PMID- 20737477
OWN - NLM
STAT- MEDLINE
DCOM- 20110126
LR  - 20211020
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 58
IP  - 15
DP  - 2010 Nov 15
TI  - Spinal injection of TNF-alpha-activated astrocytes produces persistent pain symptom 
      mechanical allodynia by releasing monocyte chemoattractant protein-1.
PG  - 1871-80
LID - 10.1002/glia.21056 [doi]
AB  - Accumulating evidence suggests that spinal astrocytes play an important role in 
      the genesis of persistent pain, by increasing the activity of spinal cord 
      nociceptive neurons, i.e., central sensitization. However, direct evidence of 
      whether activation of astrocytes is sufficient to induce chronic pain symptoms is 
      lacking. We investigated whether and how spinal injection of activated astrocytes 
      could produce mechanical allodynia, a cardinal feature of chronic pain, in naive 
      mice. Spinal (intrathecal) injection of astrocytes, which were prepared from 
      cerebral cortexes of neonatal mice and briefly stimulated by tumor necrosis 
      factor-alpha (TNF-alpha), induced a substantial decrease in paw withdrawal 
      thresholds, indicating the development of mechanical allodynia. This allodynia 
      was prevented when the astrocyte cultures were pretreated with a peptide 
      inhibitor of c-Jun N-terminal kinase (JNK), D-JNKI-1. Of note a short exposure of 
      astrocytes to TNF-alpha for 15 min dramatically increased the expression and release 
      of the chemokine monocyte chemoattractant protein-1 (MCP-1), even 3 h after TNF-alpha 
      withdrawal, in a JNK-dependent manner. In parallel, intrathecal administration of 
      TNF-alpha induced MCP-1 expression in spinal cord astrocytes. In particular, 
      mechanical allodynia induced by TNF-alpha-activated astrocytes was reversed by a 
      MCP-1 neutralizing antibody. Finally, pretreatment of astrocytes with MCP-1 siRNA 
      attenuated astrocytes-induced mechanical allodynia. Taken together, our results 
      suggest that activated astrocytes are sufficient to produce persistent pain 
      symptom in naive mice by releasing MCP-1.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Gao, Yong-Jing
AU  - Gao YJ
AD  - Sensory Plasticity Laboratory, Department of Anesthesiology, Brigham and Women's 
      Hospital and Harvard Medical School, Pain Research Center, Boston, Massachusetts 
      02115, USA. yjing@zeus.bwh.harvard.edu
FAU - Zhang, Ling
AU  - Zhang L
FAU - Ji, Ru-Rong
AU  - Ji RR
LA  - eng
GR  - R01 NS054932/NS/NINDS NIH HHS/United States
GR  - NS67686/NS/NINDS NIH HHS/United States
GR  - R01 DE017794-04/DE/NIDCR NIH HHS/United States
GR  - R01 NS067686/NS/NINDS NIH HHS/United States
GR  - DE17794/DE/NIDCR NIH HHS/United States
GR  - R01 NS054932-03/NS/NINDS NIH HHS/United States
GR  - R01 DE017794-05/DE/NIDCR NIH HHS/United States
GR  - R01 DE017794/DE/NIDCR NIH HHS/United States
GR  - NS54932/NS/NINDS NIH HHS/United States
GR  - R01 NS054932-04/NS/NINDS NIH HHS/United States
GR  - R01 NS067686-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Aif1 protein, mouse)
RN  - 0 (Antibodies)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Microfilament Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tnfrh2 protein, mouse)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies/therapeutic use
MH  - Astrocytes/*drug effects/metabolism
MH  - Calcium-Binding Proteins/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Chemokine CCL2/immunology/*metabolism
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Gene Expression Regulation/*drug effects
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hyperalgesia/*chemically induced/drug therapy/pathology
MH  - Injections, Spinal/methods
MH  - MAP Kinase Kinase 4/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microfilament Proteins
MH  - Pain Threshold/drug effects
MH  - RNA, Small Interfering/therapeutic use
MH  - Receptors, Tumor Necrosis Factor/deficiency
MH  - Receptors, Tumor Necrosis Factor, Type I/deficiency
MH  - Spinal Cord/*pathology
MH  - Tumor Necrosis Factor-alpha/*adverse effects
PMC - PMC2951489
MID - NIHMS219768
EDAT- 2010/08/26 06:00
MHDA- 2011/01/28 06:00
PMCR- 2011/11/15
CRDT- 2010/08/26 06:00
PHST- 2010/08/26 06:00 [entrez]
PHST- 2010/08/26 06:00 [pubmed]
PHST- 2011/01/28 06:00 [medline]
PHST- 2011/11/15 00:00 [pmc-release]
AID - 10.1002/glia.21056 [doi]
PST - ppublish
SO  - Glia. 2010 Nov 15;58(15):1871-80. doi: 10.1002/glia.21056.