The spinal antinociceptive activity of the α2‐adrenoceptor agonist, xylazine in sheep

Abstract

The intrathecal administration of xylazine (100 μg), via a chronic indwelling, cervical intrathecal catheter, produced a marked elevation of the mechanical nociceptive thresholds in the sheep. This antinociceptive effect was abolished by the prior intrathecal administration of the α2‐adrenoceptor antagonist, idazoxan. The intrathecal administration of the selective α2‐antagonists, idazoxan (100 μg) and RX811059 (33 μg), significantly attenuated the antinociceptive activity of intravenous xylazine, with a 60–65% reduction in the area under the antinociceptive curve. The intrathecal administration of the antagonists alone had no significant effect on nociceptive thresholds. Examination of the distribution of tritiated idazoxan (25 μCi in 100 μl) indicated that the site of action of the drug was limited to the cervical spinal cord after intrathecal administration. These studies demonstrate that a significant proportion of the antinociceptive effect of systemically administered xylazine is mediated by spinal α2‐adrenoceptors. 1993 British Pharmacological Society