rdf:type |
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0027796,
umls-concept:C0027882,
umls-concept:C0037925,
umls-concept:C0161479,
umls-concept:C0185117,
umls-concept:C0253876,
umls-concept:C1444748,
umls-concept:C1517945,
umls-concept:C1527148,
umls-concept:C1880177,
umls-concept:C2911684
|
pubmed:issue |
4
|
pubmed:dateCreated |
2011-5-16
|
pubmed:abstractText |
Nerve injury leads to sensitization mechanisms in the peripheral and central nervous system which involve transcriptional and post-transcriptional modifications in sensory nerves. To assess protein regulations in the spinal cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE) technology. Among approximately 2300 protein spots separated on each gel we detected 55 significantly regulated proteins after SNI whereof 41 were successfully identified by MALDI-TOF MS. Out of the proteins which were regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A inhibitor latexin because protease dysfunctions contribute to the development of neuropathic pain. Latexin protein expression was reduced after SNI which could be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ hybridisation. The decrease of latexin was associated with an increase of the activity of carboxypeptidase A indicating that the balance between latexin and carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury due to a loss of latexin expression in spinal cord neurons. This may contribute to the development of cold allodynia because normalization of neuronal latexin expression in the spinal cord by AAV-mediated latexin transduction or administration of a small molecule carboxypeptidase A inhibitor significantly reduced acetone-evoked nociceptive behavior after SNI. Our results show the usefulness of proteomics as a screening tool to identify novel mechanisms of nerve injury evoked hypernociception and suggest that carboxypeptidase A inhibition might be useful to reduce cold allodynia.
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pubmed:commentsCorrections |
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21572518-9729242
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:issn |
1932-6203
|
pubmed:author |
pubmed-author:BeckhausTobiasT,
pubmed-author:EhnertCorinaC,
pubmed-author:FauthMarkusM,
pubmed-author:GeisslingerGerdG,
pubmed-author:HäusslerAnnettA,
pubmed-author:JennesIngoI,
pubmed-author:KühleinHilmar NilsHN,
pubmed-author:KarasMichaelM,
pubmed-author:LimHee-YoungHY,
pubmed-author:MöserChristineC,
pubmed-author:MarschalekRolfR,
pubmed-author:NiederbergerEllenE,
pubmed-author:SpiethKatharinaK,
pubmed-author:TegederIrmgardI
|
pubmed:copyrightInfo |
© 2011 Kühlein et al.
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pubmed:issnType |
Electronic
|
pubmed:volume |
6
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
e19270
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pubmed:meshHeading |
pubmed-meshheading:21572518-Animals,
pubmed-meshheading:21572518-Mice,
pubmed-meshheading:21572518-Antigens,
pubmed-meshheading:21572518-Sciatic Nerve,
pubmed-meshheading:21572518-Spinal Cord,
pubmed-meshheading:21572518-Rats,
pubmed-meshheading:21572518-Neurons,
pubmed-meshheading:21572518-Cold Temperature,
pubmed-meshheading:21572518-Neuralgia,
pubmed-meshheading:21572518-Succinates,
pubmed-meshheading:21572518-Male,
pubmed-meshheading:21572518-Adenoviridae,
pubmed-meshheading:21572518-Sciatic Neuropathy,
pubmed-meshheading:21572518-Rats, Sprague-Dawley,
pubmed-meshheading:21572518-Mice, Inbred C57BL,
pubmed-meshheading:21572518-Electrophoresis, Gel, Two-Dimensional,
pubmed-meshheading:21572518-Sural Nerve
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