Department of Neurology, Duke University, Durham, NC, USA.
Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, NC, USA.
Mol Pain. 2023 Jan-Dec;19:17448069231185696. doi: 10.1177/17448069231185696.
Identification of potential therapeutic targets is needed for temporomandibular disorders (TMD) pain, the most common form of orofacial pain, because current treatments lack efficacy. Considering TMD pain is critically mediated by the trigeminal ganglion (TG) sensory neurons, functional blockade of nociceptive neurons in the TG may provide an effective approach for mitigating pain associated with TMD. We have previously shown that TRPV4, a polymodally-activated ion channel, is expressed in TG nociceptive neurons. Yet, it remains unexplored whether functional silencing of TRPV4-expressing TG neurons attenuates TMD pain. In this study, we demonstrated that co-application of a positively charged, membrane-impermeable lidocaine derivative QX-314 with the TRPV4 selective agonist GSK101 suppressed the excitability of TG neurons. Moreover, co-administration of QX-314 and GSK101 into the TG significantly attenuated pain in mouse models of temporomandibular joint (TMJ) inflammation and masseter muscle injury. Collectively, these results suggest TRPV4-expressing TG neurons represent a potential target for TMD pain.
颞下颌关节紊乱症（TMD）疼痛是最常见的颌面疼痛形式，需要确定潜在的治疗靶点，因为目前的治疗方法缺乏疗效。鉴于 TMD 疼痛主要由三叉神经节（TG）感觉神经元介导，因此功能性阻断 TG 中的伤害感受神经元可能是减轻与 TMD 相关疼痛的有效方法。我们之前已经表明，多模式激活的离子通道 TRPV4 在 TG 伤害感受神经元中表达。然而，TRPV4 表达的 TG 神经元的功能性沉默是否能减轻 TMD 疼痛仍未被探索。在这项研究中，我们证明了带正电荷的不可渗透细胞膜的局部麻醉剂衍生物 QX-314 与 TRPV4 选择性激动剂 GSK101 共同应用可抑制 TG 神经元的兴奋性。此外，QX-314 和 GSK101 共同给药到 TG 可显著减轻 TMJ 炎症和咀嚼肌损伤的小鼠模型中的疼痛。总之，这些结果表明 TRPV4 表达的 TG 神经元可能是 TMD 疼痛的潜在治疗靶点。
