• Pharmacol Rep · Feb 2020

    α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system.

    • Romero Thiago Roberto Lima TRL Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31.270-, Miranda E Castor Marina Gomes MG Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31.27, Cosimo Parrella, Fabiana Piscitelli, Vincenzo Di Marzo, and Duarte Igor Dimitri Gama IDG Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31.270-10.
    • Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31.270-100, Brazil. thiromero@gmail.com.
    • Pharmacol Rep. 2020 Feb 1; 72 (1): 96-103.

    BackgroundXylazine is an α2 adrenoceptor agonist that is extensively used in veterinary medicine and animal experimentation procedures to produce analgesia, sedation and muscle relaxation without causing general anesthesia. Considering the lack of knowledge of the mechanisms involved in peripheral antinociception induced by xylazine and the potential interactions between the adrenergic and endocannabinoid systems, the present study investigated the contribution of the latter system in the mechanism of xylazine.MethodsThe rat paw pressure test, in which hyperalgesia was induced by the intraplantar injection of prostaglandin E2, was performed.ResultsXylazine administered via an intraplantar injection (25, 50 and 100 μg) induced a peripheral antinociceptive effect against prostaglandin E2 (2 μg)-induced hyperalgesia. This effect was blocked by treatment with the selective CB1 cannabinoid antagonist AM251 (20, 40 and 80 μg) but not by the selective CB2 cannabinoid antagonist AM630 (100 μg). The anandamide reuptake inhibitor VDM11 (2.5 μg) intensified the peripheral antinociceptive effect of a submaximal dose of xylazine (25 μg), and the inhibitor of endocannabinoid enzymatic hydrolysis, MAFP (0.5 μg), showed a tendency towards this same effect. In addition, liquid-chromatography mass spectrometric analysis indicated that xylazine (100 μg) treatment was associated with an increase in anandamide levels in the rat paws treated with PGE2.ConclusionsThe present results provides evidence that the peripheral antinociceptive effect of the α2 adrenoceptor agonist xylazine probably results from anandamide release and subsequent CB1 cannabinoid receptor activation.

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