OBJECTIVES: The main purpose of this study was to assess the role of l-arginine/SNAP/NO/cGMP/KATP channel pathway in analgesic effects of α-terpineol in mice. METHODS: Male NMRI mice were pretreated intraperitoneally with NO precursor (l-arginine, 100 mg/kg), NO synthase inhibitor (l-NAME, 30 mg/kg), NO donor (SNAP, 1 mg/kg), guanylyl cyclase inhibitor (methylene blue, 20 mg/kg), PDE inhibitor (sildenafil, 0.5 mg/kg), KATP channel blocker (glibenclamide, 10 mg/kg) and naloxone (2 mg/kg) 20 min before the administration of α-terpineol. The formalin test was performed 20 min after the administration of α-terpineol, and nociceptive responses of mice were recorded during 30 min. KEY FINDINGS: A significant and dose-dependent antinociception was produced by α-terpineol (40 and 80 mg/kg) in both the phases of formalin test. The antinociceptive effect of α-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 enhanced-while methylene blue significantly diminished-the antinociceptive effect of α-terpineol in both phases of formalin test. Glibenclamide significantly reversed the α-terpineol-induced antinociception, indicating the involvement of KATP channels in antinociceptive effect of α-terpineol. CONCLUSIONS: These results indicate that the antinociceptive effect of α-terpineol is mediated through l-arginine/SNAP/NO/cGMP/KATP channel pathway.
OBJECTIVES: The main purpose of this study was to assess the role of l-arginine/SNAP/NO/cGMP/KATP channel pathway in analgesic effects of α-terpineol in mice. METHODS: Male NMRI mice were pretreated intraperitoneally with NO precursor (l-arginine, 100 mg/kg), NO synthase inhibitor (l-NAME, 30 mg/kg), NO donor (SNAP, 1 mg/kg), guanylyl cyclase inhibitor (methylene blue, 20 mg/kg), PDE inhibitor (sildenafil, 0.5 mg/kg), KATP channel blocker (glibenclamide, 10 mg/kg) and naloxone (2 mg/kg) 20 min before the administration of α-terpineol. The formalin test was performed 20 min after the administration of α-terpineol, and nociceptive responses of mice were recorded during 30 min. KEY FINDINGS: A significant and dose-dependent antinociception was produced by α-terpineol (40 and 80 mg/kg) in both the phases of formalin test. The antinociceptive effect of α-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 enhanced-while methylene blue significantly diminished-the antinociceptive effect of α-terpineol in both phases of formalin test. Glibenclamide significantly reversed the α-terpineol-induced antinociception, indicating the involvement of KATP channels in antinociceptive effect of α-terpineol. CONCLUSIONS: These results indicate that the antinociceptive effect of α-terpineol is mediated through l-arginine/SNAP/NO/cGMP/KATP channel pathway.
Authors: Graziela Vieira; Juliana Cavalli; Elaine C D Gonçalves; Saulo F P Braga; Rafaela S Ferreira; Adair R S Santos; Maíra Cola; Nádia R B Raposo; Raffaele Capasso; Rafael C Dutra Journal: Biomolecules Date: 2020-05-20