Participation of the cannabinoid system and the NO/cGMP/K ATP pathway in serotonin-induced peripheral antinociception.

Autor: Aguiar DD; Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil., Petrocchi JA; Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil., da Silva GC; Department of Physiology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil., Lemos VS; Department of Physiology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil., Castor MGME; Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil. Electronic address: marinacastor@ufmg.br., Perez AC; Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil., Duarte IDG; Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil., Romero TRL; Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2024 Jan 01; Vol. 818, pp. 137536. Date of Electronic Publication: 2023 Oct 28.
DOI: 10.1016/j.neulet.2023.137536
Abstrakt: It has already been shown that serotonin can release endocannabinoids at the spinal cord level, culminating in inhibition of the dorsal horn. At the peripheral level, cannabinoid receptors modulate primary afferent neurons by inhibiting calcium conductance and increasing potassium conductance. Studies have shown that after the activation of opioid receptors and cannabinoids, there is also the activation of the NO/cGMP/K ATP pathway, inducing cellular hyperpolarization. In this study, we evaluated the participation of the cannabinoid system with subsequent activation of the NO/cGMP/K ATP pathway in the peripheral antinociceptive effect of serotonin. The paw pressure test of mice was used in animals that had their sensitivity to pain increased due to an intraplantar injection of PGE 2 (2 μg). Serotonin (250 ng/paw), administered locally in the right hind paw, induced antinociceptive effect. CB 1 and CB 2 cannabinoid receptors antagonists, AM251 (20, 40 and 80 μg) and AM630 (25, 50 and 100 μg), respectively, reversed the serotonin-induced antinociceptive effect. MAFP (0.5 μg), an inhibitor of the FAAH enzyme that degrades anandamide, and JZL184 (3.75 μg), an inhibitor of the enzyme MAGL that degrades 2-AG, as well as the VDM11 (2.5 μg) inhibitor of anandamide reuptake, potentiated the antinociceptive effect induced by a low dose (62. 5 ng) of serotonin. In the evaluation of the participation of the NO/cGMP/K ATP pathway, the antinociceptive effect of serotonin was reversed by the administration of the non-selective inhibitor of NOS isoforms L-NOarg (12.5, 25 and 50 μg) and by the selective inhibitor for the neuronal isoform LNPA (24 μg), as well as by the soluble guanylate cyclase inhibitor ODQ (25, 50 and 100 μg). Among potassium channel blockers, only Glibenclamide (20, 40 and 80 μg), an ATP-sensitive potassium channel blocker, reversed the effect of serotonin. In addition, intraplantar administration of serotonin (250 ng) was shown to induce a significant increase in nitrite levels in the homogenate of the plantar surface of the paw of mice. Taken together, these data suggest that the antinociceptive effect of serotonin occurs by activation of the cannabinoid system with subsequent activation of the NO/cGMP/K ATP pathway.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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