A cyclic pathway of P2 x 7, bradykinin, and dopamine receptor activation induces a sustained articular hyperalgesia in the knee joint of rats

作者：Teixeira Juliana Maia; Parada Carlos Amilcar; Tambeli Claudia Herrera^*

来源：Inflammation Research, 2018, 67(4): 301-314.

DOI：10.1007/s00011-017-1122-7

• P2x7 receptor
• BzATP
• Articular hyperalgesia
• Rat knee joint
• Pro-inflammatory cytokines
• Inflammatory mediators

We investigated whether: (1) P2 x 7 receptor activation by its agonist (BzATP) induces articular hyperalgesia in the rat's knee joint via inflammatory mechanisms and (2) activation of P2 x 7 receptors by endogenous ATP contributes to the articular hyperalgesia induced by bradykinin, TNF-alpha, IL-1 beta, CINC-1, PGE(2,) and dopamine.
The 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.
BzATP induced a dose-dependent articular hyperalgesia in the rat's knee joint that was significantly reduced by the selective antagonists for P2 x 7, bradykinin B-1 or B-2 receptors, beta(1) or beta(2) adrenoceptors, and by pre-treatment with Indomethacin. BzATP induced a local increase of TNF-alpha, IL-1 beta, IL-6, and CINC-1 concentration and neutrophil migration into the knee joint. The co-administration of the selective P2 x 7 receptor antagonist A-740003 significantly reduced the articular hyperalgesia induced by bradykinin and dopamine, but not by TNF-alpha, IL-1 beta, CINC-1, and PGE(2).
P2 x 7 receptor activation induces articular hyperalgesia mediated by the previous inflammatory mediator release. P2 x 7 receptor-induced articular hyperalgesia is sustained by the involvement of this purinergic receptor in bradykinin and dopamine-induced hyperalgesia in the knee joint.

• 出版日期2018-4