PMID- 19553445
OWN - NLM
STAT- MEDLINE
DCOM- 20090804
LR  - 20231213
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 29
IP  - 25
DP  - 2009 Jun 24
TI  - Visualization of chemokine receptor activation in transgenic mice reveals 
      peripheral activation of CCR2 receptors in states of neuropathic pain.
PG  - 8051-62
LID - 10.1523/JNEUROSCI.0485-09.2009 [doi]
AB  - 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.
FAU - Jung, Hosung
AU  - Jung H
AD  - Department of Molecular Pharmacology and Biological Chemistry, Northwestern 
      University, Chicago, Illinois 60611, USA.
FAU - Bhangoo, Sonia
AU  - Bhangoo S
FAU - Banisadr, Ghazal
AU  - Banisadr G
FAU - Freitag, Caroline
AU  - Freitag C
FAU - Ren, Dongjun
AU  - Ren D
FAU - White, Fletcher A
AU  - White FA
FAU - Miller, Richard J
AU  - Miller RJ
LA  - eng
GR  - R01 DA026040/DA/NIDA NIH HHS/United States
GR  - R01 NS049136-03/NS/NINDS NIH HHS/United States
GR  - R01 NS049136/NS/NINDS NIH HHS/United States
GR  - R01 DA013141-06A2/DA/NIDA NIH HHS/United States
GR  - R01 DA026040-01/DA/NIDA NIH HHS/United States
GR  - R01 DA013141/DA/NIDA NIH HHS/United States
GR  - R01 DA026040-02/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Receptors, CCR2)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/deficiency/genetics/*metabolism
MH  - Demyelinating Diseases/chemically induced
MH  - Disease Models, Animal
MH  - Female
MH  - Ganglia, Spinal/drug effects/metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Lipopolysaccharides/administration & dosage/pharmacology
MH  - Luminescent Proteins/genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Neurons/drug effects/*metabolism
MH  - Pain/genetics/*metabolism
MH  - Pain Measurement/methods
MH  - Pain Threshold/psychology
MH  - Peripheral Nerves/drug effects/*metabolism
MH  - Polymerase Chain Reaction
MH  - Receptors, CCR2/deficiency/genetics/*metabolism
MH  - Sciatic Neuropathy/chemically induced
MH  - Transfection
MH  - Red Fluorescent Protein
PMC - PMC3097108
MID - NIHMS144934
EDAT- 2009/06/26 09:00
MHDA- 2009/08/06 09:00
PMCR- 2009/12/24
CRDT- 2009/06/26 09:00
PHST- 2009/06/26 09:00 [entrez]
PHST- 2009/06/26 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
PHST- 2009/12/24 00:00 [pmc-release]
AID - 29/25/8051 [pii]
AID - 3497239 [pii]
AID - 10.1523/JNEUROSCI.0485-09.2009 [doi]
PST - ppublish
SO  - J Neurosci. 2009 Jun 24;29(25):8051-62. doi: 10.1523/JNEUROSCI.0485-09.2009.