Effects Of Neuronostatin On Morphine Analgesia And Formalin Inflammatory Pain

Neuronostatin, a newly identified peptide encoded by the somatostatin (SST) gene, was proved to produce significant antinociceptive effect in mouse tail immersion test. However, the effects of neuronostatin on tonic pain and the direct functional interaction between morphine and neuronostatin havenot been characterized. In the present study, we found that intracerebroventricular (i.c.v.) administration of neuronostatin (1,3,6,12nmol/mouse) increased licking in a dose-related manner during the late phase, but did not affect the early phase of formalin test in mice. In addition, the hyperalgesic effect during the late phase was completely reversed by melanocortin3/4receptor antagonist SHU9119(50pmol/mouse) or opioid receptor antagonist naloxone (5nmol/mouse), but not GABAA receptor antagonist bicuculline (1086pmol/mouse). Also our findings showed that i.c.v. administration of neuronostatin (0.3nmol/mouse, i.c.v.) significantly enhanced the antinociceptive effect of morphine (2.5,5or10μg/kg) at the supraspinal level. Results of antagonism experiments suggested that the synergistic analgesia induced by morphine and neuronostatin was mediated by μ-and k-opioid receptors not S-opioid receptor. These may be a cascade amplification phenomenon when morphine and neuronostatin were co-administered in acute pain model. These data suggested that the hyperalgesic response induced by neuronostatin was dependent upon the central melanocortin system and endogenous opioid system. In conclusion, these results indicated that neuronostatin may be a new neuropeptide with important role in the modulation of acute and tonic pain.