The influence of the time course of inflammation and spinalization on the antinociceptive activity of the α2-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 α2-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 μg/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.