Knee osteoarthritis: a role for bradykinin?
Osteoarthritis (OA) is a painful and degenerating progressive disease of the joints which affects millions of patients worldwide. The cause of OA is largely unknown. Among the potential therapies for the symptomatic treatment of OA, the intra-articular administration of a specific bradykinin (BK) B2 receptor antagonist has been reported to produce a long lasting analgesic effect in patients affected by knee OA. BK is a vasodilator and inflammatory nonapeptide which is generated in OA synovium. It contributes to the initiation and maintenance of inflammation, to exciting and sensitizing sensory nerve fibres, thus producing pain, and to activating synoviocytes and chondrocytes which are the main cells involved in the homeostasis of synovial fluid and cartilage, respectively. Moreover, BK synergistically potentiates the effects produced by pro-inflammatory cytokines. Biochemical and preclinical evidence supporting the therapeutic relevance of B2 receptor blockade in OA pathophysiology are reviewed in this publication.
Meini
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Pharmacology Department, Menarini Ricerche S.p.A., via Rismondo 12A, 50135, Firenze, Italy. meini@menarini-ricerche.it.
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007270:Injections, Intra-Articular; D007705:Kinins / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065094:Bradykinin B2 Receptor Antagonists; D007705:Kinins; D043782:Receptor, Bradykinin B2; C065679:icatibant; D001920:Bradykinin