Activation of spinal nicotinic receptors evokes a prominent algogenic respo
nse. Recently, epibatidine. a potent nicotinic agonist, was found to displa
y an antinociceptive response after systemic administration. To examine the
spinal component of this: action, effects of three nicotinic agonists-epib
atidine. cytisine and nicotine-were given intrathecally (IT) and their anti
nociceptive activity was subsequently assessed. All agents elicited dose-de
pendent algogenic activity, characterized at lower doses by touch-evoked hy
peractivity and at higher doses by intermittent vocalization and marked beh
avioral activity, with the rank order of potency being epibatidine > cytisi
ne > nicotine. In addition, intrathecal epibatidine elicited a short-lastin
g, dose-dependent thermal antinociception. In contrast, the other nicotinic
agonists at the highest usable dose failed to produce a significant antino
ciception. Mecamylamine, a nicotinic channel blocker, completely abolished
the antinociceptive and algogenic responses of epibatidine. The competitive
antagonist, alpha-lobeline, blocked both the analgesic and algogenic respo
nses, but methyllycaconitine inhibited only the algogenic effects of epibat
idine. Dihydro-beta-erythroidine, also a competitive antagonist, had no eff
ect on the initial intense algogenic responses. The analgesic response to e
pibatidine was neither inhibited by naloxone not by atropine. 2-Amino-5-pho
sphopentanoic acid, a competitive N-methyl-D-aspartate receptor antagonist,
did not affect the analgesic response to intrathecal epibatidine or the in
tense initial algogenic response. Upon repeated administration (30-min inte
rval), epibatidine(1 mu g, IT exhibited marked and rapid desensitization to
both the analgesic and algogenic responses which recovered within 8 h. Pre
treatment with two consecutive doses of cytisine (5 mu g, IT, 30-min apart)
inhibited the agitation and analgesic actions of intrathecal epibatidine.
Thus, we contend that in addition to the typical nociceptive response elici
ted by spinal nicotinic agonists, intrathecal epibatidine also exhibits a p
ronounced but short-lasting antinociception. The analgesic and algogenic re
sponses to intrathecal epibatidine may be mediated by distinct subtypes of
spinal nicotinic receptors as suggested by the antagonist studies. (C) 1998
Elsevier Science Ltd. All rights reserved.