Antinociceptive effect of salvinorin A from the extract of Salvia divinorum in formalin-evoked trigeminal pain behavior in mice: Underlying mechanisms.

Ethnopharmacological Relevance: Salvia divinorum (SD) is used in the Mexican Mazatec indigenous medicine to treat several pain conditions.

Aims Of The Study: to investigate the antinociceptive effect of SD and salvinorin A (SA) in formalin-evoked trigeminal pain behavior in mice, as well as the underlying mechanism of action and neuropharmacological profile of SA.

Material And Methods: acetonic extract from dried leaves of SD (AE-SD) was obtained by maceration. SA was purified by column chromatography and recrystallization. Male ICR mice (25-30 g) were injected with 20 μl (s.c) of 2.5 % formalin, into the right upper lip. Increasing doses of AE-SD or SA were administered intraperitoneally, moreover, mice were pretreated with AM251 (1 mg/kg), AM630 (1 mg/kg), bicuculline (1 mg/kg) or capsazepine (3 mg/kg), and then administrated with SA. Open field, hole boar, rotarod, exploratory cylinder, elevated plus-maze, and forced swim tests were used to evaluate the neuropharmacological profile of SA.

Results: Increasing doses of AE-SD (3.2, 10, 32, and 100 mg/kg, i. p.) or SA (0.1, 0.32, 1 and 3.2 mg/kg, i. p.) reduced the formalin-induced face rubbing behavior in mice. The antinociceptive effect of SA was prevented by pretreatment with the antagonists AM251 and capsazepine. SA increased the immobility time in mice submitted to the forced swim test and decreased the number of rearing events in the exploratory cylinder test.

Conclusion: the findings suggest that AE-SD and SA attenuate the nociception in formalin-induced orofacial pain in mice, through activation of CB1R and TRPV1, which include depressive and sedative side-effects.