Effect of supraspinal Nocistatin on Nociceptin/Orphanin FQ antagonism of selective opioid analgesia

Nocistatin and Nociceptin/Orphanin FQ are two neuropeptides derived from the same precursor protein, pre-pro-Nociceptin. Nocistatin does not bind to Nociceptin/Orphanin FQ peptide (NOP) receptor but it antagonizes the allodynic and hyperalgesic effect of intrathecal (i.t.) Nociceptin. In this study, we examined the effect of Nocistatin on nociception and opioid analgesia by itself and the nociceptive effect of Nociceptin and antagonistic effect of nociceptin on opioid receptors in tail flick test when given the i.c.v. route. More precisely, supraspinal Nocistatin by itself had no significative effect on nociception and opioid analgesia in the tail flick test but, at the dose of 0.5 ng/rat, it reversed the nociceptive effect of Nociceptin and also the antagonistic effect of Nociceptin against analgesia caused by the selective opioid agonists: DAMGO, DPDPE, Deltorphin II and U50 488H. These data suggest that Nocistatin antagonizes the effect of Nociceptin on opioid analgesia and could play an important role in the regulation of nociceptive transmission.