Transient Receptor Potential vanilloid 4 ion channel in C-fibres is involved in mechanonociception of the normal and inflamed joint

The Transient Receptor Potential vanilloid 4 ion channel (TRPV4) is an important sensor for osmotic and mechanical stimuli in the musculoskeletal system, and it is also involved in processes of nociception. In this study we investigated the putative role of TRPV4 ion channels in joint pain. In anesthetized rats we recorded from mechanosensitive nociceptive A∂- and C-fibres supplying the medial aspect of the knee joint. The intraarticular injection of the TRPV4 antagonist RN-1734 into the knee joint reduced the responses of C-fibres of the normal joint to noxious mechanical stimulation and the responses of the sensitized C-fibres of the acutely inflamed joint to innocuous and noxious mechanical stimulation. The responses of nociceptive A∂-fibres were not significantly altered by RN-1734. The intraarticular application of the TRPV4 agonists 4αPDD, GSK 1016790 A, and RN-1747 did not consistently alter the responses of A∂- and C-fibres to mechanical stimulation of the joint nor did they induce ongoing activity. We conclude that TRPV4 ion channels are involved in the responses of C-fibres to noxious mechanical stimulation of the normal joint, and in the enhanced sensitivity of C-fibres to mechanical stimulation of the joint during inflammation of the joint.