White Fletcher A, Feldman Polina, Miller Richard J
Cell Biology, Neurobiology & Anatomy, and Anesthesiology, Loyola University, Stritch School of Medicine, Chicago, IL 60611, USA.
Mol Interv. 2009 Aug;9(4):188-95. doi: 10.1124/mi.9.4.7.
Chemokines and chemokine receptors are widely expressed in the nervous system, where they play roles in the regulation of stem cell migration, axonal path finding, and neurotransmission. Chemokine signaling is also of key importance in the regulation of neuroinflammatory responses. The expression of the chemokine monocyte chemoattractant protein 1 (MCP1) and its receptor (CCR2) is upregulated by dorsal root ganglia neurons in rodent models of neuropathic pain. MCP1 increases the excitability of nociceptive neurons after a peripheral nerve injury, and disruption of MCP1 signaling blocks the development of neuropathic pain. In the spinal cord, microglial cells expressing CCR2 are thought to play an active role in the initiation and maintenance of pain hypersensitivity, and MCP1 may also alter the excitability of spinal neurons in some cases. Other predominant sites of CCR2 activation are found in the peripheral nervous system, thereby explaining, at least in some circumstances, the rapid anti-nociceptive effects of peripherally administered CCR2 antagonists. In this article we discuss the relative roles of CCR2 activation in the peripheral and central nervous systems in relation to the phenomenon of neuropathic pain.
趋化因子和趋化因子受体在神经系统中广泛表达，它们在干细胞迁移、轴突寻路和神经传递的调节中发挥作用。趋化因子信号传导在神经炎症反应的调节中也至关重要。在神经性疼痛的啮齿动物模型中，背根神经节神经元会上调趋化因子单核细胞趋化蛋白1（MCP1）及其受体（CCR2）的表达。MCP1会增加外周神经损伤后伤害性神经元的兴奋性，而MCP1信号传导的中断会阻止神经性疼痛的发展。在脊髓中，表达CCR2的小胶质细胞被认为在疼痛超敏反应的起始和维持中起积极作用，并且在某些情况下MCP1也可能改变脊髓神经元的兴奋性。CCR2激活的其他主要部位存在于外周神经系统中，从而至少在某些情况下解释了外周给予CCR2拮抗剂的快速抗伤害感受作用。在本文中，我们讨论了CCR2激活在周围和中枢神经系统中与神经性疼痛现象相关的相对作用。
