title: Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat.
abstract: Vagal afferent activity modulates mechanical nociceptive threshold and inflammatory mediator-induced hyperalgesia, effects that are mediated by the adrenal medulla. To evaluate the role of epinephrine, the major hormone released from the adrenal medulla, the beta2-adrenergic receptor antagonist ICI 118,551 was chronically administered to vagotomized rats and epinephrine to normal rats. In vagotomized rats, chronic administration of ICI 118,551 markedly attenuated vagotomy-induced enhancement of bradykinin hyperalgesia but had no effect on nociceptive threshold. In normal rats, chronic epinephrine had the opposite effect, enhancing bradykinin hyperalgesia. Like vagotomy-, epinephrine-induced enhancement of hyperalgesia developed slowly, taking 14 days to reach its peak. Vagotomy induced a chronic elevation in plasma concentrations of epinephrine. We suggest that ongoing activity in vagal afferents inhibits the release of epinephrine from the adrenal medulla. Chronically elevated levels of epinephrine, occurring after vagotomy, desensitize peripheral beta2-adrenergic receptors and lead to enhancement of bradykinin hyperalgesia. The ability of prolonged elevated plasma levels of epinephrine to sensitize bradykinin receptors could contribute to chronic generalized pain syndromes.
authors.affiliation: Department of Medicine, University of California at San Francisco, CA 94143-0440, USA.
authors.forename: Sachia G
authors.initials: SG
authors.lastname: Khasar
authors.forename: Paul G
authors.initials: PG
authors.lastname: Green
authors.forename: Frederick J-P
authors.initials: FJ
authors.lastname: Miao
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D001920:Bradykinin; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000503:physiopathology*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C026777:ICI 118551; D011433:Propranolol; D001920:Bradykinin; D004837:Epinephrine