TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice.
TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice.
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三叉神经节中的 TLR8 有助于维持小鼠三叉神经病理性疼痛
DOI：
10.1007/s12264-020-00621-4
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发表时间：
2021-04
影响因子：
5.6
通讯作者：
Zhang ZJ
中科院分区：
文献类型：
--
作者：
Zhao LX;Jiang M;Bai XQ;Cao DL;Wu XB;Zhang J;Guo JS;Chen TT;Wang J;Wu H;Gao YJ;Zhang ZJ
三叉神经病理性疼痛（TNP）是一个重要的健康问题，但其机制尚未完全阐明。Toll样受体（TLR）最近已被证明在背根神经节表达，并参与慢性疼痛。在这里，我们表明，TLR 8持续增加的三叉神经节（TG）神经元的TNP模型诱导的部分眶下神经结扎（pIONL）。此外，TG中Tlr 8的缺失或敲低可减弱pIONL诱导的机械性异常性疼痛，减少ERK和p38-MAPK的活化，并降低TG中促炎细胞因子的表达。此外，TG内注射TLR 8激动剂VTX-2337诱导疼痛超敏反应。VTX-2337还增加TG中的细胞内Ca 2+浓度，诱导ERK和p38的活化，并增加促炎细胞因子的表达。这些数据表明TLR 8通过增加MAPK介导的神经炎症而有助于TNP的维持。靶向TLR 8信号传导可能对TNP的治疗有效。
Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca2+ concentration, induced the activation of ERK and p38, and increased the expression of pro-inflammatory cytokines in the TG. These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.
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影响因子：
2.9
作者：
Hawkins JL;Moore NJ;Miley D;Durham PL
通讯作者：
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