Potent antinociceptive effects of clonidine systemically administered in an experimental model of clinical pain, the arthritic rat.
The effects of various doses of the alpha-2 adrenoceptor agonist clonidine administered systemically (30, 50 and 100 micrograms/kg i.v.), were investigated on the vocalization threshold to paw pressure in normal rats and in rats with Freund's adjuvant-induced arthritis. Previous results have suggested that there is an increase in the activity of the bulbospinal noradrenergic systems in these arthritic animals. In the present study, clonidine led to significant antinociceptive effects in both groups of rats. Clonidine was found to be highly effective in arthritic animals, even at the lower concentration: the elevation in threshold produced by 30 micrograms/kg i.v. was 160% in arthritic vs. 124% in normal rats. The effects of clonidine were prevented dose-dependently by pretreatment with yohimbine or idazoxan 250 to 1000 micrograms/kg i.v., in the two groups of rats, indicating clearly that the dose-dependent effects of i.v. clonidine are mediated by alpha-2 adrenoceptors.
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U 161, Paris France.
V
V
Kayser
G
G
Guilbaud
J M
JM
Besson
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D007275:Injections, Intravenous; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000187:drug effects; D014828:Vocalization, Animal; D015016:Yohimbine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000700:Analgesics; D004146:Dioxanes; D015016:Yohimbine; D003000:Clonidine; D019329:Idazoxan