| RRC ID |
4747
|
| 著者 |
Jung H, Bhangoo S, Banisadr G, Freitag C, Ren D, White FA, Miller RJ.
|
| タイトル |
Visualization of chemokine receptor activation in transgenic mice reveals peripheral activation of CCR2 receptors in states of neuropathic pain.
|
| ジャーナル |
J Neurosci
|
| Abstract |
CCR2 chemokine receptor signaling has been implicated in the generation of diverse types of neuropathology, including neuropathic pain. For example, ccr2 knock-out mice are resistant to the establishment of neuropathic pain, and mice overexpressing its ligand, monocyte chemoattractant protein-1 (MCP1; also known as CCL2), show enhanced pain sensitivity. However, whether CCR2 receptor activation occurs in the central or peripheral nervous system in states of neuropathic pain has not been clear. We developed a novel method for visualizing CCR2 receptor activation in vivo by generating bitransgenic reporter mice in which the chemokine receptor CCR2 and its ligand MCP1 were labeled by the fluorescent proteins enhanced green fluorescent protein and monomeric red fluorescent protein-1, respectively. CCR2 receptor activation under conditions such as acute inflammation and experimental autoimmune encephalomyelitis could be faithfully visualized by using these mice. We examined the status of CCR2 receptor activation in a demyelination injury model of neuropathic pain and found that MCP1-induced CCR2 receptor activation mainly occurred in the peripheral nervous system, including the injured peripheral nerve and dorsal root ganglia. These data explain the rapid antinociceptive effects of peripherally administered CCR2 antagonists under these circumstances, suggesting that CCR2 antagonists may ameliorate pain by inhibiting CCR2 receptor activation in the periphery. The method developed here for visualizing CCR2 receptor activation in vivo may be extended to G-protein-coupled receptors (GPCRs) in general and will be valuable for studying intercellular GPCR-mediated communication in vivo.
|
| 巻・号 |
29(25)
|
| ページ |
8051-62
|
| 公開日 |
2009-6-24
|
| DOI |
10.1523/JNEUROSCI.0485-09.2009
|
| PII |
29/25/8051
|
| PMID |
19553445
|
| PMC |
PMC3097108
|
| MeSH |
Animals
Cells, Cultured
Chemokine CCL2 / deficiency
Chemokine CCL2 / genetics
Chemokine CCL2 / metabolism*
Demyelinating Diseases / chemically induced
Disease Models, Animal
Female
Ganglia, Spinal / drug effects
Ganglia, Spinal / metabolism
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Immunohistochemistry
In Situ Hybridization
Lipopolysaccharides / administration & dosage
Lipopolysaccharides / pharmacology
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Mice
Mice, Transgenic
Neurons / drug effects
Neurons / metabolism*
Pain / genetics
Pain / metabolism*
Pain Measurement / methods
Pain Threshold / psychology
Peripheral Nerves / drug effects
Peripheral Nerves / metabolism*
Polymerase Chain Reaction
Receptors, CCR2 / deficiency
Receptors, CCR2 / genetics
Receptors, CCR2 / metabolism*
Sciatic Neuropathy / chemically induced
Transfection
|
| IF |
5.674
|
| 引用数 |
100
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| 遺伝子材料 |
MSM Mouse BAC (RDB04214) MSMg01-529G05 |
