TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain.
TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain.
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DOI：
10.1007/s12035-018-1076-y
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发表时间：
2019-01
影响因子：
5.1
通讯作者：
Tao F
中科院分区：
文献类型：
--
作者：
Bai Q;Liu S;Shu H;Tang Y;George S;Dong T;Schmidt BL;Tao F
先前的研究表明，在完全弗氏佐剂（CFA）治疗的颞下颌关节（TMJ）组织中，肿瘤坏死因子α（TNFα）显着增加。然而，尚不清楚三叉神经伤害感受系统中的 TNFα 是否有助于颞下颌关节疼痛的发生。在本研究中，我们研究了 TNFα 在三叉神经节 (TG) 和三叉神经尾核 (Sp5C) 中在 CFA 诱导的炎症性 TMJ 疼痛中的作用。颞下颌关节内注射 CFA（10 μl，5 mg/ml）会引起 WT 小鼠三叉神经 V2 和 V3 神经支配的皮肤区域的炎性疼痛，这种疼痛在 CFA 后第 1 天出现，并持续至少 10 天。注射 CFA 后，WT 小鼠 TG 和 Sp5C 中的 TNFα 均上调。在 TNFα KO 小鼠中，CFA 诱导的 TMJ 疼痛得到显着抑制。免疫荧光染色显示，TMJ 内注射 CFA 不仅增强了 TG 和 Sp5C 中 TNFα 与 Iba1（小胶质细胞标记物）的共定位，而且还显着增加了 Sp5C 神经元中 TNFα 的表达。通过甲基化DNA免疫沉淀测定，我们还发现注射CFA后，TG中TNF基因启动子区域的DNA甲基化显着减少，表明表观遗传调控可能参与了我们模型中CFA增强的TNFα表达。我们的结果表明，三叉神经伤害感受系统中的 TNFα 在 CFA 诱导的炎症性 TMJ 疼痛中发挥着关键作用。
Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund’s adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.
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影响因子：
3
作者：
Spears, R;Oakes, R;Hutchins, B
通讯作者：
Hutchins, B
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
DOI：
10.1016/s0266-4356(02)00215-2
发表时间：
2002-10-01
影响因子：
1.8
作者：
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通讯作者：
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影响因子：
7.6
作者：
Spears, R;Oakes, R;Hutchins, B
通讯作者：
Hutchins, B
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影响因子：
5.1
作者：
Liu S;Zhao Z;Guo Y;Shu H;Li C;Tang Y;Xing Y;Tao F
通讯作者：
Tao F