Intrathecal administration of neuronostatin induces an antinociceptive effect in a mouse visceral pain model

Neuronostatin(NST)is a peptide encoded by the somatostatin gene that serves important physiological functions in diverse tissues.Previous studies have shown that intracerebroventricular administration of NST induces antinociceptive effects and hyperalgesic effects as determined by the tail immersion assay and formalin test,respectively.In the present study,we aimed to evaluate the effects of intrathecal(i.t.)injection of NST on nociception in a model of visceral pain,and determine possible mechanisms of action in mice.NST(1,3,6,or 12 nmol)was administered to mice,leading to a dose-dependent antinociceptive effect as determined by the acetic acid-induced writhing test in mice.NST(1 nmol)also enhanced the antinociceptive effect of morphine(2.5 and 5μg/kg)in the spine.Naloxone andβ-funaltrexamine hydrochloride significantly antagonized the antinociceptive effect of NST.The expression of G-protein-coupled receptor 107(GPR107)protein and the phosphorylation of PKA at Thr197 were increased after i.t.administration of NST,suggesting that theμ-opioid receptor and GPR107/PKA signaling pathway are involved in the analgesic response.In conclusion,i.t.injection of NST may potentially be used as a new approach in the mediation of visceral pain.