / pharmacology*

Substances

  • Opioid Peptides
  • Proto-Oncogene Proteins c-fos
  • Vasodilator Agents