Department of Anatomy, Cellular and Molecular Research Group, Faculty of Medicine, Masaryk University, Kamenice 3, 62500, Brno, Czech Republic.
Histochem Cell Biol. 2020 Apr;153(4):239-255. doi: 10.1007/s00418-020-01850-4. Epub 2020 Feb 4.
Glial cells activated by peripheral nerve injury contribute to the induction and maintenance of neuropathic pain by releasing neuromodulating cytokines and chemokines. We investigated the activation of microglia and astrocytes as well as the cellular distribution of the chemokine CCL2 and its receptor CCR2 in the trigeminal subnucleus caudalis (TSC) ipsilateral and contralateral to infraorbital nerve ligature (IONL). The left infraorbital nerve was ligated under aseptic conditions, and sham controls were operated without nerve ligature. Tactile hypersensitivity was significantly increased bilaterally in vibrissal pads of both sham- and IONL-operated animals from day 1 to 7 and tended to normalize in sham controls surviving for 14 days. Activated microglial cells significantly increased bilaterally in the TSC of both sham- and IONL-operated animals with a marked but gradual increase in the ipsilateral TSC from 1 to 7 days followed by a decrease by day 14. In contrast, robust activation of astrocytes was found bilaterally in the TSC of IONL-operated rats from 3 to 14 days with a transient activation in the ipsilateral TSC of sham-operated animals. Cellular distribution of CCL2 varied with survival time. CCL2 immunofluorescence was detected in neurons within 3 days and in astrocytes at later time points. In contrast, CCR2 was found only in astrocytes at all time points with CCR2 intensity being dominant in the ipsilateral TSC. In summary, our results reveal bilateral activation of microglial cells and astrocytes as well as changes in the cellular distribution of CCL2 and its receptor CCR2 in the TSC during the development and maintenance of orofacial neuropathic pain.
外周神经损伤激活的神经胶质细胞通过释放神经调节细胞因子和趋化因子，有助于诱导和维持神经性疼痛。我们研究了三叉神经尾核（TSC）同侧和对侧眶下神经结扎（IONL）后小胶质细胞和星形胶质细胞的激活以及趋化因子 CCL2 及其受体 CCR2 的细胞分布。在无菌条件下结扎左侧眶下神经，假手术对照组不结扎神经。触觉超敏反应在结扎和假手术对照组动物的触须垫双侧均显著增加，从第 1 天到第 7 天，在存活 14 天的假手术对照组中趋于正常。在结扎和假手术对照组动物的 TSC 中，激活的小胶质细胞双侧均显著增加，同侧 TSC 从第 1 天到第 7 天呈明显但逐渐增加趋势，然后在第 14 天减少。相比之下，在 IONL 操作的大鼠 TSC 中，星形胶质细胞的激活在双侧均较强，从第 3 天到第 14 天，假手术对照组动物同侧 TSC 中有短暂的激活。CCL2 的细胞分布随存活时间而变化。CCL2 免疫荧光在第 3 天内在神经元中检测到，在稍后的时间点在星形胶质细胞中检测到。相反，在所有时间点仅在星形胶质细胞中发现 CCR2，同侧 TSC 中 CCR2 强度占主导地位。总之，我们的结果表明，在口面神经性疼痛的发展和维持过程中，TSC 中存在双侧小胶质细胞和星形胶质细胞的激活以及 CCL2 和其受体 CCR2 的细胞分布变化。
