Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, CEP 13083-862, Brazil.
Department of Physiological Sciences, Center of Biological Sciences, Graduate Program in Neurosciences, Federal University of Santa Catarina (UFSC), Florianopolis, SC, Brazil.
Mol Neurobiol. 2017 Oct;54(8):6174-6186. doi: 10.1007/s12035-016-0146-2. Epub 2016 Oct 5.
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.
骨关节炎（OA）是一种退行性和进行性疾病，其特征为软骨破坏和滑膜膜炎症，导致残疾、关节肿胀和疼痛。嘌呤能 P2X3 和 P2X2/3 受体有助于炎症性痛觉过敏的发展，参与膝关节关节炎过程，并在软骨细胞和支配膝关节的伤害性传入纤维中表达。在这项研究中，我们假设内源性 ATP（三磷酸腺苷）激活 P2X3 和 P2X2/3 受体通过依赖于先前释放促炎细胞因子和/或中性粒细胞迁移的初级传入伤害感受器的间接敏化，引起雄性和雌性大鼠膝关节关节痛觉过敏。我们发现，关节 P2X3 和 P2X2/3 受体的阻断以相似的方式显著减弱了雄性和动情期雌性大鼠角叉菜胶诱导的膝关节痛觉过敏。角叉菜胶诱导的膝关节炎症增加了软骨关节软骨中 P2X3 受体的表达。此外，关节 P2X3 和 P2X2/3 受体的阻断显著降低了角叉菜胶诱导的 TNF-α、IL-6 和 CINC-1 浓度升高和中性粒细胞迁移。这些发现表明，内源性 ATP 激活 P2X3 和 P2X2/3 受体对于膝关节痛觉过敏的发展是必要的，这种发展通过依赖于先前释放促炎细胞因子和/或中性粒细胞迁移的初级传入伤害感受器的间接敏化。
