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Role of transient receptor potential vanilloid 4 in rat joint inflammation Denadai-Souza A; Martin L; de Paula MA; de Avellar MC; Muscara MN; Vergnolle N; Cenac NArthritis Rheum 2012[Jun]; 64 (6): 1848-58OBJECTIVE: To determine whether activation of transient receptor potential vanilloid 4 (TRPV-4) induces inflammation in the rat temporomandibular joint (TMJ), and to assess the effects of TRPV-4 agonists and proinflammatory mediators, such as a protease-activated receptor 2 (PAR-2) agonist, on TRPV-4 responses. METHODS: Four hours after intraarticular injection of carrageenan into the rat joints, expression of TRPV-4 and PAR-2 in trigeminal ganglion (TG) neurons and in the TMJs were evaluated by real-time reverse transcription-polymerase chain reaction and immunofluorescence, followed by confocal microscopy. The functionality of TRPV-4 and its sensitization by a PAR-2-activating peptide (PAR-2-AP) were analyzed by measuring the intracellular Ca(2+) concentration in TMJ fibroblast-like synovial cells or TG neurons. Plasma extravasation, myeloperoxidase activity, and the head-withdrawal threshold (index of mechanical allodynia) were evaluated after intraarticular injection of selective TRPV-4 agonists, either injected alone or coinjected with PAR-2-AP. RESULTS: In the rat TMJs, TRPV-4 and PAR-2 expression levels were up-regulated after the induction of inflammation. Two TRPV-4 agonists specifically activated calcium influx in TMJ fibroblast-like synovial cells or TG neurons. In vivo, the agonists triggered dose-dependent increases in plasma extravasation, myeloperoxidase activity, and mechanical allodynia. In synovial cells or TG neurons, pretreatment with PAR-2-AP potentiated a TRPV-4 agonist-induced increase in [Ca(2+) ](i) . In addition, TRPV-4 agonist-induced inflammation was potentiated by PAR-2-AP in vivo. CONCLUSION: In this rat model, TRPV-4 is expressed and functional in TG neurons and synovial cells, and activation of TRPV-4 in vivo causes inflammation in the TMJ. Proinflammatory mediators, such as PAR-2 agonists, sensitize the activity of TRPV-4. These results identify TRPV-4 as an important signal of inflammation in the joint.|Animals[MESH]|Calcium/metabolism[MESH]|Carrageenan[MESH]|Gene Expression[MESH]|Hyperalgesia/genetics/metabolism[MESH]|Inflammation/chemically induced/*metabolism[MESH]|Male[MESH]|Neurons/drug effects/*metabolism[MESH]|Oligopeptides/pharmacology[MESH]|Phorbol Esters/pharmacology[MESH]|Rats[MESH]|Rats, Wistar[MESH]|Receptor, PAR-2/agonists/genetics/metabolism[MESH]|Synovial Membrane/drug effects/*metabolism[MESH]|TRPV Cation Channels/agonists/genetics/*metabolism[MESH]|Temporomandibular Joint/drug effects/*metabolism[MESH] |
