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Pharmacol Ther. 2010 Apr;126(1):56-68. doi: 10.1016/j.pharmthera.2010.01.002. Epub 2010 Feb 1.

Chemokines, neuronal-glial interactions, and central processing of neuropathic pain.

Author information

  • 1Pain Research Center, Department of Anesthesiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States. yjing@zeus.bwh.harvard.edu

Abstract

Millions of people worldwide suffer from neuropathic pain as a result of damage to or dysfunction of the nervous system under various disease conditions. Development of effective therapeutic strategies requires a better understanding of molecular and cellular mechanisms underlying the pathogenesis of neuropathic pain. It has been increasingly recognized that spinal cord glial cells such as microglia and astrocytes play a critical role in the induction and maintenance of neuropathic pain by releasing powerful neuromodulators such as proinflammatory cytokines and chemokines. Recent evidence reveals chemokines as new players in pain control. In this article, we review evidence for chemokine modulation of pain via neuronal-glial interactions by focusing on the central role of two chemokines, CX3CL1 (fractalkine) and CCL2 (MCP-1), because they differentially regulate neuronal-glial interactions. Release of CX3CL1 from neurons is ideal to mediate neuronal-to-microglial signaling, since the sole receptor of this chemokine, CX3CR1, is expressed in spinal microglia and activation of the receptor leads to phosphorylation of p38 MAP kinase in microglia. Although CCL2 was implicated in neuronal-to-microglial signaling, a recent study shows a novel role of CCL2 in astroglial-to-neuronal signaling after nerve injury. In particular, CCL2 rapidly induces central sensitization by increasing the activity of NMDA receptors in dorsal horn neurons. Insights into the role of chemokines in neuronal-glial interactions after nerve injury will identify new targets for therapeutic intervention of neuropathic pain.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID:
20117131
[PubMed - indexed for MEDLINE]
PMCID:
PMC2839017
Free PMC Article

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