Background and purpose: Much interest is currently being focused on the anti‐nociceptive effects mediated by nicotinic acetylcholine (nACh) receptors, including their location and mechanism of action. The purpose of this study was to elucidate these issues using 5‐iodo‐3‐(2(S)‐azetidinylmethoxy)pyridine (5IA), a nACh receptor agonist, and [125I]5IA.Experimental approach: We partially ligated the sciatic nerve of Sprague‐Dawley rat to induce neuropathic pain [Seltzer's partial sciatic nerve ligation (PSL) model]. We then examined the changes in nACh receptor density in the CNS using [125I]5IA autoradiography and the involvement of nACh receptors in anti‐nociceptive effects in the region where changes occurred.Key results: Autoradiographic studies showed that the accumulation of [125I]5IA and the number of nACh receptors in the thalamus of PSL rats were increased about twofold compared with those in the sham‐operated rats. No change was observed in other brain regions. Rats injected in the ventral posterolateral thalamic nucleus (VPL) with 5IA demonstrated a significant and dose‐dependent anti‐allodynic effect and this effect was completely antagonized by mecamylamine, injected with 5IA, into the VPL. The blockade of nACh receptors in the VPL by mecamylamine decreased by 70% the anti‐allodynic effect of 5IA, given i.c.v. Moreover, mecamylamine given intra‐VPL by itself, induced significant hyperalgesia.Conclusions and implications: Our findings suggest that the nACh receptors expressed in the VPL play an important role in the anti‐allodynic effects produced by exogenous and endogenous agonists.