P2X3 and P2X2/3 receptors mediate mechanical hyperalgesia induced by bradykinin, but not by pro-inflammatory cytokines, PGE₂ or dopamine

Maria Cláudia Gonçalves de Oliveira Fusaro; Adriana Pelegrini-da-Silva; Dionéia Araldi; Carlos Amílcar Parada; Cláudia Herrera Tambeli

doi:10.1016/j.ejphar.2010.09.037

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P2X3 and P2X2/3 receptors mediate mechanical hyperalgesia induced by bradykinin, but not by pro-inflammatory cytokines, PGE₂ or dopamine

Journal article

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P2X3 and P2X2/3 receptors mediate mechanical hyperalgesia induced by bradykinin, but not by pro-inflammatory cytokines, PGE₂ or dopamine

Maria Cláudia Gonçalves de Oliveira Fusaro, Adriana Pelegrini-da-Silva, Dionéia Araldi, Carlos Amílcar Parada and Cláudia Herrera Tambeli

European journal of pharmacology, Vol.649(1-3), pp.177-182

12/15/2010

DOI: 10.1016/j.ejphar.2010.09.037

PMID: 20868656

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Abstract

Activation of peripheral P2X3 and P2X2/3 receptors by endogenous ATP is essential to the development of inflammatory hyperalgesia. We have previously demonstrated that this essential role of P2X3 and P2X2/3 receptors in the development of mechanical hyperalgesia induced by the inflammatory agent carrageenan is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of tumor necrosis factor alpha (TNF-α) and by a direct sensitization of the primary afferent nociceptors. Therefore, in this study we asked whether activation of P2X3 and P2X2/3 receptors contribute to the mechanical hyperalgesia induced by the inflammatory mediators involved in carrageenan-induced mechanical hyperalgesia, such as bradykinin, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), chemokine-induced chemoattractant-1 (CINC-1), prostaglandin E₂ (PGE₂) and dopamine. Co-administration of the non-selective P2X3 receptor antagonist TNP-ATP or the selective P2X3 and P2X2/3 receptor antagonist A-317491 with bradykinin, but not with TNF-α, IL-1β, IL-6, CINC-1, PGE₂ or dopamine, prevented in a dose-dependent manner the mechanical hyperalgesia. We also verified whether the activation of P2X3 and P2X2/3 receptors by endogenous ATP contributes to bradykinin-induced mechanical hyperalgesia via neutrophil migration and/or cytokine release. Co-administration of TNP-ATP or A-317491 did not affect either neutrophil migration or the increased concentration of TNF-α, IL-1β, IL-6 and CINC-1 induced by bradykinin. These findings demonstrate that the activation of P2X3 and P2X2/3 receptors by endogenous ATP mediates bradykinin-induced mechanical hyperalgesia by a mechanism that does not depend on neutrophil migration or cytokines release.

Adenosine Triphosphate - analogs & derivatives

Adenosine Triphosphate - metabolism

Animals

Bradykinin - metabolism

Cell Movement - drug effects

Cytokines - metabolism

Dinoprostone - metabolism

Dopamine - metabolism

Hyperalgesia - chemically induced

Hyperalgesia - metabolism

Hyperalgesia - prevention & control

Inflammation - chemically induced

Inflammation - metabolism

Inflammation - prevention & control

Inflammation Mediators - metabolism

Male

Nerve Tissue Proteins - antagonists & inhibitors

Nerve Tissue Proteins - metabolism

Neurons - drug effects

Neurons - metabolism

Neutrophils - drug effects

Pain Measurement

Purinergic P2X Receptor Antagonists - pharmacology

Rats

Rats, Wistar

Receptors, Purinergic P2X2 - metabolism

Receptors, Purinergic P2X3 - metabolism

Subcutaneous Tissue - drug effects

Subcutaneous Tissue - metabolism

Synaptic Transmission - drug effects

Details

Title: Subtitle: P2X3 and P2X2/3 receptors mediate mechanical hyperalgesia induced by bradykinin, but not by pro-inflammatory cytokines, PGE₂ or dopamine
Creators: Maria Cláudia Gonçalves de Oliveira Fusaro - Universidade Estadual de Campinas (UNICAMP)
Adriana Pelegrini-da-Silva - Universidade Estadual de Campinas (UNICAMP)
Dionéia Araldi - Universidade Estadual de Campinas (UNICAMP)
Carlos Amílcar Parada - Universidade Estadual de Campinas (UNICAMP)
Cláudia Herrera Tambeli - Universidade Estadual de Campinas (UNICAMP)
Resource Type: Journal article
Publication Details: European journal of pharmacology, Vol.649(1-3), pp.177-182
DOI: 10.1016/j.ejphar.2010.09.037
PMID: 20868656
NLM abbreviation: Eur J Pharmacol
ISSN: 0014-2999
eISSN: 1879-0712
Language: English
Date published: 12/15/2010
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985178666502771

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