title: A role for endothelin in neuropathic pain after chronic constriction injury of the sciatic nerve.
abstract: The purpose of this study was to explore the role of endothelin in neuropathic pain. Endothelins (ET) are a family (ET-1, ET-2, ET-3) of ubiquitously expressed peptides involved in control of vascular tone. Injected ET-1 causes intense pain via activation of ETA receptors, modulated by analgesic signals initiated by ETB receptor activation. Using a rat model of chronic constriction injury of the sciatic nerve, we found that pharmacologic ETA receptor antagonism acutely and significantly reduced thermal and mechanical hyperalgesic responses 5 days after injury. Furthermore, ET-1 and the ETA receptor are locally upregulated at the site of chronic constriction injury at both the message and the protein levels, suggesting that ET-1 may be involved in establishing pain after the injury. These data point to ET-1 as an important mediator of pain in general and suggest that ETA antagonism deserves study as a potential novel therapy for neuropathic pain.
authors.affiliation: Departments of Anesthesiology and Cell Biology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Markus
authors.initials: M
authors.lastname: Klass
authors.forename: Allen
authors.initials: A
authors.lastname: Hord
authors.forename: Melissa
authors.initials: M
authors.lastname: Wilcox
authors.forename: Don
authors.initials: D
authors.lastname: Denson
authors.forename: Marie
authors.initials: M
authors.lastname: Csete
mesh_terms: D000818:Animals; D003251:Constriction, Pathologic; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology; D020426:Sciatic Neuropathy / Q000150:complications*
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A