Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons

Hosung Jung, Peter T. Toth, Fletcher A. White, Richard J. Miller

Research output: Contribution to journalArticle

169 Scopus citations

Abstract

It has previously been observed that expression of chemokine monocyte chemoattractant protein-1 (MCP-1/CC chemokine ligand 2 (CCL2)) and its receptor CC chemokine receptor 2 (CCR2) is up-regulated by dorsal root ganglion (DRG) neurons in association with rodent models of neuropathic pain. MCP-1 increases the excitability of nociceptive neurons after a peripheral nerve injury, while disruption of MCP-1/CCR2 signaling blocks the development of neuropathic pain, suggesting MCP-1 signaling is responsible for heightened pain sensitivity. To define the mechanisms of MCP-1 signaling in DRG, we studied intracellular processing, release, and receptor-mediated signaling of MCP-1 in DRG neurons. We found that in a focal demyelination model of neuropathic pain both MCP-1 and CCR2 were up-regulated by the same neurons including transient receptor potential vanilloid receptor subtype 1 (TRPV1) expressing nociceptors. MCP-1 expressed by DRG neurons was packaged into large dense-core vesicles whose release could be induced from the soma by depolarization in a Ca 2+-dependent manner. Activation of CCR2 by MCP-1 could sensitize nociceptors via transactivation of transient receptor potential channels. Our results suggest that MCP-1 and CCR2, up-regulated by sensory neurons following peripheral nerve injury, might participate in neural signal processing which contributes to sustained excitability of primary afferent neurons.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalJournal of Neurochemistry
Volume104
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Chemokine
  • Dorsal root ganglion
  • Neuropathic pain
  • Neurotransmitter
  • Transient receptor potential ankyrin 1
  • Transient receptor potential vanilloid receptor subtype 1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons'. Together they form a unique fingerprint.

  • Cite this