Nocistatin is a biologically active peptide derived from prepronociceptin, and its intrathecal administration has been reported to reduce nociceptin- or prostaglandin E2-induced hyperalgesia and allodynia in mice. In this study, we investigated the effects of intracerebroventricular (i.c.v.) administration of nocistatin on the inflammatory hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin in the rat paw-pressure test. Intracerebroventricular administration of nocistatin (0.5-50 pmol/rat) dose-dependently reduced carrageenan/kaolin-induced hyperalgesia, which peaked at 15-30 m. However, i.c.v. administration of nocistatin (50 pmol/rat) had no effect on the nociceptive threshold of non-inflamed rats. These results indicate that nocistatin has anti-hyperalgesic effects on the inflammatory hyperalgesia induced by carrageenan/kaolin at the supraspinal level.