Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy
Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy
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Interleukin-17 调节神经元-胶质细胞通讯、突触传递和化疗后的神经病理性疼痛
DOI：
10.1016/j.celrep.2019.10.085
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发表时间：
2019-11-19
期刊：
影响因子：
8.8
通讯作者：
Zhang, Yu-Qiu
中科院分区：
文献类型：
--
作者：
Luo, Hao;Liu, Hui-Zhu;Zhang, Yu-Qiu
促炎细胞因子白细胞介素 17 (IL-17) 与疼痛调节有关。然而，IL-17 调节疼痛传递的突触机制尚不清楚。在此，我们报告神经胶质细胞产生的 IL-17 抑制脊髓疼痛回路中的抑制性突触传递并驱动化疗引起的神经性疼痛。我们发现IL-17不仅增强小鼠脊髓切片中表达生长抑素的层IIo神经元的兴奋性突触后电流（EPSC），而且抑制抑制性突触后突触电流（IPSC）和GABA诱导的电流。 IL-17主要在脊髓星形胶质细胞中表达，其受体IL-17R在表达生长抑素的神经元中检测到。选择性敲低表达脊髓生长抑素的中间神经元中的 IL-17R 可减少紫杉醇诱导的超敏反应。脊髓星形胶质细胞中 IL-17 的过度表达足以诱发幼稚动物的机械异常性疼痛。在背根神经节中，伤害性感觉神经元中的 IL-17R 表达足以并且是紫杉醇后诱导神经元过度兴奋所必需的。总之，我们的数据表明，IL-17/IL-17R 在化疗引起的周围神经病变中介导神经元-胶质细胞相互作用和神经元过度兴奋。
The proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresses inhibitory postsynaptic synaptic currents (IPSCs) and GABA-induced currents in lamina IIo somatostatin-expressing neurons in mouse spinal cord slices. IL-17 mainly expresses in spinal cord astrocytes, and its receptor IL-17R is detected in somatostatin-expressing neurons. Selective knockdown of IL-17R in spinal somatostatin-expressing interneurons reduces paclitaxel-induced hypersensitivity. Overexpression of IL-17 in spinal astrocytes is sufficient to induce mechanical allodynia in naive animals. In dorsal root ganglia, IL-17R expression in nociceptive sensory neurons is sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate neuron-glial interactions and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy.