Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Objective. To investigate the endogenous involvement of transient receptor potential vanilloid I (TRPV1) in a model of knee joint inflammation in the mouse. Methods. Following characterization of wild-type (WT) and TRPV1-knockout mice, inflammation was induced via intraarticular (IA) injection of Freund's complete adjuvant (CIA). Knee swelling was assessed as diameter, and inflammatory heat hyperalgesia was determined using the Hargreaves technique, for up to 3 weeks. At 18 hours, acute hyperpermeability was measured with I-125-albumin, and cytokines and myeloperoxidase activity, a marker of neutrophils, were assayed in synovial fluid extracts. The possibility that exogenous tumor necrosis factor alpha (TNF alpha) was involved in influencing TRPV1 activation was investigated in separate experiments. Results. Increased levels of knee swelling, hyperpermeability, leukocyte accumulation, and TNFa were found in WT mice 18 hours after IA CFA treatment compared with saline treatment. Significantly less knee swelling and hyperpermeability were found in TRPV1(-/-) mice, but leukocyte accumulation and TNFa levels were similar in WT and TRPV1(-/-) mice. Knee swelling in response to CFA remained significantly higher for a longer period in WT mice compared with TRPV1(-/-) mice, with thermal hyperalgesic sensitivity observed at 24 hours and at I week in WT, but not TRPV1(-/-), mice. Knee swelling was attenuated (P < 0.05) in TRPV1(-/-) compared with WT mice 4 hours after IA administration of TNF alpha. Conclusion. Our findings indicate that TRPV1 has a role in acute and chronic inflammation in the mouse knee joint. Thus, selective antagonism of TRPV1 should be considered as a potential target for treatment of acute and chronic joint inflammation.