Supraspinal nocistatin and its amide derivative antagonize the hyperalgesic effects of nociceptin in mice

Nocistatin (NST) and nociceptin (NCP)/orphanin FQ are new neuropeptides derived from the same precursor molecule, and which are involved in pain transmission. Nocistatin has been shown to antagonize several effects of nociceptin by acting on a different receptor. We examined the effects of supraspinal nocistatin and nocistatin amide, and their interaction with nociceptin on nociceptive behavior in mice, using hotplate response times. We found that both nocistatin and nocistatin amide did not change the response time compared to control mice, whereas increasing doses of nociceptin caused progressive shortening of response times. Nocistatin and nocistatin amide were both able to antagonize the hyperalgesic effect of nociceptin. The effect of nocistatin amide was longer lasting and more potent, suggesting that the C-terminal free carboxyl group of nocistatin is not necessary for its biological activity, and that the amide derivative may be more biologically stable.