Molecular mechanism for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors

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 a9a10 nAChRs in the pathophysiology of peripheral nerve injury.