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.

三叉神经性疼痛 (TNP) 是一个重要的健康问题，但其相关机制尚未完全阐明。Toll 样受体 (TLR) 最近已被证明在背根神经节中表达并参与慢性疼痛。在这里，我们显示在由部分眶下神经结扎 (pIONL) 诱导的 TNP 模型中，三叉神经节 (TG) 神经元中的 TLR8 持续增加。此外，TG 中Tlr8的缺失或敲低减弱了 pIONL 诱导的机械异常性疼痛，降低了 ERK 和 p38-MAPK 的激活，并降低了 TG 中促炎细胞因子的表达。此外，TLR8 激动剂 VTX-2337 的 TG 内注射诱导疼痛超敏反应。VTX-2337 还增加了细胞内 Ca ²⁺浓度，诱导 ERK 和 p38 的激活，并增加 TG 中促炎细胞因子的表达。这些数据表明 TLR8 通过增加 MAPK 介导的神经炎症有助于维持 TNP。靶向 TLR8 信号可能对治疗 TNP 有效。