Mol Pain
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Transient receptor potential vanilloid 1 (TRPV1) channels are important membrane sensors on peripheral nerve endings and on supportive non-neuronal synoviocytes in the knee joint. TRPV 1 ion channels respond with activation of calcium and sodium fluxes to pH, thermal, chemical, osmotic, mechanical and other stimuli abundant in inflamed joints. In the present study, the kaolin/carrageenan (k/c) induced knee joint arthritis model in rats, as well as primary and clonal human synoviocyte cultures were used to understand the reciprocal interactions between reactive nitroxidative species (ROS) and functional TRPV1 channels. ROS generation was monitored with ROS sensitive dyes using live cell imaging in vitro and in spinal tissue histology, as well as with measurement of ROS metabolites in culture media using HPLC. ⋯ The results demonstrate that contributions of ROS to pronociceptive responses and neurogenic inflammation are mediated both centrally and peripherally. Responses are mediated by TRPV1 locally in the knee joint by synoviocytes, as well as by ROS-induced sensitization in the spinal cord. These findings and those of others reported in the literature indicate reciprocal interactions between TRPV1 and ROS play critical roles in the pathological and nociceptive responses active during arthritic inflammation.