Molecular Mechanism for Analgesia Involving Specific Antagonism of α9α10 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, J. Michael
• Format: Article
• Language: English
• Subjects: Analgesia; Analgesics; Biological Sciences; Cholinergic receptors; Lymphocytes; Macrophages; Nerves; Nervous system trauma; Pain; Peripheral nervous system diseases; Sciatic nerve
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0608715103

α9α10 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 α9α10 nAChRs is not known. Here we show that selective block (rather than stimulation) of α9α10 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 α9α10 nAChRs in the pathophysiology of peripheral nerve injury.