The periaqueductal gray is the site of the antinociceptive action of carbamazepine as related to bradykinin-induced trigeminal pain.

Using freely moving and conscious rats, the antinociceptive effects of microinjections of carbamazepine, into the periaqueductal gray (PAG), nucleus reticularis paragigantocellularis (NRPG) and nucleus raphé magnus (NRM) on the biting-like responses induced by bradykinin applied to the tooth pulp, were investigated to determine the primary site of action of this drug. Microinjections of carbamazepine into the PAG ipsi- and contralateral to the stimulated tooth pulp produced dose-dependent suppressive effects on the biting-like responses within 1 min. The ED50 was 1.57 micrograms per rat, that is about 1,500 times less than that for carbamazepine administered systemically. The antinociceptive effect of carbamazepine administered into the PAG was inhibited by pretreatment with bicuculline but not by phentolamine, propranolol and haloperidol. Microinjections of carbamazepine into the NRPG and NRM were rarely effective in the production of antinociception at doses used (up to 3 micrograms per rat). These results suggest that the PAG is one of the primary target sites for the antinociceptive activity of carbamazepine, and that GABAergic systems are involved this action of carbamazepine.