Molecular mechanism for analgesia involving specific antagonism of alpha 9 alpha 10 nicotinic acetylcholine receptors

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (47), p.17880-17884
• Main Authors: Vincler, Michelle, Wittenauer, Shannon, Parker, Renee, Ellison, Michael, Olivera, Baldomero M, McIntosh, JMichael
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0608715103

alpha 9 alpha 10 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 alpha 9 alpha 10 nAChRs is not known. Here we show that selective block (rather than stimulation) of alpha 9 alpha 10 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 alpha 9 alpha 10 nAChRs in the pathophysiology of peripheral nerve injury.