Silencing of TRPV4-expressing sensory neurons attenuates temporomandibular disorders pain.
Silencing of TRPV4-expressing sensory neurons attenuates temporomandibular disorders pain.
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DOI：
10.1177/17448069231185696
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发表时间：
2023-01
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
--
作者：
颞下颌紊乱（TMD）疼痛是最常见的口面部疼痛，目前的治疗方法缺乏疗效，因此需要确定潜在的治疗靶点。考虑到TMD疼痛是由三叉神经节（TG）感觉神经元介导的，对TG中的伤害性神经元进行功能阻断可能是减轻TMD相关疼痛的有效途径。我们之前已经证明TRPV4是一种多模态激活的离子通道，在TG伤害性神经元中表达。然而，表达trpv4的TG神经元的功能性沉默是否会减轻TMD疼痛仍未得到证实。在这项研究中，我们证明了带正电、膜不渗透的利多卡因衍生物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在TG中共同给药可显著减轻颞下颌关节（TMJ）炎症和咬肌损伤小鼠模型的疼痛。总的来说，这些结果表明表达trpv4的TG神经元代表了TMD疼痛的潜在靶点。
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.
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影响因子：
5.1
作者：
Luo Y;Suttle A;Zhang Q;Wang P;Chen Y
通讯作者：
Chen Y
影响因子：
7.4
作者：
Chen Y;Williams SH;McNulty AL;Hong JH;Lee SH;Rothfusz NE;Parekh PK;Moore C;Gereau RW 4th;Taylor AB;Wang F;Guilak F;Liedtke W
通讯作者：
Liedtke W
影响因子：
7.4
作者：
Kim HY;Kim K;Li HY;Chung G;Park CK;Kim JS;Jung SJ;Lee MK;Ahn DK;Hwang SJ;Kang Y;Binshtok AM;Bean BP;Woolf CJ;Oh SB
通讯作者：
Oh SB
影响因子：
2.5
作者：
Schiffman E;Ohrbach R;Truelove E;Look J;Anderson G;Goulet JP;List T;Svensson P;Gonzalez Y;Lobbezoo F;Michelotti A;Brooks SL;Ceusters W;Drangsholt M;Ettlin D;Gaul C;Goldberg LJ;Haythornthwaite JA;Hollender L;Jensen R;John MT;De Laat A;de Leeuw R;Maixner W;van der Meulen M;Murray GM;Nixdorf DR;Palla S;Petersson A;Pionchon P;Smith B;Visscher CM;Zakrzewska J;Dworkin SF;International RDC/TMD Consortium Network, International association for Dental Research;Orofacial Pain Special Interest Group, International Association for the Study of Pain
通讯作者：
Orofacial Pain Special Interest Group, International Association for the Study of Pain
影响因子：
64.8
作者：
Binshtok, Alexander M.;Bean, Bruce P.;Woolf, Clifford J.
通讯作者：
Woolf, Clifford J.