Document Detail


Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain.
MedLine Citation:
PMID:  20542084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain.
Authors:
Romain-Daniel Gosselin; Damien Bebber; Isabelle Decosterd
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-11
Journal Detail:
Title:  Neuroscience letters     Volume:  480     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-13     Completed Date:  2010-10-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  132-7     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Pain Research Unit, Department of Anesthesiology, University Hospital Center and University of Lausanne, Bugnon 46, 1011 Lausanne, Switzerland. Romain-Daniel.Gosselin@chuv.ch
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport System X-AG / biosynthesis
Animals
Astrocytes / metabolism
Biological Transport
Excitatory Amino Acid Transporter 1 / biosynthesis
Excitatory Amino Acid Transporter 2 / biosynthesis
GABA Plasma Membrane Transport Proteins / biosynthesis*
Medulla Oblongata / metabolism*
Microglia / metabolism
Pain / etiology,  metabolism*
Peripheral Nervous System Diseases / etiology,  metabolism*
Peroneal Nerve / injuries
Rats
Rats, Sprague-Dawley
Synaptosomes / metabolism
Tibial Nerve / injuries
gamma-Aminobutyric Acid / metabolism
Chemical
Reg. No./Substance:
0/Amino Acid Transport System X-AG; 0/Excitatory Amino Acid Transporter 1; 0/Excitatory Amino Acid Transporter 2; 0/GABA Plasma Membrane Transport Proteins; 0/Slc6a1 protein, rat; 0/Slc6a11 protein, rat; 56-12-2/gamma-Aminobutyric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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