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

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 alpha) 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 alpha) interleukin-1 beta (IL-1 beta) interleukin 6 (IL-6) chemokine-induced chemoattractant-1 (CINC-1) prostaglandin E-2 (PGE(2)) 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 alpha IL 1 beta IL 6 CINC 1 PGE(2) 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-alpha IL 1 beta 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 (C) 2010 Published by Elsevier B V