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

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

Research output: Contribution to journalArticle

156 Citations (Scopus)

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
Externally publishedYes

Fingerprint

CCR2 Receptors
Chemokine CCL2
Spinal Ganglia
Neurons
Neurotransmitter Agents
Nociceptors
Neuralgia
Peripheral Nerve Injuries
Chemokine CCL1
Transient Receptor Potential Channels
Afferent Neurons
Secretory Vesicles
Carisoprodol
Demyelinating Diseases
Sensory Receptor Cells
Chemokines
Transcriptional Activation
Rodentia
Depolarization
Pain

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

Cite this

Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. / Jung, Hosung; Toth, Peter T.; White, Fletcher; Miller, Richard J.

In: Journal of Neurochemistry, Vol. 104, No. 1, 01.2008, p. 254-263.

Research output: Contribution to journalArticle

Jung, Hosung ; Toth, Peter T. ; White, Fletcher ; Miller, Richard J. / Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. In: Journal of Neurochemistry. 2008 ; Vol. 104, No. 1. pp. 254-263.
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