P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis.
P2X3 and P2X2/3 Receptors Play a Crucial Role in Articular Hyperalgesia Development Through Inflammatory Mechanisms in the Knee Joint Experimental Synovitis.
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DOI：
10.1007/s12035-016-0146-2
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发表时间：
2017-10
影响因子：
5.1
通讯作者：
Tambeli CH
中科院分区：
文献类型：
--
作者：
Teixeira JM;Bobinski F;Parada CA;Sluka KA;Tambeli CH
骨关节炎（OA）是一种退行性和进行性疾病，其特征在于软骨破坏和滑膜炎症，导致残疾、关节肿胀和疼痛。嘌呤能P2 X3和P2 X2/3受体促进炎性痛觉过敏的发展，参与膝关节的关节炎过程，并在支配膝关节的软骨细胞和伤害性传入纤维中表达。在这项研究中，我们假设内源性ATP（5′-三磷酸腺苷）激活P2 X3和P2 X2/3受体，通过依赖于先前释放的促炎细胞因子和/或中性粒细胞迁移的初级传入伤害感受器的间接致敏，诱导雄性和雌性大鼠膝关节的关节痛敏。我们发现，关节P2 X3和P2 X2/3受体的阻滞剂显着减弱角叉菜胶诱导的痛觉过敏在膝关节的雄性和发情雌性大鼠以类似的方式。角叉菜胶诱导的膝关节炎症增加了关节软骨细胞P2 X3受体的表达。此外，关节P2 X3和P2 X2/3受体的阻断显著降低了角叉菜胶诱导的TNF-α、IL-6和CINC-1浓度的升高以及中性粒细胞迁移。这些研究结果表明，P2 X3和P2 X2/3受体激活内源性ATP是必不可少的痛觉过敏的发展在膝关节通过间接敏化初级传入伤害感受器依赖于先前释放的促炎细胞因子和/或中性粒细胞迁移。
Osteoarthritis (OA) is a degenerative and progressive disease, characterized by cartilage breakdown and by synovial membrane inflammation, which results in disability, joint swelling and pain. The purinergic P2X3 and P2X2/3 receptors contribute to development of inflammatory hyperalgesia, participate in arthritis processes in the knee joint and are expressed in chondrocytes and nociceptive afferent fibers innervating the knee joint. In this study, we hypothesized that P2X3 and P2X2/3 receptors activation by endogenous ATP (adenosine 5′-triphosphate) induces articular hyperalgesia in the knee joint of male and female rats through an indirect sensitization of primary afferent nociceptors dependent on the previous release of pro-inflammatory cytokines and/or on neutrophil migration. We found that the blockade of articular P2X3 and P2X2/3 receptors significantly attenuated carrageenan-induced hyperalgesia in the knee joint of male and estrus female rats in a similar manner. The carrageenan-induced knee joint inflammation increased the expression of P2X3 receptors in chondrocytes of articular cartilage. Further, the blockade of articular P2X3 and P2X2/3 receptors significantly reduced the increased concentration of TNF-α, IL-6 and CINC-1 and the neutrophil migration induced by carrageenan. These findings indicate that P2X3 and P2X2/3 receptors activation by endogenous ATP is essential to hyperalgesia development in the knee joint through an indirect sensitization of primary afferent nociceptors dependent on the previous release of pro-inflammatory cytokines and/or on neutrophil migration.