CCL2 is a key mediator of microglia activation in neuropathic pain states

被引:262
作者
Thacker, Michael A. [1 ,2 ]
Clark, Anna K. [1 ]
Bishop, Thomas [1 ]
Grist, John [1 ]
Yip, Ping K. [1 ]
Moon, Lawrence D. F. [1 ]
Thompson, Stephen W. N. [1 ]
Marchand, Fabien [1 ]
McMahon, Stephen B. [1 ,3 ]
机构
[1] Kings Coll London, Neurorestorat Grp, Wolfson Ctr Age Related Dis, London SE1 1UL, England
[2] Kings Coll London, Acad Dept Physiotherapy, London SE1 1UL, England
[3] London Pain Consortium, London, England
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
CCL2; Microglia; Neuropathic pain; Rat; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CCR2 CHEMOKINE RECEPTOR; DORSAL-ROOT GANGLIA; RAT SPINAL-CORD; EXPRESSION; MODEL; INHIBITION; MCP-1/CCL2; RELEASE; NEURONS;
D O I
10.1016/j.ejpain.2008.04.017
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
While neuroimmune interactions are increasingly recognized as important in nociceptive processing, the nature and functional significance of these interactions is not well defined. There are Multiple reports that the activation of spinal microglia is a critical event in the generation of neuropathic pain behaviors but the mediators of this activation remain disputed. Here we show that the chemokine CCL2. produced by both damaged and undamaged primary sensory neurons in neuropathic pain states in rats, is released in an activity dependent manner from the central terminals of these fibres. We also demonstrate that intraspinal CCL2 in naive rats leads to activation of spinal microglia and neuropathic pain-like behavior. An essential role for spinal CCL2 is demonstrated by the inhibition of neuropathic pain behavior and microglial activation by a specific neutralising antibody to CCL2 administered intrathecally. Thus, the neuronal expression of CCL2 provides a mechanism for immune activation, which in turn regulates the sensitivity of pain signaling systems in neuropathic pain states. (C) 2008 Published by Elsevier Ltd on behalf of European Federation of Chapters of the International Association for the Study of Pain.
引用
收藏
页码:263 / 272
页数:10
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