PMID- 20880510
OWN - NLM
STAT- MEDLINE
DCOM- 20110124
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 7
IP  - 4
DP  - 2010 Oct
TI  - Targeting astrocyte signaling for chronic pain.
PG  - 482-93
LID - 10.1016/j.nurt.2010.05.016 [doi]
AB  - Clinical management of chronic pain after nerve injury (neuropathic pain) and 
      tumor invasion (cancer pain) is a real challenge due to our limited understanding 
      of the cellular mechanisms that initiate and maintain chronic pain. It has been 
      increasingly recognized that glial cells, such as microglia and astrocytes in the 
      CNS play an important role in the development and maintenance of chronic pain. 
      Notably, astrocytes make very close contacts with synapses and astrocyte reaction 
      after nerve injury, arthritis, and tumor growth is more persistent than 
      microglial reaction, and displays a better correlation with chronic pain 
      behaviors. Accumulating evidence indicates that activated astrocytes can release 
      pro-inflammatory cytokines (e.g., interleukin [IL]-1beta) and chemokines (e.g., 
      monocyte chemoattractant protein-1 [MCP-1]/also called CCL2) in the spinal cord 
      to enhance and prolong persistent pain states. IL-1beta can powerfully modulate 
      synaptic transmission in the spinal cord by enhancing excitatory synaptic 
      transmission and suppressing inhibitory synaptic transmission. IL-1beta activation 
      (cleavage) in the spinal cord after nerve injury requires the matrix 
      metalloprotease-2. In particular, nerve injury and inflammation activate the 
      c-Jun N-terminal kinase in spinal astrocytes, leading to a substantial increase 
      in the expression and release of MCP-1. The MCP-1 increases pain sensitivity via 
      direct activation of NMDA receptors in dorsal horn neurons. Pharmacological 
      inhibition of the IL-1beta, c-Jun N-terminal kinase, MCP-1, or matrix 
      metalloprotease-2 signaling via spinal administration has been shown to attenuate 
      inflammatory, neuropathic, or cancer pain. Therefore, interventions in specific 
      signaling pathways in astrocytes may offer new approaches for the management of 
      chronic pain.
CI  - Copyright (c) 2010 The American Society for Experimental NeuroTherapeutics, Inc. 
      Published by Elsevier Inc. All rights reserved.
FAU - Gao, Yong-Jing
AU  - Gao YJ
AD  - Department of Anesthesiology, Sensory Plasticity Laboratory, Pain Research 
      Center, Brigham and Women's Hospital and Harvard Medical School, Boston, 
      Massachusetts 02115, USA. yjing@zeus.bwh.harvard.edu
FAU - Ji, Ru-Rong
AU  - Ji RR
LA  - eng
GR  - R01 NS054932/NS/NINDS NIH HHS/United States
GR  - R01 DE017794-04/DE/NIDCR NIH HHS/United States
GR  - R01 DE017794/DE/NIDCR NIH HHS/United States
GR  - R01 NS067686/NS/NINDS NIH HHS/United States
GR  - R01 NS67686/NS/NINDS 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 NS067686-02/NS/NINDS NIH HHS/United States
GR  - R01 NS54932/NS/NINDS NIH HHS/United States
GR  - R01 DE17794/DE/NIDCR 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
PT  - Review
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Astrocytes/pathology/*physiology
MH  - Chronic Disease
MH  - Cytokines/genetics/metabolism
MH  - Humans
MH  - Inflammation/etiology/metabolism/pathology
MH  - MAP Kinase Signaling System/physiology
MH  - Pain/*pathology
MH  - *Pain Management
PMC - PMC2950097
MID - NIHMS213544
EDAT- 2010/10/01 06:00
MHDA- 2011/01/25 06:00
PMCR- 2011/10/01
CRDT- 2010/10/01 06:00
PHST- 2010/03/07 00:00 [received]
PHST- 2010/05/18 00:00 [revised]
PHST- 2010/05/19 00:00 [accepted]
PHST- 2010/10/01 06:00 [entrez]
PHST- 2010/10/01 06:00 [pubmed]
PHST- 2011/01/25 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - S1878-7479(23)00202-7 [pii]
AID - 70400482 [pii]
AID - 10.1016/j.nurt.2010.05.016 [doi]
PST - ppublish
SO  - Neurotherapeutics. 2010 Oct;7(4):482-93. doi: 10.1016/j.nurt.2010.05.016.