ANTINOCICEPTIVE RESPONSES TO NICOTINIC ACETYLCHOLINE-RECEPTOR LIGANDSAFTER SYSTEMIC AND INTRATHECAL ADMINISTRATION IN MICE

The objective of this study was to determine which nicotinic receptor subtypes are involved in antinociception and their site of action. For that, the antinociceptive effects of several nicotinic receptor ligan ds were evaluated in the tail-flick test both after s.c. and intrathec al (i.t.) administration. Nicotine and other nicotine agonists increas ed tail-flick latencies in a dose-dependent manner after both routes o f administration. Epibatidine enantiomers were the most potent agonist s examined. Cytisine, a potent nicotinic ligand, failed to elicit anti nociception when injected either i.t. or s.c. Despite some similaritie s in the effects of nicotinic agonists after i.t, and s.c. injections, their rank-order potency was different. In contrast to the s.c. resul ts, the stereoselectivity of nicotine's effect after i.t. administrati on was minimal. When various nicotinic antagonists were compared after i.t. and s.c. administration, the results showed that mecamylamine an d dihydro-beta-erythroidine differ in potency and their degree of anta gonism of some of the nicotinic agonists given i.t. These data suggest that different subtypes of nicotinic receptors may exist in the spina l cord. A good correlation was found between binding affinity to [H-3] -nicotine binding sites and analgesic potency after i.t. (r = 0.82), s uggesting the involvement of alpha(4) beta(2) receptor subunits. In co ntrast, studies with MLA and alpha-BGTX suggested a minimal role for a lpha-BGTX-sensitive receptors in the antinociceptive effect of nicotin ic agonists.