PMID- 25555372
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20220408
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1599
DP  - 2015 Mar 2
TI  - MCP-1 stimulates spinal microglia via PI3K/Akt pathway in bone cancer pain.
PG  - 158-67
LID - S0006-8993(14)01750-8 [pii]
LID - 10.1016/j.brainres.2014.12.043 [doi]
AB  - Accumulating evidence suggests that chemokine monocyte chemoattractant protein-1 
      (MCP-1) is significantly involved in the activation of spinal microglia 
      associated with pathological pain, at the same time that the phosphatidylinositol 
      3-kinase/Protein Kinase B (PI3K/Akt) pathway localized in spinal microglia is 
      involved in both neuropathic and inflammatory pain. However, whether there is a 
      connection between MCP-1 and the PI3K/Akt pathway and in their underlying 
      mechanisms in bone cancer pain (BCP) has not yet been elucidated. In the current 
      study, we investigated the expression changes of p-Akt in microglia and OX-42 
      (microglia marker) after being stimulated with MCP-1 in vitro, as well as in a 
      BCP model that was established by an intramedullary injection of mammary gland 
      carcinoma cells(Walker 256 cells) into the tibia of rats. We observed a 
      significant increase in expression levels of p-Akt and OX-42 in microglia as well 
      as in spinal dorsal horns of BCP rats. Furthermore, the intrathecal 
      administration of an anti-MCP-1 neutralizing antibody or PI3K inhibitor LY294002 
      reduced the expression of p-Akt or OX-42, and LY294002 attenuated the mechanical 
      allodynia of BCP rats. These results suggest that MCP-1 may stimulate spinal 
      microglia via the PI3K/Akt pathway in BCP.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Jin, Di
AU  - Jin D
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215006, China. Electronic address: 
      kame_jindi@163.com.
FAU - Yang, Jian-Ping
AU  - Yang JP
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215006, China. Electronic address: 
      szyangjp@suda.edu.cn.
FAU - Hu, Ji-Hua
AU  - Hu JH
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215006, China. Electronic address: szhujh30@163.com.
FAU - Wang, Li-Na
AU  - Wang LN
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215006, China. Electronic address: 
      lenawang0303@163.com.
FAU - Zuo, Jian-Ling
AU  - Zuo JL
AD  - Brain Research Laboratory, The First Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu 215006, China. Electronic address: jzuo919@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141231
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/pathology/*physiopathology
MH  - Carcinoma, Ductal, Breast/pathology/physiopathology
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/antagonists & inhibitors/*metabolism
MH  - Chromones/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Hyperalgesia/drug therapy/pathology/physiopathology
MH  - Microglia/drug effects/pathology/*physiology
MH  - Morpholines/pharmacology
MH  - Neoplasm Transplantation
MH  - Pain/drug therapy/pathology/*physiopathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Posterior Horn Cells/drug effects/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction/drug effects
MH  - Tibia
OTO - NOTNLM
OT  - Bone cancer pain
OT  - MCP-1
OT  - Microglia
OT  - PI3K
OT  - Spine
EDAT- 2015/01/04 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/01/04 06:00
PHST- 2014/10/28 00:00 [received]
PHST- 2014/12/19 00:00 [revised]
PHST- 2014/12/21 00:00 [accepted]
PHST- 2015/01/04 06:00 [entrez]
PHST- 2015/01/04 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0006-8993(14)01750-8 [pii]
AID - 10.1016/j.brainres.2014.12.043 [doi]
PST - ppublish
SO  - Brain Res. 2015 Mar 2;1599:158-67. doi: 10.1016/j.brainres.2014.12.043. Epub 2014 
      Dec 31.