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

Pre-emptive analgesia is thought to be produced by the prevention of spinal facilitation evoked by nociceptive input to the spinal cord. Opioid recept or-like 1 (ORL1) receptor agonist has been reported to inhibit the developm ent of spinal facilitation. We investigated the effect of nociceptin, an OR L1 receptor agonist, on the development of thermal hyperalgesia and the exp ression of Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn ind uced 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 ner ve. Partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intratheca lly 10 min before the nerve injury. The anti-hyperalgesic effect of drugs w as evaluated by the measurement of the paw withdrawal latency (PWL) against thermal nociceptive stimulation. The PWLs of the injured paws were measure d 7, 14 and 21 days after the nerve injury. Expression of Fos-LI was examin ed 2 h after the nerve injury. Intrathecal injection of nociceptin signific antly delayed the development of thermal hyperalgesia and decreased the exp ression of Fos-LI induced by chronic constriction injury, but not that indu ced by partial sciatic nerve injury. These data indicate that pre-emptive a dministration of nociceptin might be one strategy for the prevention of the development of neuropathic pain. (C) 2000 Elsevier Science B.V. All rights reserved.