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

Author(s)

Teixeira, Juliana Maia ^[1] ; Parada, Carlos Amilcar ^[1] ; Tambeli, Claudia Herrera ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, UNICAMP, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

• Document type: Journal article
• Source: Inflammation Research; v. 67, n. 4, p. 301-314, APR 2018.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 10/05381-4 - Involvement of P2X3 and P2X7 purinergic receptors in carrageenan-induced arthritis in rat's knee joint
• Grantee: Claudia Herrera Tambeli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/16854-3 - Involvement of P2X3 and P2X7 purinergic receptors in carrageenan-induced arthritis in knee joint of rats
• Grantee: Juliana Maia Teixeira
• Support Opportunities: Scholarships in Brazil - Doctorate