P2X3 and P2X2/3 receptors mediate mechanical hyperalgesia induced by bradykinin, but not by pro-inflammatory cytokines, PGE2 or dopamine
P2X3 and P2X2/3 receptors mediate mechanical hyperalgesia induced by bradykinin, but not by pro-inflammatory cytokines, PGE2 or dopamine
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DOI：
10.1016/j.ejphar.2010.09.037
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发表时间：
2010-12-15
影响因子：
5
通讯作者：
Tambeli, Claudia Herrera
中科院分区：
文献类型：
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作者：
Goncalves de Oliveira Fusaro, Maria Claudia;Pelegrini-da-Silva, Adriana;Tambeli, Claudia Herrera
外周P2X3和P2X2/3受体的激活对炎症性痛觉过敏的发展是必不可少的。我们以前已经证明，在炎症性药物卡拉胶诱导的机械性痛敏中，P2X3和P2X2/3受体的这一重要作用是通过依赖于先前释放的肿瘤坏死因子α对初级传入伤害性感受器的间接敏化和初级传入伤害性感受器的直接敏化来介导的。因此，在本研究中，我们探讨了P2X3和P2X2/3受体的激活是否参与了角叉菜胶致机械性痛觉过敏所涉及的炎症介质，如肿瘤坏死因子α缓激动素所引起的机械性痛敏。IL-1β、IL-6、趋化因子诱导的趋化因子-1、前列腺素E-2(PGE(2))和多巴胺与缓激肽或选择性的P2X3和P2X2/3受体拮抗剂A 317491合用缓激肽，但不与肿瘤坏死因子αIL-1β、IL-6、CINC-1、PGE(2)或多巴胺合用，可剂量依赖性地抑制机械性痛敏。通过中性粒细胞迁移和/或细胞因子释放，联合应用TNP-ATP或A 317491并不影响中性粒细胞迁移或缓激肽诱导的肿瘤坏死因子-α、IL-1、β、IL-6和CINC-1浓度的升高。这些结果表明，内源性三磷酸腺苷激活P2X3和P2X2/3受体介导缓激肽诱导的机械性痛敏，其机制不依赖于中性粒细胞迁移或细胞因子释放(C)2010年由Elsevier B V发表
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