Effects of intrathecally administered nociceptin, an opioid receptor- like1 receptor agonist, and N-methyl-D-aspartate receptor antagonists on the thermal hyperalgesia induced by partial sciatic nerve injury in the rat

Abstract

Background. Nociceptin is a 17-amino acid peptide and acts as a potent endogenous agonist of the opioid receptor-like1 receptor. Nociceptin is reported to depress glutamatergic transmission and to block the spinal facilitation that is thought to be mediated by the N-methyl-D-aspartate (NMDA) receptor. In the present study, the authors investigated the effect of intrathecally administered nociceptin and NMDA antagonists on the level of thermal hyperalgesia after partial sciatic nerve injury in the rat. Methods: Partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. The level of thermal hyperalgesia was evaluated by the difference score, which was calculated by subtracting the paw withdrawal latency against thermal nociceptive stimulation in the uninjured paw from that in the injured paw. Drugs were administered intrathecally 7 or 11 days after the nerve injury, and the level of thermal hyperalgesia was measured 5, 15, 30, 60, and 90 min after the drug injection. Results: Intrathecal injection of nociceptin, but not of NMDA antagonists, attenuated the level of thermal hyperalgesia in a dose-dependent manner at a dose of 0.17-17 nM (post-drug difference score: saline-treated rats, -4.9 ± 2.2 s; 17 nM nociceptin-treated rats, -1.3 ± 0.9 s). Conclusions: Intrathecal injection of nociceptin attenuated the level of thermal hyperalgesia induced by partial sciatic nerve injury, and NMDA receptor- dependent spinal facilitation does not play an important role in maintaining thermal hyperalgesia in rats with partial sciatic nerve injury.