Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Apr;108(4):907–913. doi: 10.1111/j.1476-5381.1993.tb13485.x

The spinal antinociceptive activity of the alpha 2-adrenoceptor agonist, xylazine in sheep.

A E Kyles 1, A E Waterman 1, A Livingston 1
PMCID: PMC1908155  PMID: 8097956

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.

Full text

PDF
907

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clarke K. W., Hall L. W. "Xylazine"--a new sedative for horses and cattle. Vet Rec. 1969 Nov 8;85(19):512–517. doi: 10.1136/vr.85.19.512. [DOI] [PubMed] [Google Scholar]
  2. Duggan A. W., Morton C. R. Tonic descending inhibition and spinal nociceptive transmission. Prog Brain Res. 1988;77:193–211. doi: 10.1016/s0079-6123(08)62786-7. [DOI] [PubMed] [Google Scholar]
  3. Eisenach J. C., Dewan D. M., Rose J. C., Angelo J. M. Epidural clonidine produces antinociception, but not hypotension, in sheep. Anesthesiology. 1987 Apr;66(4):496–501. doi: 10.1097/00000542-198704000-00008. [DOI] [PubMed] [Google Scholar]
  4. Ernsberger P., Giuliano R., Willette R. N., Granata A. R., Reis D. J. Hypotensive action of clonidine analogues correlates with binding affinity at imidazole and not alpha-2-adrenergic receptors in the rostral ventrolateral medulla. J Hypertens Suppl. 1988 Dec;6(4):S554–S557. doi: 10.1097/00004872-198812040-00174. [DOI] [PubMed] [Google Scholar]
  5. Ferreira S. H. Peripheral analgesia: mechanism of the analgesic action of aspirin-like drugs and opiate-antagonists. Br J Clin Pharmacol. 1980 Oct;10 (Suppl 2):237S–245S. doi: 10.1111/j.1365-2125.1980.tb01806.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fisher B., Zornow M. H., Yaksh T. L., Peterson B. M. Antinociceptive properties of intrathecal dexmedetomidine in rats. Eur J Pharmacol. 1991 Jan 10;192(2):221–225. doi: 10.1016/0014-2999(91)90046-s. [DOI] [PubMed] [Google Scholar]
  7. Fujimoto J. M., Arts K. S. Clonidine, administered intracerebroventricularly in mice, produces an anti-analgesic effect which may be mediated spinally by dynorphin A (1-17). Neuropharmacology. 1990 Apr;29(4):351–358. doi: 10.1016/0028-3908(90)90093-7. [DOI] [PubMed] [Google Scholar]
  8. Headley P. M., Duggan A. W., Griersmith B. T. Selective reduction by noradrenaline and 5-hydroxytryptamine of nociceptive responses of cat dorsal horn neurones. Brain Res. 1978 Apr 21;145(1):185–189. doi: 10.1016/0006-8993(78)90809-0. [DOI] [PubMed] [Google Scholar]
  9. Howe J. R., Yaksh T. L. Changes in sensitivity to intrathecal norepinephrine and serotonin after 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) or repeated monoamine administration. J Pharmacol Exp Ther. 1982 Feb;220(2):311–321. [PubMed] [Google Scholar]
  10. Kalso E. A., Pöyhiä R., Rosenberg P. H. Spinal antinociception by dexmedetomidine, a highly selective alpha 2-adrenergic agonist. Pharmacol Toxicol. 1991 Feb;68(2):140–143. doi: 10.1111/j.1600-0773.1991.tb02052.x. [DOI] [PubMed] [Google Scholar]
  11. Kuraishi Y., Harada Y., Takagi H. Noradrenaline regulation of pain-transmission in the spinal cord mediated by alpha-adrenoceptors. Brain Res. 1979 Oct 5;174(2):333–336. doi: 10.1016/0006-8993(79)90857-6. [DOI] [PubMed] [Google Scholar]
  12. Kyles A. E., Waterman A., Livingston A. Chronic intrathecal catheterization in the sheep. J Pharmacol Toxicol Methods. 1992 May;27(3):177–183. doi: 10.1016/1056-8719(92)90038-3. [DOI] [PubMed] [Google Scholar]
  13. Ley S., Waterman A., Livingston A. Variation in the analgesic effects of xylazine in different breeds of sheep. Vet Rec. 1990 May 19;126(20):508–508. [PubMed] [Google Scholar]
  14. Lipman J. J., Spencer P. S. Further evidence for a central site of action for the antinociceptive effect of clonidine-like drugs. Neuropharmacology. 1979 Aug-Sep;18(8-9):731–733. doi: 10.1016/0028-3908(79)90045-5. [DOI] [PubMed] [Google Scholar]
  15. Michel M. C., Insel P. A. Are there multiple imidazoline binding sites? Trends Pharmacol Sci. 1989 Sep;10(9):342–344. doi: 10.1016/0165-6147(89)90002-3. [DOI] [PubMed] [Google Scholar]
  16. Murata K., Nakagawa I., Kumeta Y., Kitahata L. M., Collins J. G. Intrathecal clonidine suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats. Anesth Analg. 1989 Aug;69(2):185–191. [PubMed] [Google Scholar]
  17. Ness T. J., Gebhart G. F. Differential effects of morphine and clonidine on visceral and cutaneous spinal nociceptive transmission in the rat. J Neurophysiol. 1989 Jul;62(1):220–230. doi: 10.1152/jn.1989.62.1.220. [DOI] [PubMed] [Google Scholar]
  18. Nolan A., Livingston A., Morris R., Waterman A. Techniques for comparison of thermal and mechanical nociceptive stimuli in the sheep. J Pharmacol Methods. 1987 Mar;17(1):39–49. doi: 10.1016/0160-5402(87)90035-0. [DOI] [PubMed] [Google Scholar]
  19. Nolan A., Livingston A., Waterman A. Antinociceptive actions of intravenous alpha 2-adrenoceptor agonists in sheep. J Vet Pharmacol Ther. 1987 Sep;10(3):202–209. doi: 10.1111/j.1365-2885.1987.tb00530.x. [DOI] [PubMed] [Google Scholar]
  20. Ossipov M. H., Suarez L. J., Spaulding T. C. A comparison of the antinociceptive and behavioral effects of intrathecally administered opiates, alpha-2-adrenergic agonists, and local anesthetics in mice and rats. Anesth Analg. 1988 Jul;67(7):616–624. [PubMed] [Google Scholar]
  21. Paalzow L. Analgesia produced by clonidine in mice and rats. J Pharm Pharmacol. 1974 May;26(5):361–363. doi: 10.1111/j.2042-7158.1974.tb09291.x. [DOI] [PubMed] [Google Scholar]
  22. Post C., Gordh T., Jr, Minor B. G., Archer T., Freedman J. Antinociceptive effects and spinal cord tissue concentrations after intrathecal injection of guanfacine or clonidine into rats. Anesth Analg. 1987 Apr;66(4):317–324. [PubMed] [Google Scholar]
  23. Raptopoulos D., Weaver B. M. Observations following intravenous xylazine administration in steers. Vet Rec. 1984 Jun 9;114(23):567–569. doi: 10.1136/vr.114.23.567. [DOI] [PubMed] [Google Scholar]
  24. Reddy S. V., Yaksh T. L. Spinal noradrenergic terminal system mediates antinociception. Brain Res. 1980 May 12;189(2):391–401. doi: 10.1016/0006-8993(80)90099-2. [DOI] [PubMed] [Google Scholar]
  25. Sagen J., Proudfit H. K. Effect of intrathecally administered noradrenergic antagonists on nociception in the rat. Brain Res. 1984 Sep 24;310(2):295–301. doi: 10.1016/0006-8993(84)90152-5. [DOI] [PubMed] [Google Scholar]
  26. Schmitt H., Le Douarec J. C., Petillot N. Antinociceptive effects of some alpha-sympathomimetic agents. Neuropharmacology. 1974 May;13(5):289–294. doi: 10.1016/0028-3908(74)90112-9. [DOI] [PubMed] [Google Scholar]
  27. Spaulding T. C., Venafro J. J., Ma M. G., Fielding S. The dissociation of the antinociceptive effect of clonidine from supraspinal structures. Neuropharmacology. 1979 Jan;18(1):103–105. doi: 10.1016/0028-3908(79)90015-7. [DOI] [PubMed] [Google Scholar]
  28. Sullivan A. F., Dashwood M. R., Dickenson A. H. Alpha 2-adrenoceptor modulation of nociception in rat spinal cord: location, effects and interactions with morphine. Eur J Pharmacol. 1987 Jun 19;138(2):169–177. doi: 10.1016/0014-2999(87)90430-4. [DOI] [PubMed] [Google Scholar]
  29. Tibiriça E., Feldman J., Mermet C., Gonon F., Bousquet P. An imidazoline-specific mechanism for the hypotensive effect of clonidine: a study with yohimbine and idazoxan. J Pharmacol Exp Ther. 1991 Feb;256(2):606–613. [PubMed] [Google Scholar]
  30. Waterman A., Livingston A., Bouchenafa O. Analgesic effects of intrathecally-applied alpha 2-adrenoceptor agonists in conscious, unrestrained sheep. Neuropharmacology. 1988 Feb;27(2):213–216. doi: 10.1016/0028-3908(88)90173-6. [DOI] [PubMed] [Google Scholar]
  31. Yaksh T. L., Reddy S. V. Studies in the primate on the analgetic effects associated with intrathecal actions of opiates, alpha-adrenergic agonists and baclofen. Anesthesiology. 1981 Jun;54(6):451–467. doi: 10.1097/00000542-198106000-00004. [DOI] [PubMed] [Google Scholar]
  32. Zemlan F. P., Corrigan S. A., Pfaff D. W. Noradrenergic and serotonergic mediation of spinal analgesia mechanisms. Eur J Pharmacol. 1980 Jan 25;61(2):111–124. doi: 10.1016/0014-2999(80)90154-5. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES