Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section.
We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092-2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED50 for reflex depression was 2.4 jig for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED50 for reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.
D000818:Animals; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D005079:Excipients; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D007278:Injections, Spinal; D018482:Muscle, Skeletal / Q000187:drug effects; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012044:Regression Analysis; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects; D000097629:Nociceptin