• Juliana Maia Teixeira, Carlos Amílcar Parada, and Cláudia Herrera Tambeli.
• Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, UNICAMP, Rua Monteiro Lobato, 255, Campinas, SP, CEP 13083-862, Brazil.
• Inflamm. Res. 2018 Apr 1; 67 (4): 301-314.

ObjectiveWe investigated whether: (1) P2 × 7 receptor activation by its agonist (BzATP) induces articular hyperalgesia in the rat's knee joint via inflammatory mechanisms and (2) activation of P2 × 7 receptors by endogenous ATP contributes to the articular hyperalgesia induced by bradykinin, TNF-α, IL-1β, CINC-1, PGE2, and dopamine.MethodsThe articular hyperalgesia was quantified using the rat knee joint incapacitation test. The knee joint inflammation, characterized by the concentration of pro-inflammatory cytokines and by neutrophil migration, was quantified in the synovial lavage fluid by ELISA and myeloperoxidase enzyme activity assay, respectively.ResultsBzATP induced a dose-dependent articular hyperalgesia in the rat's knee joint that was significantly reduced by the selective antagonists for P2 × 7, bradykinin B1 or B2 receptors, β1 or β2 adrenoceptors, and by pre-treatment with Indomethacin. BzATP induced a local increase of TNF-α, IL-1β, IL-6, and CINC-1 concentration and neutrophil migration into the knee joint. The co-administration of the selective P2 × 7 receptor antagonist A-740003 significantly reduced the articular hyperalgesia induced by bradykinin and dopamine, but not by TNF-α, IL-1β, CINC-1, and PGE2.ConclusionsP2 × 7 receptor activation induces articular hyperalgesia mediated by the previous inflammatory mediator release. P2 × 7 receptor-induced articular hyperalgesia is sustained by the involvement of this purinergic receptor in bradykinin and dopamine-induced hyperalgesia in the knee joint.

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