title: Antihyperalgesic effect of CB1receptor activation involves the modulation of P2X3receptor in the primary afferent neuron.
abstract: 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 CB1receptor activation involves P2X3receptor 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 CB1receptor agonists, respectively; AM251, a CB1receptor antagonist, and antisense ODN for CB1receptor. 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 CB1receptor. Also, ACEA reduced the mechanical hyperalgesia induced by bradykinin and by α,β-meATP, a P2X3receptor 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, CB1receptors are co-localized with P2X3receptors 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 CB1receptor activation is mediated by a negative modulation of the P2X3receptor in the primary afferent neurons.
authors.affiliation: School of Applied Sciences, State University of Campinas, Limeira, 13484-350 São Paulo, Brazil.
authors.forename: Maria Cláudia Gonçalves
authors.initials: MCG
authors.lastname: Oliveira-Fusaro
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ribeirão Preto University of São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brazil.
authors.forename: Cristiane Isabel Silva
authors.initials: CIS
authors.lastname: Zanoni
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil.
authors.forename: Gilson Gonçalves
authors.initials: GG
authors.lastname: Dos Santos
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil.
authors.forename: Luis Paulo
authors.initials: LP
authors.lastname: Manzo
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil.
authors.forename: Dionéia
authors.initials: D
authors.lastname: Araldi
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil.
authors.forename: Ivan José Magayewski
authors.initials: IJM
authors.lastname: Bonet
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil.
authors.forename: Cláudia Herrera
authors.initials: CH
authors.lastname: Tambeli
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil. Electronic address: elayne.vieira@gmail.com.
authors.forename: Elayne Vieira
authors.initials: EV
authors.lastname: Dias
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862 São Paulo, Brazil.
authors.forename: Carlos Amilcar
authors.initials: CA
authors.lastname: Parada
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002351:Carrageenan / Q000494:pharmacology; D048429:Cell Size; D016207:Cytokines / Q000378:metabolism; D005727:Ganglia, Spinal / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020319:Oligodeoxyribonucleotides, Antisense; D043884:Receptor, Cannabinoid, CB1; D058477:Receptors, Purinergic P2X3; D002351:Carrageenan; D001920:Bradykinin
keywords: CB(1) receptor; Carrageenan; Hyperalgesia; P2X(3) receptor; Rat