Antihyperalgesic effect of CB1 receptor activation involves the modulation of P2X3 receptor in the primary afferent neuron
Autor: | Dionéia Araldi, Cristiane I. Zanoni, Luis Paulo Manzo, Maria Cláudia G. Oliveira-Fusaro, Elayne Vieira Dias, Cláudia Herrera Tambeli, Ivan José Magayewski Bonet, Gilson Gonçalves dos Santos, Carlos Amílcar Parada |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Agonist AM251 medicine.medical_specialty Cannabinoid receptor medicine.drug_class medicine.medical_treatment Pharmacology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Cannabinoid receptor type 2 Receptor Chemistry Endocannabinoid system 030104 developmental biology Endocrinology nervous system Hyperalgesia lipids (amino acids peptides and proteins) Cannabinoid medicine.symptom 030217 neurology & neurosurgery medicine.drug |
Zdroj: | European Journal of Pharmacology. 798:113-121 |
ISSN: | 0014-2999 |
DOI: | 10.1016/j.ejphar.2017.01.030 |
Popis: | Cannabinoid system is a potential target for pain control. Cannabinoid receptor 1 (CB1) activation play a role in the analgesic effect of cannabinoids once it is expressed in primary afferent neurons. This study investigates whether the anti-hyperalgesic effect of CB1 receptor activation involves P2X3 receptor in primary afferent neurons. Mechanical hyperalgesia was evaluated by electronic von Frey test. Cannabinoid effect was evaluated using anandamide or ACEA, a non-selective or a selective CB1 receptor agonists, respectively; AM251, a CB1 receptor antagonist, and antisense ODN for CB1 receptor. Calcium imaging assay was performed to evaluated α,β-meATP-responsive cultured DRG neurons pretreated with ACEA. Anandamide or ACEA administered in peripheral tissue reduced the carrageenan-induced mechanical hyperalgesia. The reduction in the carrageenan-induced hyperalgesia induced by ACEA was completely reversed by administration of AM251 as well as by the intrathecal treatment with antisense ODN for CB1 receptor. Also, ACEA reduced the mechanical hyperalgesia induced by bradykinin and by α,β-meATP, a P2X3 receptor non-selective agonist, but not by tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and chemokine-induced chemoattractant-1 (CINC-1). Finally, CB1 receptors are co-localized with P2X3 receptors in DRG small-diameter neurons and the treatment with ACEA reduced the number of α,β-meATP-responsive cultured DRG neurons. Our data suggest that the analgesic effect of CB1 receptor activation is mediated by a negative modulation of the P2X3 receptor in the primary afferent neurons. |
Databáze: | OpenAIRE |
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