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α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system.
Pharmacol Rep. 2020 Feb; 72(1):96-103.PR

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 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.

CONCLUSIONS

The 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.

Authors+Show Affiliations

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.Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31.270-100, Brazil.Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34, Comprensorio Olivetti, 80078, Pozzuoli, NA, Italy.Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34, Comprensorio Olivetti, 80078, Pozzuoli, NA, Italy.Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34, Comprensorio Olivetti, 80078, Pozzuoli, NA, Italy.Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31.270-100, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32016857

Citation

Romero, Thiago Roberto Lima, et al. "Α2-Adrenoceptor Agonist Induces Peripheral Antinociception Via the Endocannabinoid System." Pharmacological Reports : PR, vol. 72, no. 1, 2020, pp. 96-103.
Romero TRL, Miranda E Castor MG, Parrella C, et al. Α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system. Pharmacol Rep. 2020;72(1):96-103.
Romero, T. R. L., Miranda E Castor, M. G., Parrella, C., Piscitelli, F., Di Marzo, V., & Duarte, I. D. G. (2020). Α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system. Pharmacological Reports : PR, 72(1), 96-103. https://doi.org/10.1007/s43440-019-00053-6
Romero TRL, et al. Α2-Adrenoceptor Agonist Induces Peripheral Antinociception Via the Endocannabinoid System. Pharmacol Rep. 2020;72(1):96-103. PubMed PMID: 32016857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system. AU - Romero,Thiago Roberto Lima, AU - Miranda E Castor,Marina Gomes, AU - Parrella,Cosimo, AU - Piscitelli,Fabiana, AU - Di Marzo,Vincenzo, AU - Duarte,Igor Dimitri Gama, Y1 - 2020/01/10/ PY - 2019/05/17/received PY - 2019/12/11/accepted PY - 2019/11/05/revised PY - 2020/2/5/entrez PY - 2020/2/6/pubmed PY - 2020/10/30/medline KW - Anandamide KW - CB1 cannabinoid KW - Peripheral antinociception KW - Xylazine KW - α2-Adrenoceptor SP - 96 EP - 103 JF - Pharmacological reports : PR JO - Pharmacol Rep VL - 72 IS - 1 N2 - 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 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. CONCLUSIONS: The 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. SN - 1734-1140 UR - https://www.unboundmedicine.com/medline/citation/32016857/α2_Adrenoceptor_agonist_induces_peripheral_antinociception_via_the_endocannabinoid_system_ DB - PRIME DP - Unbound Medicine ER -