WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (71)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sung, B.
Right arrow Articles by Mao, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sung, B.
Right arrow Articles by Mao, J.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*GLUTAMIC ACID HYDROCHLORIDE

 Previous Article  |  Next Article 

The Journal of Neuroscience, April 1, 2003, 23(7):2899

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

Backil Sung, Grewo Lim, and Jianren Mao

Massachusetts General Hospital Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

The central glutamatergic system has been implicated in the pathogenesis of neuropathic pain, and a highly active central glutamate transporter (GT) system regulates the uptake of endogenous glutamate. Here we demonstrate that both the expression and uptake activity of spinal GTs changed after chronic constriction nerve injury (CCI) and contributed to neuropathic pain behaviors in rats. CCI induced an initial GT upregulation up to at least postoperative day 5 primarily within the ipsilateral spinal cord dorsal horn, which was followed by a GT downregulation when examined on postoperative days 7 and 14 by Western blot and immunohistochemistry. Intrathecal administration of the tyrosine kinase receptor inhibitor K252a and the mitogen-activated protein kinase inhibitor PD98059 for postoperative days 1-4 reduced and nearly abolished the initial GT upregulation in CCI rats, respectively. Prevention of the CCI-induced GT upregulation by PD98059 resulted in exacerbated thermal hyperalgesia and mechanical allodynia reversible by the noncompetitive NMDA receptor antagonist MK-801, indicating that the initial GT upregulation hampered the development of neuropathic pain behaviors. Moreover, CCI significantly reduced glutamate uptake activity of spinal GTs when examined on postoperative day 5, which was prevented by riluzole (a positive GT activity regulator) given intrathecally twice a day for postoperative days 1-4. Consistently, riluzole attenuated and gradually reversed neuropathic pain behaviors when the 4 d riluzole treatment was given for postoperative days 1-4 and 5-8, respectively. These results indicate that changes in the expression and glutamate uptake activity of spinal GTs may play a critical role in both the induction and maintenance of neuropathic pain after nerve injury via the regulation of regional glutamate homeostasis, a new mechanism relevant to the pathogenesis of neuropathic pain.

Key words: neuropathic pain; allodynia; hyperalgesia; glutamate transporter; nerve injury; riluzole; tyrosine kinase; mitogen-activated protein kinase

Copyright © 2003 Society for Neuroscience  0270-6474/03/2372899-12$05.00/0


This article has been cited by other articles:


Home page
 NeuroscientistHome page
P. T. Ohara, J.-P. Vit, A. Bhargava, M. Romero, C. Sundberg, A. C. Charles, and L. Jasmin
Gliopathic Pain: When Satellite Glial Cells Go Bad
Neuroscientist, October 1, 2009; 15(5): 450 - 463.
[Abstract] [PDF]

Home page
 J. Neurophysiol.Home page
H. Nie and H.-R. Weng
Glutamate Transporters Prevent Excessive Activation of NMDA Receptors and Extrasynaptic Glutamate Spillover in the Spinal Dorsal Horn
J Neurophysiol, April 1, 2009; 101(4): 2041 - 2051.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
F. Wei, W. Guo, S. Zou, K. Ren, and R. Dubner
Supraspinal Glial-Neuronal Interactions Contribute to Descending Pain Facilitation
J. Neurosci., October 15, 2008; 28(42): 10482 - 10495.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Yang, S. Wang, B. Sung, G. Lim, and J. Mao
Morphine Induces Ubiquitin-Proteasome Activity and Glutamate Transporter Degradation
J. Biol. Chem., August 1, 2008; 283(31): 21703 - 21713.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. M. Ramer, L. T. McPhail, J. F. Borisoff, L. J. J. Soril, T. K. Y. Kaan, J. H. T. Lee, J. W. T. Saunders, L. P. R. Hwi, and M. S. Ramer
Endogenous TrkB Ligands Suppress Functional Mechanosensory Plasticity in the Deafferented Spinal Cord
J. Neurosci., May 23, 2007; 27(21): 5812 - 5822.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
V. L. Tawfik, M. L. LaCroix-Fralish, N. Nutile-McMenemy, and J. A. DeLeo
Transcriptional and Translational Regulation of Glial Activation by Morphine in a Rodent Model of Neuropathic Pain
J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1239 - 1247.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
R.-R. Ji and G. Strichartz
Cell Signaling and the Genesis of Neuropathic Pain
Sci. Signal., September 28, 2004; 2004(252): re14 - re14.
[Abstract] [Full Text] [PDF]


-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-