Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain

被引：179

作者：

Zhou, Li-Jun ^{[1
,2
,3
,4
]}

Peng, Jiyun ^{[3
,5
]}

Xu, Ya-Nan ^{[1
,2
]}

Zeng, Wei-Jie ^{[1
,2
]}

Zhang, Jun ^{[1
,2
]}

Wei, Xiao ^{[1
,2
]}

Mai, Chun-Lin ^{[1
,2
]}

Lin, Zhen-Jia ^{[1
,2
]}

Liu, Yong ^{[3
,5
]}

Murugan, Madhuvika ^{[3
,5
]}

Eyo, Ukpong B. ^{[3
,5
]}

Umpierre, Anthony D. ^{[5
]}

Xin, Wen-Jun ^{[1
,2
,4
]}

Chen, Tao ^{[6
,7
]}

Li, Mingtao ^{[4
]}

Wang, Hui ^{[8
,9
]}

Richardson, Jason R. ^{[10
]}

Tan, Zhi ^{[1
,2
]}

Liu, Xian-Guo ^{[1
,2
,4
]}

Wu, Long-Jun ^{[3
,5
,11
,12
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Physiol, Guangzhou 510080, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Zhongshan Sch Med, Pain Res Ctr, Guangzhou 510080, Guangdong, Peoples R China

[3] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA

[4] Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou 510080, Guangdong, Peoples R China

[5] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA

[6] Fourth Mil Med Univ, Dept Anat Histol & Embryol, Xian 710032, Shaanxi, Peoples R China

[7] Fourth Mil Med Univ, KK Leung Brain Res Ctr, Xian 710032, Shaanxi, Peoples R China

[8] Rutgers Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA

[9] Nantong Univ, Sch Pharm, Dept Pharmacol, Nantong 22600, Peoples R China

[10] Florida Int Univ, Dept Environm Hlth Sci, Miami, FL 33199 USA

[11] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[12] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA

来源：

CELL REPORTS | 2019年 / 27卷 / 13期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

LONG-TERM POTENTIATION; FIBER-EVOKED POTENTIALS; GENE-RELATED PEPTIDE; NEUROTROPHIC FACTOR; ROOT GANGLIA; KAPPA-B; CORD; HYPERSENSITIVITY; ACTIVATION; MODEL;

D O I：

10.1016/j.celrep.2019.05.087

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3844 / +

页数：22

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