The activation of
cholinergic pathways by
nicotine elicits various physiological and pharmacological effects in mammals. For example, the stimulation of
nicotinic acetylcholine receptors (nAChRs) leads to an antinociceptive effect. However, it remains to be elucidated which subtypes of nAChR are involved in the antinociceptive effect of
nicotine on nerve injury-induced
allodynia and the underlying cascades of the nAChR-mediated antiallodynic effect. In this study, we attempted to characterize the actions of
nicotine at the spinal level against
mechanical allodynia in an animal model of
neuropathic pain, tibial nerve transection (
TNT) in rats. It was found that the
intrathecal injection of
nicotine,
RJR-2403, a selective alpha4beta2 nAChR agonist, and
choline, a selective alpha7 nAChR agonist, produced an antinociceptive effect on the
TNT-induced
allodynia. The actions of
nicotine were almost completely suppressed by pretreatment with
mecamylamine, a non-selective nicotinic antagonist, or
dihydro-beta-erythroidine, a selective alpha4beta2 nAChR antagonist, and partially reversed by pretreatment with
methyllycaconitine, a selective alpha7 nAChR antagonist. Furthermore, pretreatment with
strychnine, a
glycine receptor antagonist, blocked the antinociception induced by
nicotine,
RJR-2403, and
choline. On the other hand, the GABAA antagonist
bicuculline did not reverse the antiallodynic effect of
nicotine. Together, these results indicate that the alpha4beta2 and alpha7 nAChR system, by enhancing the activities of glycinergic neurons at the spinal level, exerts a suppressive effect on the nociceptive transduction in
neuropathic pain.