RRC ID 3815
Author Jung H, Toth PT, White FA, Miller RJ.
Title Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons.
Journal J. Neurochem.
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 Ca2+-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.
Volume 104(1)
Pages 254-63
Published 2008-1
DOI 10.1111/j.1471-4159.2007.04969.x
PII JNC4969
PMID 17944871
PMC PMC2186066
MeSH Animals Calcium / metabolism Capsaicin / pharmacology Cell Line, Transformed Chemokine CCL2 / metabolism Disease Models, Animal Drug Interactions Enzyme-Linked Immunosorbent Assay / methods Ganglia, Spinal / cytology* Gene Expression Regulation / physiology* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Mice Mice, Transgenic Neurons / drug effects Neurons / metabolism* Polysaccharides Receptors, CCR2 / genetics Receptors, CCR2 / physiology* Sciatic Neuropathy / chemically induced Sciatic Neuropathy / metabolism Transfection / methods
IF 4.609
Times Cited 122
WOS Category NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material MSM Mouse BAC (RDB04214) MSMg01-529G05