Canna~Fangled Abstracts

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

By January 10, 2020February 5th, 2020No Comments
2020 Feb;72(1):96-103. doi: 10.1007/s43440-019-00053-6. Epub 2020 Jan 10.

Abstract

BACKGROUND:

Xylazine 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.

METHODS:

The rat paw pressure test, in which hyperalgesia was induced by the intraplantar injection of prostaglandin E2, was performed.

RESULTS:

Xylazine 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 cannabinoidantagonist 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.

CONCLUSIONS:

The present results provides evidence that the peripheral antinociceptive effect of the α2adrenoceptor agonist xylazine probably results from anandamide release and subsequent CB1 cannabinoid receptor activation.

KEYWORDS:

Anandamide, CB1 cannabinoid, Peripheral antinociception, Xylazine, α2-Adrenoceptor

PMID: 32016857
DOI: 10.1007/s43440-019-00053-6

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