Central administration of neuronostatin induces antinociception in mice

► I.c.v. administration of neuronostatin produced a dose- and time-related antinociceptive effect in the tail immersion assay in mice. ► Neuronostatin produces its full analgesic effect by activating μ-and κ-opioid receptors. ► The analgesic effects of neuronostatin are dependent upon the central melanocortin system ► C-terminal amidation modification of neuronostatin is essential to exert its antinociceptive effect. ► Neuronostatin (6 nmol, i.c.v.) increased c-Fos protein expression in the periaqueductal gray (PAG) and the nucleus raphe magnus (NRM).