Nicotinic acetylcholine receptors expressed in the ventralposterolateral thalamic nucleus play an important role in anti-allodynic effects

M. Ueda, Y. Iida, A. Tominaga, T. Yoneyama, M. Ogawa, Y. Magata, H. Nishimura, Y. Kuge, H. Saji

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1201-1210
Number of pages10
JournalBritish Journal of Pharmacology
Volume159
Issue number6
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

Keywords

  • 5IA
  • Anti-allodynic effect
  • Neuropathic pain
  • Nicotinic acetylcholine receptor
  • Thalamus
  • Ventral posterolateral thalamic nucleus

ASJC Scopus subject areas

  • Pharmacology

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