Nicotinic acetylcholine receptors expressed in the ventralposterolateral thalamic nucleus play an important role in anti-allodynic effects.
OBJECTIVE
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 [(125)I]5IA.


METHODS
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 [(125)I]5IA autoradiography and the involvement of nACh receptors in anti-nociceptive effects in the region where changes occurred.


RESULTS
Autoradiographic studies showed that the accumulation of [(125)I]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
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.
Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
M
M
Ueda
Y
Y
Iida
A
A
Tominaga
T
T
Yoneyama
M
M
Ogawa
Y
Y
Magata
H
H
Nishimura
Y
Y
Kuge
H
H
Saji
D000818:Animals; D001345:Autoradiography; D001384:Azetidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007457:Iodine Radioisotopes; D008297:Male; D018722:Nicotinic Agonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D017288:Pain Threshold; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000502:physiology; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism; D020651:Ventral Thalamic Nuclei / Q000187:drug effects* / Q000378:metabolism
C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic