INTERACTION BETWEEN THE DOPAMINERGIC AND ENDOCANNABINOID SYSTEMS PROMOTES PERIPHERAL ANTINOCICEPTION.

Autor: Gonçalves de Queiroz BF; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: barbara_formiga@yahoo.com.br., Cristina de Sousa Fonseca F; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: flaviasousafonseca@gmail.com., Barra Pinto WC; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: walacebarra@gmail.com., Viana GB; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: bauer.gv@gmail.com., Irie AL; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: audreyirie3@gmail.com., de Castro Perez A; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: andreacastro2000@hotmail.com., Lima Romero TR; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: thiromero@gmail.com., Gama Duarte ID; Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: dimitri@icb.ufmg.br.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Dec 09, pp. 177195. Date of Electronic Publication: 2024 Dec 09.
DOI: 10.1016/j.ejphar.2024.177195
Abstrakt: Background: Dopamine has been widely related to pain modulation, at central and peripheral levels. In this study we aimed to investigate the mechanisms involved in peripheral antinociception, evaluating the interaction between the dopaminergic and endocannabinoid systems in this event.
Methods: Male Swiss mice (30-40 g) were pre-sensitized by administration of the hyperalgesic PGE 2 (2 μg/paw). The nociceptive threshold was measured using the paw withdrawal test.
Results: Dopamine (80 ng/paw) promoted antinociception. This effect was reversed by the CB 1 and CB 2 cannabinoid receptor antagonists AM251 (20, 40, and 80 μg/paw) and AM630 (25, 50, and 100 μg/paw). JZL (4 μg/paw), an inhibitor of the degradation of the 2-arachidonylglycerol (2-AG), potentiated the antinociceptive action of the submaximal dose of dopamine (5 ng/paw). While anandamide degradation and reuptake inhibitors (MAFP 0.5 μg/paw and VDM11 2.5 μg/paw) did not promote changes in intermediate antinociception induced by dopamine. Anandamide at a submaximal dose (12.5 ng/paw) promoted intermediate antinociception that was not potentiated by the administration of the dopamine reuptake inhibitor GBR 12783 (16 μg/paw). In contrast, the administration of GBR potentiated the intermediate antinociception induced by a submaximal dose of 2-AG (10 μg/paw). Furthermore, the dopaminergic receptor antagonists D 2 Remoxipride (4 μg/paw) and D 3 U99194 (16 μg/paw) reversed the antinociception mediated by the maximum dose of this endocannabinoid (20 μg/paw). In contrast, the D 4 receptor antagonist L-745,870 (16 μg/paw) did not change the nociceptive threshold.
Conclusions: In this way, we demonstrate the interaction between the dopaminergic and endocannabinoid systems to promote analgesia peripherally.
Competing Interests: Declaration of Competing Interest The authors state no conflict of interest.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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