Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity.
Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity.
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DOI：
10.1186/s13041-022-00970-3
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发表时间：
2022-10-26
期刊：
影响因子：
3.6
通讯作者：
Wu, Long-Jun
中科院分区：
文献类型：
--
作者：
Gu, Nan;Yi, Min-Hee;Murugan, Madhuvika;Xie, Manling;Parusel, Sebastian;Peng, Jiyun;Eyo, Ukpong B.;Hunt, Christine L.;Dong, Hailong;Wu, Long-Jun
小胶质细胞是中枢神经系统（CNS）的高度动态免疫细胞。小胶质过程与神经元元件的相互作用以分钟为单位不断发生。这种急性小胶质细胞-神经元相互作用的功能意义及其在疼痛背景下的潜在作用在很大程度上仍然未知。在这里，我们发现脊髓小胶质细胞的过程运动性和电生理反应性在福尔马林诱导的急性、持续性炎症性疼痛小鼠模型的损伤后一小时内增加。使用消融策略特异性地消耗中枢神经系统中的常驻小胶质细胞，我们证明了小胶质细胞通过放大脊髓背角的神经元活动参与福尔马林诱导的急性持续性疼痛行为。此外，我们发现P2Y12受体在中枢神经系统的小胶质细胞中特异性表达，是福尔马林诱导疼痛的小胶质细胞功能所必需的。综上所述，我们的研究为小胶质细胞和P2Y12受体在炎症性疼痛中的作用提供了新的见解，可以用于潜在的治疗策略。在线版本包含补充材料，可在10.1186/s13041-022-00970-3获得。
Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in inflammatory pain that could be used for potential therapeutic strategies. The online version contains supplementary material available at 10.1186/s13041-022-00970-3.
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