C-X-C motif chemokine ligand 1 and its receptor C-X-C motif chemokine receptor 2 in trigeminal ganglion contribute to nerve injury-induced orofacial mechanical allodynia
C-X-C motif chemokine ligand 1 and its receptor C-X-C motif chemokine receptor 2 in trigeminal ganglion contribute to nerve injury-induced orofacial mechanical allodynia
复制标题
三叉神经节中的C-X-C基序趋化因子配体1及其受体C-X-C基序趋化因子受体2导致神经损伤引起的口面部机械异常性疼痛
DOI：
10.1111/joor.13273
复制
发表时间：
2022
影响因子：
2.9
通讯作者：
Shen Jie-Fei
中科院分区：
文献类型：
--
作者：
Yang Jie;Liu Fei;Zhang Yan-Yan;Lin Jiu;Li Yue-Ling;Zhou Cheng;Li Chun-Jie;Shen Jie-Fei
研究背景三叉神经损伤引起的口面部异位痛是牙科治疗的严重并发症。 C-X-C基序趋化因子配体1（CXCL1）及其主要受体C-X-C基序趋化因子受体2（CXCR2）有助于脊髓神经系统神经病理性疼痛的发生和维持，但它们在三叉神经病理性感觉中的作用仍知之甚少。 目的本研究旨在探讨CXCL1和CXCR2在调节口面部异位机械性异常性疼痛中的确切作用及其潜在的下游机制。三叉神经节 (TG)。方法在下牙槽神经 (IAN) 横断 (IANX) 后评估 C57BL/6 小鼠的缩头阈值 (HWT)。然后，使用免疫组织化学、实时逆转录定量聚合酶链反应和蛋白质印迹进一步测量 CXCL1 和 CXCR2 在 TG 中的分布和表达及其潜在下游机制。此外，还检查了 SB225002（CXCR2 抑制剂）对机械异常性疼痛的影响。使用学生测试和方差分析 (ANOVA) 对数据进行分析。结果IANX 引发持续（>21 天）机械异常性疼痛以及 TG 中 CXCL1 和 CXCR2 的上调。此外，外源性 CXCL1 还降低了 HWT，CXCR2 和蛋白激酶 C (PKC) 拮抗剂可减轻 HWT (p < .05)。此外，IANX 增加了磷酸化 PKC (p-PKC) 水平并降低了电压门控钾通道 (Kv) 的表达，并且这些效应可通过抑制 CXCR2 来逆转 (p< 0.05)。结论我们的结果表明，CXCR2 通过 PKC 信号通路下调 Kv1.4 和 Kv1.1 参与口面部异位机械性异常性疼痛。这种机制可能是制定异位口面部疼痛治疗策略的潜在目标。
BackgroundOrofacial ectopic pain induced by trigeminal nerve injury is a serious complication of dental treatment. C‐X‐C motif chemokine ligand 1 (CXCL1) and its primary receptor C‐X‐C motif chemokine receptor 2 (CXCR2) contribute to the development and maintenance of neuropathic pain in the spinal nervous system, but their roles in trigeminal neuropathic sensation are still poorly understood.ObjectivesThis study aimed to investigate the exact role of CXCL1 and CXCR2 in the regulation of orofacial ectopic mechanical allodynia and their potential downstream mechanisms in the trigeminal ganglion (TG).MethodsThe head withdrawal threshold (HWT) of C57BL/6 mice was evaluated after inferior alveolar nerve (IAN) transection (IANX). Then, the distribution and expression of CXCL1 and CXCR2, and their potential downstream mechanisms in the TG were further measured using immunohistochemistry, real‐time reverse transcription‐quantitative polymerase chain reaction and Western blotting. Moreover, the effect of SB225002 (an inhibitor of CXCR2) on mechanical allodynia was examined. The data were analysed using the Student'sttest and a analysis of variance (ANOVA).ResultsIANX triggered persistent (>21 days) mechanical allodynia and upregulation of CXCL1 and CXCR2 in the TG. In addition, exogenous CXCL1 also lowered the HWT, which was alleviated by CXCR2 and protein kinase C (PKC) antagonists (p< .05). In addition, IANX increased the phosphorylated PKC (p‐PKC) levels and decreased the expression of voltage‐gated potassium channels (Kv), and these effects were reversed by inhibition of CXCR2 (p< .05).ConclusionOur results demonstrated that CXCR2 participated in orofacial ectopic mechanical allodynia via downregulation of Kv1.4 and Kv1.1 through the PKC signalling pathway. This mechanism may be a potential target in developing a treatment strategy for ectopic orofacial pain.