Institute of Physiology 1, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
Sci Rep. 2019 Jul 29;9(1):10928. doi: 10.1038/s41598-019-47342-x.
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.
瞬时受体电位香草酸 4 型离子通道（TRPV4）是肌肉骨骼系统中对渗透和机械刺激的重要传感器，它也参与伤害感受过程。在本研究中，我们研究了 TRPV4 离子通道在关节疼痛中的可能作用。在麻醉大鼠中，我们记录了供应膝关节内侧的机械敏感伤害性 A∂-和 C-纤维的反应。向膝关节内注射 TRPV4 拮抗剂 RN-1734 可降低正常关节 C-纤维对有害机械刺激的反应，以及急性炎症关节中敏化 C-纤维对无害和有害机械刺激的反应。RN-1734 对伤害性 A∂-纤维的反应没有明显改变。TRPV4 激动剂 4αPDD、GSK 1016790A 和 RN-1747 关节内应用并不一致改变 A∂-和 C-纤维对关节机械刺激的反应，也不引起持续活动。我们得出结论，TRPV4 离子通道参与正常关节有害机械刺激引起的 C 纤维反应，以及关节炎症期间 C 纤维对关节机械刺激敏感性增强。
