Chemokine signaling and the management of neuropathic pain.
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.
White
Fletcher A
FA
Cell Biology, Neurobiology & Anatomy, and Anesthesiology, Loyola University, Stritch School of Medicine, Chicago, IL 60611, USA. fwhite@lumc.edu
Feldman
Polina
P
Miller
Richard J
RJ
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D018932:Chemokine CCL2; D054390:Receptors, CCR2