Possible involvement of the μ opioid receptor in the antinociception induced by sinomenine on formalin-induced nociceptive behavior in mice

Sinomenine, an alkaloid originally isolated from the roots and the rhizome of Sinomenium acutum is used as a traditional Chinese herbal medicines for rheumatoid arthritis and neuralgia. The aims of this study were to investigate the effects of oral administration of shinomenine on formalin-induced nociceptive behavior in mice and the opioid receptor subtypes involved in the antinociceptive effects of sinomenine. Our findings showed that a single dose of oral-administrated sinomenine inhibited the formalin induced licking and biting responses in a dose-dependent manner. Intraperitoneal pretreatment with naloxone hydrochloride, an opioid receptor antagonist, and beta-funaltrexamine hydrochloride (beta-FNA), a selective kappa-opioid receptor antagonist, significantly attenuated sinomenine induced antinociception, but not by naltrindole, a nonselective delta-opioid receptor antagonist and nor-binaltorphimine, a selective kappa-opioid receptor antagonist. Furthermore, in western blot analysis, oral administration of sinomenine resulted in a significant blockage of spinal extracellular signal-regulated protein kinase (ERK1/2) activation induced by formalin. Naloxone hydrochloride and beta-FNA significantly reversed the blockage of spinal ERK1/2 activation induced by sinomenine. These results suggest that sinomenineinduced anti nociceptive effect and blockage of spinal ERK1/2 activation may be triggered by activation of popioid receptors.