Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors

alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of alpha9alpha10 nAChRs is not known. Here we show that selective block (rather than stimulatio...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (47), p.17880
Main Authors: Vincler, Michelle, Wittenauer, Shannon, Parker, Renee, Ellison, Michael, Olivera, Baldomero M, McIntosh, J Michael
Format: Article
Language:English
Subjects:
Analgesia
Analgesics - metabolism
Analgesics - therapeutic use
Animals
Behavior, Animal - physiology
Conotoxins - metabolism
Conotoxins - therapeutic use
Electrophysiology
Humans
Male
Nicotinic Antagonists - metabolism
Nicotinic Antagonists - therapeutic use
Pain - drug therapy
Protein Subunits - genetics
Protein Subunits - metabolism
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic - genetics
Receptors, Nicotinic - metabolism
Sciatic Nerve - metabolism
Sciatic Nerve - pathology
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Summary:alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of alpha9alpha10 nAChRs is not known. Here we show that selective block (rather than stimulation) of alpha9alpha10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of alpha9alpha10 nAChRs in the pathophysiology of peripheral nerve injury.
ISSN:0027-8424