Mechanisms involved in the antinociception caused by melatonin in mice (original) (raw)

2006, Journal of Pineal Research

The pregnane compound MV8612 isolated from the rhizome of the plant Mandevilla velutina administered by intraperitoneal (i.p.), intrathecal (i.t.) or by intracerebroventricular (i.c.v.) routes caused graded and complete inhibition of the thermal hyperalgesia caused by i.t. injection of bradykinin (BK) in mice with mean ID values of 7.8 mmol / kg, 33.6 and 4.6 nmol / site, respectively. Compound 50 MV8612 (i.p.) also inhibited both the neurogenic and inflammatory pain responses to formalin with mean ID values of 5.6 and 10.6 50 mmol / kg, respectively. Given i.t., MV8612 produced significant inhibition of both phases of the formalin-induced licking (inhibition of 3465 and 3664%, respectively). Given by i.c.v. route MV8612 inhibited both phases of formalin-induced pain (3266 and 6365%) with mean ID of 8.4 nmol / site against the late phase. MV8612, given by i.p., i.c.v. or i.t. routes, also inhibited capsaicin-induced pain 50 1 (5164, 2568 and 3966%, respectively). The i.t. injection of potassium (K ) channel blockers, apamin and charybdotoxin given 15 min before, markedly prevented the antinociception of MV8612 against both phases of formalin-induced nociception. In contrast, tetraethylammonium (TEA) or glibenclamide had no effect. The i.c.v. treatment with pertussis toxin resulted in a significant inhibition of both MV8612-and morphine-induced antinociception against both phases of formalin-induced pain. Taken together these results confirm and also extend our previous data by demonstrating that the greater part of the antinociception caused by MV8612 seems to be associated 21 1