The influence of the time course of inflammation and spinalization on the antinociceptive activity of the alpha2-adrenoceptor agonist medetomidine.
The purpose of the present study was to investigate the influence of the time course of inflammation and the implication of spinal and supraspinal sites on the antihyperalgesic effects of the alpha(2)-adrenoceptor agonist medetomidine. Behavioral experiments showed a more intense antihyperalgesia in the phase of maintenance of inflammation than in the early or resolution stages. Maximum effect, without sedation, was observed with a dose of 40 microg/kg (66+/-12% and 76+/-15% reduction of mechanical and thermal hyperalgesia). No change was observed in the paw swelling, indicating that its effects were not secondary to a reduction of inflammation. In electrophysiological experiments, the effect was more pronounced in animals with an intact spinal cord than in spinalized animals (max. effects of 2+/-0.7% vs. 48+/-11% of control, noxious mechanical stimulation). We conclude that the antihyperalgesic effect of medetomidine depends on the time course of inflammation and that it is mainly located supraspinally.
Departamento de Fisiología, Facultad de Medicina, Campus Universitario, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Carlos
C
Molina
Juan F
JF
Herrero
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006614:Hindlimb / Q000187:drug effects / Q000294:innervation; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008297:Male; D020926:Medetomidine / Q000494:pharmacology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D018341:Receptors, Adrenergic, alpha-2; D002351:Carrageenan; D020926:Medetomidine