Xylazine Induces Peripheral Antinociception by α1 -, β-Adrenoceptors and μ-, δ-Opioid Receptors Activation

Objective: Using a non-inflammatory model of hyperalgesia, this study investigated the participation of α1 and β adrenoceptors and opioid receptor subtypes in xylazine-induced peripheral antinociception in this event. Materials & Methods: Nociceptive threshold was measured using the rat pressure test in animals that were injected with prostaglandin E2, xylazine, prazosin, propranolol, clocinnamox, naltrindole or norbinaltorphimine. Male Wistar rats were used in which hyperalgesia induced by intraplantar injection of prostaglandin E2 (2 μg). Results: Xylazine was administered locally (100 μg) into the right hind paw of animals, alone and after the α1-adrenoceptor antagonist prazosin (0.5, 1 and 2 μg/paw), the β-adrenoceptor antagonist propranolol (150, 300 and 600 μg/paw), the μ-opioid antagonist clocinnamox (10, 20, and 40 μg/paw), the δ-opioid antagonist naltrindole (15, 30 and 60 μg/paw) or the κ-opioid antagonist nor-binaltorphimine (100 μg/ paw). Nociceptive threshold was measured using the rat pressure test. Intraplantar injection of xylazine induced peripheral antinociception against hyperalgesia induced by PGE2. This effect was prevented, in a dose dependent manner, by intraplantar injection of prazosin, propranolol, clocinnamox and naltrindole. However, injection of norbinaltorphimine did not alter xylazine antinociception. Conclusion: The present data provide evidence that xylazine produces peripheral antinociception by activation of α1 and β-adrenoceptor as well as involving μ and δ but not κ opioid receptors, either directly or indirectly.