Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/198626
Type: Artigo de periódico
Title: Peripheral Mechanisms Underlying The Essential Role Of P2x3,2/3 Receptors In The Development Of Inflammatory Hyperalgesia.
Author: Oliveira, Maria Cláudia G
Pelegrini-da-Silva, Adriana
Tambeli, Cláudia Herrera
Parada, Carlos Amílcar
Abstract: Activation of P2X3,2/3 receptors by endogenous ATP contributes to the development of inflammatory hyperalgesia. Given the clinical importance of mechanical hyperalgesia in inflammatory states, we hypothesized that the activation of P2X3,2/3 receptors by endogenous ATP contributes to carrageenan-induced mechanical hyperalgesia and that this contribution is mediated by an indirect and/or a direct sensitization of the primary afferent nociceptors. Co-administration of the selective P2X3,2/3 receptors antagonist A-317491, or the non-selective P2X3 receptor antagonist, TNP-ATP, with carrageenan blocked the mechanical hyperalgesia induced by carrageenan, and significantly reduced the increased concentration of tumor necrosis factor alpha (TNF-alpha) and chemokine-induced chemoattractant-1 (CINC-1) but not of interleukin-1 beta (IL-1 beta) induced by carrageenan. Co-administration of the selective P2X3,2/3 receptors antagonist A-317491 with carrageenan did not affect the neutrophil migration induced by carrageenan. Intrathecal administration of oligonucleotides antisense against P2X3 receptors for seven days significantly reduced the expression of P2X3 receptors in the saphenous nerve and significantly reduced the mechanical hyperalgesia induced by carrageenan. We concluded that the activation of P2X3,2/3 receptors by endogenous ATP is essential to the development of the mechanical hyperalgesia induced by carrageenan. Furthermore, we showed that this essential role of P2X3,2/3 receptors in the development of carrageenan-induced mechanical hyperalgesia is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of TNF-alpha and by a direct sensitization of the primary afferent nociceptors.
Subject: Adenosine Triphosphate
Analysis Of Variance
Animals
Carrageenan
Cytokines
Disease Models, Animal
Dose-response Relationship, Drug
Drug Administration Routes
Enzyme-linked Immunosorbent Assay
Hyperalgesia
Inflammation
Male
Oligodeoxyribonucleotides, Antisense
Pain Measurement
Pain Threshold
Peroxidase
Phenols
Polycyclic Compounds
Polysaccharides
Purinergic P2 Receptor Antagonists
Rats
Rats, Wistar
Receptors, Purinergic P2
Receptors, Purinergic P2x2
Receptors, Purinergic P2x3
Time Factors
Citation: Pain. v. 141, n. 1-2, p. 127-34, 2009-Jan.
Rights: fechado
Identifier DOI: 10.1016/j.pain.2008.10.024
Address: http://www.ncbi.nlm.nih.gov/pubmed/19081189
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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