Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.
Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.
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DOI：
10.1016/j.pain.2013.04.004
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发表时间：
2013-08
期刊：
影响因子：
7.4
通讯作者：
Liedtke W
中科院分区：
文献类型：
--
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
颞下颌关节紊乱病（TMJD）以其咀嚼相关疼痛而闻名。TMJD是医学相关的，因为它的患病率，严重性，慢性，和“治疗难治性”的疼痛，其主要是难以捉摸的发病机制。在此背景下，我们试图调查的钙渗透TRPV 4离子通道，强烈表达在三叉神经节感觉神经元，颞下颌关节炎症和疼痛行为的发病机制的贡献。我们在这里证明，TRPV 4是至关重要的TMJ炎症诱发的疼痛行为的小鼠，三叉神经节的伤害性变化是TRPV 4依赖性的。作为定量指标，咬合力被记录为咀嚼致敏的证据，与人类翻译研究一致。在患有TMJ炎症的Trpv 4 −/−小鼠中，咬合力的衰减明显小于WT小鼠。全身应用特异性TRPV 4抑制剂也观察到类似的效果。CFA注射后TMJ炎症和下颌骨变化明显，但显着独立于Trpv 4基因型。有趣的是，作为TMJ炎症的结果，WT小鼠在TMJ支配的三叉神经感觉神经元中表现出TRPV 4和磷酸化ERK的显著上调，而在Trpv 4 −/−小鼠中不存在。神经元中MEK/ERK磷酸化基因受损的小鼠表现出与Trpv 4 −/−小鼠相似的对咬合力降低的抵抗力。因此，TRPV 4是TMJ炎症中咀嚼敏化所必需的，并且可能在体内三叉神经节感觉神经元中的MEK/ERK磷酸化的上游起作用。因此，TRPV 4代表TMJ炎症中的新的促伤害性靶点，并且应该被认为是人类TMJD中的感兴趣的靶点。
Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, and “therapy-refractoriness” of its pain, and its largely elusive pathogenesis. Against this background we sought to investigate pathogenetic contributions of the calcium-permeable TRPV4 ion channel, robustly expressed in the trigeminal ganglion sensory neurons, to TMJ inflammation and pain behavior. We demonstrate here that TRPV4 is critical for TMJ-inflammation evoked pain behavior in mice, and that trigeminal ganglion pro-nociceptive changes are Trpv4-dependent. As a quantitative metric, bite force was recorded as evidence of masticatory sensitization, in keeping with human translational studies. In Trpv4−/− mice with TMJ-inflammation, attenuation of bite force was significantly less than in WT mice. Similar effects were seen with systemic application of a specific TRPV4 inhibitor. TMJ-inflammation and mandibular bony changes were apparent after CFA injections, but remarkably independent of Trpv4 genotype. Intriguingly, as a result of TMJ-inflammation, WT mice exhibited significant up-regulation of TRPV4 and phosphorylated ERK in TMJ-innervating trigeminal sensory neurons, absent in Trpv4−/− mice. Mice with genetically-impaired MEK/ERK phosphorylation in neurons showed a similar resistance to reduction of bite-force as Trpv4−/− mice. Thus, TRPV4 is necessary for masticatory sensitization in TMJ-inflammation, and likely functions up-stream of MEK/ERK phosphorylation in trigeminal ganglion sensory neurons in-vivo. TRPV4 therefore represents a novel pro-nociceptive target in TMJ inflammation, and should be considered a target-of-interest in human TMJD.
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影响因子：
2.9
作者：
Kogawa, E. M.;Calderon, P. S.;Conti, P. C. R.
通讯作者：
Conti, P. C. R.
影响因子：
10.4
作者：
Li J;Kanju P;Patterson M;Chew WL;Cho SH;Gilmour I;Oliver T;Yasuda R;Ghio A;Simon SA;Liedtke W
通讯作者：
Liedtke W
影响因子：
16.2
作者：
Lechner, Stefan G.;Markworth, Soeren;Lewin, Gary R.
通讯作者：
Lewin, Gary R.
DOI：
10.1073/pnas.1735416100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Liedtke, W;Friedman, JM
通讯作者：
Friedman, JM
影响因子：
2.4
作者：
ARCAN, M;ZANDMAN, F
通讯作者：
ZANDMAN, F