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 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.
Vincler
Michelle
M
Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Wittenauer
Shannon
S
Parker
Renee
R
Ellison
Michael
M
Olivera
Baldomero M
BM
McIntosh
J Michael
JM
D000698:Analgesia; D000700:Analgesics / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D020916:Conotoxins / Q000378:metabolism / Q000627:therapeutic use; D004594:Electrophysiology; D006801:Humans; D008297:Male; D018733:Nicotinic Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology
D000700:Analgesics; C470699:Chrna10 protein, rat; C498541:Chrna9 protein, rat; D020916:Conotoxins; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C510079:conotoxin alpha-RgIA, Conus regius; C507383:alpha-conotoxin Vc1.1