PT - JOURNAL ARTICLE AU - M. I. Damaj AU - M. Fei-Yin AU - M. Dukat AU - W. Glassco AU - R. A. Glennon AU - B. R. Martin TI - Antinociceptive Responses to Nicotinic Acetylcholine Receptor Ligands after Systemic and Intrathecal Administration in Mice DP - 1998 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1058--1065 VI - 284 IP - 3 4099 - http://jpet.aspetjournals.org/content/284/3/1058.short 4100 - http://jpet.aspetjournals.org/content/284/3/1058.full SO - J Pharmacol Exp Ther1998 Mar 01; 284 AB - 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 ligands were evaluated in the tail-flick test both after s.c. and intrathecal (i.t.) administration. Nicotine and other nicotine agonists increased tail-flick latencies in a dose-dependent manner after both routes of administration. Epibatidine enantiomers were the most potent agonists examined. Cytisine, a potent nicotinic ligand, failed to elicit antinociception when injected either i.t. or s.c. Despite some similarities 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. results, the stereoselectivity of nicotine’s effect after i.t. administration was minimal. When various nicotinic antagonists were compared after i.t. and s.c. administration, the results showed that mecamylamine and dihydro-β-erythroidine differ in potency and their degree of antagonism of some of the nicotinic agonists given i.t. These data suggest that different subtypes of nicotinic receptors may exist in the spinal cord. A good correlation was found between binding affinity to [3H]-nicotine binding sites and analgesic potency after i.t. (r = 0.82), suggesting the involvement of α4β2 receptor subunits. In contrast, studies with MLA and α-BGTX suggested a minimal role for α-BGTXsensitive receptors in the antinociceptive effect of nicotinic agonists. The American Society for Pharmacology and Experimental Therapeutics