Antihyperalgesic effect of CB1 receptor activation involves the modulation of P2X(3) receptor in the primary afferent neuron

作者：Goncalves Oliveira Fusaro Maria Claudia; Silva Zanoni Cristiane Isabel; dos Santos Gilson Goncalves; Manzo Luis Paulo; Araldi Dioneia; Magayewski Bonet Ivan Jose; Tambeli Claudia Herrera; Dias Elayne Vieira^*; Parada Carlos Amilcar

来源：European Journal of Pharmacology, 2017, 798: 113-121.

DOI：10.1016/j.ejphar.2017.01.030

• CB1 receptor
• P2X(3) receptor
• Carrageenan
• Hyperalgesia
• Rat

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 P2X(3) 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 CBI receptor agonists, respectively; AM251, a CB1 receptor antagonist, and antisense ODN for CB1. receptor. Calcium imaging assay was performed to evaluated alpha,beta-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 carrageenaninduced 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 alpha,beta-meATP, a P2X(3) receptor non-selective agonist, but not by tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and chemokine-induced chemoattractant-1 (CINC-1). Finally, CBI receptors are co-localized with P2X(3) receptors in DRG small-diameter neurons and the treatment with ACEA reduced the number of alpha,beta-meATP-responsive cultured DRG neurons. Our data suggest that the analgesic effect of CB1. receptor activation is mediated by a negative modulation of the P2X(3) receptor in the primary afferent neurons.

• 出版日期2017-3-5