RRC ID |
3815
|
著者 |
Jung H, Toth PT, White FA, Miller RJ.
|
タイトル |
Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons.
|
ジャーナル |
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.
|
巻・号 |
104(1)
|
ページ |
254-63
|
公開日 |
2008-1-1
|
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 |
4.066
|
引用数 |
151
|
WOS 分野
|
NEUROSCIENCES
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
遺伝子材料 |
MSM Mouse BAC (RDB04214) MSMg01-529G05 |