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.