Spinal administration of adrenergic agents produces analgesia in amphibians

• Published in: European journal of pharmacology 1996-12, Vol.316 (2), p.205-210
• Main Authors: Stevens, Craig W., Brenner, George M.
• Format: Article
• Language: English
• Subjects: Amphibian; Analgesia; Analgesics; Analgesics, Non-Narcotic - pharmacology; Animals; Biological and medical sciences; Clonidine - pharmacology; Epinephrine - pharmacology; Imidazoles - pharmacology; Injections, Spinal; Medetomidine; Medical sciences; Neuropharmacology; Norepinephrine - pharmacology; Pain; Pain - drug therapy; Pharmacology. Drug treatments; Rana esculenta; α2-Adrenoceptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00681-4

Direct intraspinal injection of the catecholamines epinephrine and norepinephrine, and the α-adrenergic agents dexmedetomidine and clonidine, produced a dose-dependent elevation of pain thresholds in the Northern grass frog, Rana pipiens. Significant analgesic effects were noted for at least 4 h. The analgesic effect of intraspinal dexmedetomidine or epinephrine was blocked by systemic pretreatment with the α 2-adrenoceptor antagonists, yohimbine and atipamezole, but not with the α 1-adrenoceptor antagonist, prazosin. Dose-response analyses showed that dexmedetomidine, epinephrine, norepinephrine had similar analgesic potencies, but clonidine was significantly less potent. Analgesia was observed without accompanying motor or sedative effects. These results suggest that α 2-adrenoceptor mechanisms which mediate analgesia may have evolved early in vertebrate evolution and that descending epinephrine-containing fibers in the amphibian nervous system may be the source of endogenous catecholamines regulating nociceptive sensitivity in the amphibian spinal cord.