Role of l-arginine/SNAP/NO/cGMP/KATP channel signalling pathway in antinociceptive effect of -terpineol in mice

ObjectivesThe main purpose of this study was to assess the role of l-arginine/SNAP/NO/cGMP/K-ATP channel pathway in analgesic effects of -terpineol in mice. MethodsMale NMRI mice were pretreated intraperitoneally with NO precursor (l-arginine, 100mg/kg), NO synthase inhibitor (l-NAME, 30mg/kg), NO donor (SNAP, 1mg/kg), guanylyl cyclase inhibitor (methylene blue, 20mg/kg), PDE inhibitor (sildenafil, 0.5mg/kg), K-ATP channel blocker (glibenclamide, 10mg/kg) and naloxone (2mg/kg) 20min before the administration of -terpineol. The formalin test was performed 20min after the administration of -terpineol, and nociceptive responses of mice were recorded during 30min. Key findingsA significant and dose-dependent antinociception was produced by -terpineol (40 and 80mg/kg) in both the phases of formalin test. The antinociceptive effect of -terpineol was significantly potentiated by l-arginine in the second phase while significantly antagonized by l-NAME in both phases of formalin test. Also, SNAP and sildenafil non-significantly enhancedwhile methylene blue significantly diminishedthe antinociceptive effect of -terpineol in both phases of formalin test. Glibenclamide significantly reversed the -terpineol-induced antinociception, indicating the involvement of K-ATP channels in antinociceptive effect of -terpineol. ConclusionsThese results indicate that the antinociceptive effect of -terpineol is mediated through l-arginine/SNAP/NO/cGMP/K-ATP channel pathway.