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Monocyte chemoattractant protein‐1 functions as a neuromodulator in dorsal root ganglia neurons
Author(s) -
Jung Hosung,
Toth Peter T.,
White Fletcher A.,
Miller Richard J.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04969.x
Subject(s) - nociceptor , dorsal root ganglion , ccr2 , trpv1 , neuroscience , microbiology and biotechnology , chemistry , neuropathic pain , chemokine receptor , receptor , chemokine , biology , medicine , transient receptor potential channel , nociception , sensory system
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.