Objective To investigate the
analgesia induced by
cobrotoxin (CT) from
venom of Naja naja atra, and the effects of
atropine and
naloxone on the antinociceptive activity of CT in rodent
pain models. Methods CT was administered intraperitoneally (33.3, 50, 75 mu g/kg), intra-cerebral venticularly (2.4 mu g/kg) or microinjected into periaqueductal gray (PAG, 1.2 mu g/kg). The antinoCiceptive action was tested using the hot-plate test and the
acetic acid writhing test in mice and rats. The involvement of
cholinergic system and the
opioid system in CT-induced
analgesia was examined by pretreatment of animals with
atropine (0.5 mg/kg, im or 10 mg/kg, ip) or
naloxone (3 mg/kg, ip). The effect of CT on motor activity was tested using the Animex test. Results CT (33.3, 50 and 75 mu g/kg, ip) exhibited a dosedependent
analgesic action in mice as determined with hot-plate test and
acetic acid writhing test. In the mouse
acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 mu g/kg (1/23th of a systemic dose) produced marked
analgesic effects. Microinjection of CT 1.2 mu g/kg (1/46th of systemic dose) into the PAG also elicited a robust
analgesic action in the hot-plate test in rats.
Atropine at 0.5 mg/kg (im) or
naloxone at 3 mg/kg (ip) failed to block the
analgesic effects of CT, but
atropine at 10 mg/kg (ip) did antagonize the
analgesia mediated by CT in the mouse
acetic acid writhing test. At the highest effective dose of antinociception (75 mu g/kg), CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra
venom has
analgesic effects. Central nervous system may be involved in CT's
analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central
cholinergic system but not
opioid system appears to be involved in the antinociceptive action of CT.