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

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Gao, Y-J; Ji, R-R

Published Date

  • April 2010

Published In

Volume / Issue

  • 126 / 1

Start / End Page

  • 56 - 68

PubMed ID

  • 20117131

Pubmed Central ID

  • 20117131

Electronic International Standard Serial Number (EISSN)

  • 1879-016X

Digital Object Identifier (DOI)

  • 10.1016/j.pharmthera.2010.01.002

Language

  • eng

Conference Location

  • England