title: The spinal antinociceptive activity of the alpha 2-adrenoceptor agonist, xylazine in sheep.
abstract: 1. The intrathecal administration of xylazine (100 micrograms), 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 alpha 2-adrenoceptor antagonist, idazoxan. 2. The intrathecal administration of the selective alpha 2-antagonists, idazoxan (100 micrograms) and RX811059 (33 micrograms), 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. 3. Examination of the distribution of tritiated idazoxan (25 microCi in 100 microliters) indicated that the site of action of the drug was limited to the cervical spinal cord after intrathecal administration. 4. These studies demonstrate that a significant proportion of the antinociceptive effect of systemically administered xylazine is mediated by spinal alpha 2-adrenoceptors.
authors.affiliation: Department of Veterinary Surgery, University of Bristol, Langford.
authors.forename: A E
authors.initials: AE
authors.lastname: Kyles
authors.forename: A E
authors.initials: AE
authors.lastname: Waterman
authors.forename: A
authors.initials: A
authors.lastname: Livingston
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D019329:Idazoxan / Q000031:analogs & derivatives; D007275:Injections, Intravenous; D007278:Injections, Spinal; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D012756:Sheep; D013116:Spinal Cord / Q000187:drug effects*; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D004146:Dioxanes; D014991:Xylazine; C065483:ethoxyidazoxan; D019329:Idazoxan