Anti-allodynic effects of N-demethylsinomenine, an active metabolite of sinomenine, in a mouse model of postoperative pain

Sinomenine , a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum , has been reported to have analgesic effects in various pain animal models. N -demethylsinomenine, the N -demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum . This study examined the anti-allodynic effects of N -demethylsinomenine in a mouse model of postoperative pain . A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N -demethylsinomenine (10–40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N -demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N- demethylsinomenine was quicker than sinomenine. Repeated treatment with N- demethylsinomenine (10–40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N -demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline , a selective γ-aminobutyric acid type A (GABA A ) receptor antagonist. In addition, the doses of N -demethylsinomenine used here did not alter the locomotor activity in mice. Our findings demonstrated that N -demethylsinomenine exerts behaviorally-specific anti-allodynia against postoperative allodynia mediated through the GABA A receptors, suggesting it may be a useful novel pharmacotherapy for the control of postoperative pain.