Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain
Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain
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小胶质细胞对于脊髓背角的突触可塑性和慢性疼痛是不可或缺的
DOI：
10.1016/j.celrep.2019.05.087
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发表时间：
2019-06-25
期刊：
影响因子：
8.8
通讯作者：
Wu, Long-Jun
中科院分区：
文献类型：
--
作者：
Zhou, Li-Jun;Peng, Jiyun;Wu, Long-Jun
C纤维突触的脊髓长时程增强(LTP)被认为是慢性疼痛的基础。然而，脊柱LTP和慢性疼痛之间的因果联系仍然缺乏。在这里，我们报告了高频刺激(HFS；100 Hz，10V)小鼠坐骨神经可以可靠地诱导脊髓LTP，而不会造成神经损伤。LTP诱导的刺激可触发持续超过35天的慢性疼痛，并增加脊髓背角中降钙素基因相关肽(CGRP)终末的数量。行为和形态的改变可以通过阻断NMDA受体、消融脊髓小胶质细胞或有条件地删除小胶质细胞脑源性神经营养因子(BDNF)来预防。抗集落刺激因子1(CSF-1)的抗体可抑制HFS诱导的脊髓LTP、小胶质细胞的激活和BDNF的上调。综上所述，我们的结果表明，小胶质细胞CSF1和BDNF信号在脊髓LTP和慢性疼痛中是不可或缺的。疼痛通路中依赖小胶质细胞的突触增强到结构改变的转变可能是疼痛慢性化的基础。
Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and chronic pain is still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces spinal LTP without causing nerve injury. LTP-inducible stimulation triggers chronic pain lasting for more than 35 days and increases the number of calcitonin gene-related peptide (CGRP) terminals in the spinal dorsal horn. The behavioral and morphological changes can be prevented by blocking NMDA receptors, ablating spinal microglia, or conditionally deleting microglial brain-derived neurotrophic factor (BDNF). HFS-induced spinal LTP, microglial activation, and upregulation of BDNF are inhibited by antibodies against colony-stimulating factor 1 (CSF-1). Together, our results show that microglial CSF1 and BDNF signaling are indispensable for spinal LTP and chronic pain. The microglia-dependent transition of synaptic potentiation to structural alterations in pain pathways may underlie pain chronicity.