A comparison of the antinociceptive effects of xylazine, detomidine and romifidine on experimental pain in horses.
OBJECTIVE
To study the analgesic potency of the alpha2-agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation.


METHODS
Randomized, placebo-controlled, blinded cross-over study.


METHODS
Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6-15 years.


METHODS
Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pneumatically operated pin pressing on the cannon bone. Measurements were made immediately before and every 15 minutes for 2 hours after IV injection of the test substances. Lifting of the foot indicated the test end point.


RESULTS
The three alpha2-agonists caused a temporary increase in nociceptive thresholds with a maximal effect within 15 minutes and a return to baseline levels within 1 hour. Using electrical current testing nociceptive thresholds were significantly different from placebo (mean +/- SD) for detomidine at 15 minutes (from control 5.8 +/- 0.9 to 23.3 +/- 3.9 mA, p = 0.0066) and 30 minutes (from control 6.6 +/- 1.1 to 18.8 +/- 3.3 mA, p = 0.0091). The difference was significant for romifidine at 15 minutes only (from control 5.8 +/- 0.9 to 18.7 +/- 3.8 mA, p = 0.0066). With mechanical pressure testing nociceptive thresholds were significantly different from control for detomidine at 15 minutes (from 3.2 +/- 0.2 to 6.2 +/- 0.5 N, p = 0.00076) and 30 minutes (from 3.2 +/- 0.7 to 5.7 +/- 0.8 N, p = 0.0167). The difference was significant for xylazine at 15 minutes (from control 3.2 +/- 0.2 to 5.6 +/- 0.7 N, p = 0.0079). At 15 minutes the order of magnitude of the measured antinociceptive effect was significantly different between the two pain tests for both romifidine and detomidine, but not for xylazine. For romifidine, the increase of mean thresholds compared to placebo was 4.0 +/- 1.3 times placebo levels with the electrical current test compared to 1.3 +/- 0.3 times for the mechanical pressure test (p = 0.037). For detomidine, the increase of mean thresholds compared to placebo was 5.4 +/- 1.7 times control levels with the electrical current test compared to 2.0 +/- 0.2 times for the mechanical pressure test (p = 0.040). This represents a 2.7 (romifidine) and 3.4 times (detomidine) greater increase in thresholds using electrical current testing compared to the use of mechanical pressure testing.


CONCLUSIONS
This study demonstrates the analgesic potential of alpha2-agonists in the horse for somatic pain and that they can have quantitatively different antinociceptive effects according to the antinociceptive test used.
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D000818:Animals; D018592:Cross-Over Studies; D005260:Female; D006736:Horses / Q000502:physiology*; D007093:Imidazoles; D008297:Male; D016037:Single-Blind Method; D014991:Xylazine
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D007093:Imidazoles; D014991:Xylazine; C041255:detomidine; C076257:romifidine