Peripheral analgesic action of clonidine: mediation by release of endogenous enkephalin-like substances.
Clonidine analgesia was tested on the hyperalgesia induced by intraplantar injection of prostaglandin E2 or carrageenin. The antinociceptive effect of clonidine was dose-dependent and was abolished by local administration of the selective alpha 2-adrenoceptor blocker, yohimbine or of the opioid antagonists naloxone or quaternary nalorphine. St-91, a clonidine analog which does not cross the blood-brain barrier also promoted significant antinociception. Repeated administration of drugs possessing a central mechanism of analgesic action leads to the development of tolerance in this test. Significant analgesic tolerance was observed following repeated (5 days) morphine (8 mg/kg) or high doses of clonidine (0.5 mg/kg). In contrast, no tolerance was detected to the analgesic effect of low doses of clonidine (0.15 mg/kg) or of St-91 (0.5 mg/kg). These results suggest that, in addition to its central analgesic action, clonidine can induce peripheral antinociception by an alpha 2-adrenoceptor-mediated local release of enkephalin-like substances.
Nakamura
M
M
Department of Pharmacology, University of Minas Gerais, Brazil.
Ferreira
S H
SH
D000700:Analgesics; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015232:Dinoprostone; D004361:Drug Tolerance; D004745:Enkephalins / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D004745:Enkephalins; D011458:Prostaglandins E; D015016:Yohimbine; D009270:Naloxone; D009020:Morphine; D002351:Carrageenan; D015232:Dinoprostone; D003000:Clonidine