TY  - JOUR
A1  - Kühlein, Hilmar Nils
A1  - Tegeder, Irmgard
A1  - Möser, Christine Verena
A1  - Lim, Hee-Young
A1  - Häussler, Annett
A1  - Spieth, Katharina
A1  - Jennes, Ingo Wilhelm Matthias
A1  - Marschalek, Rolf
A1  - Beckhaus, Tobias
A1  - Karas, Michael
A1  - Fauth, Markus
A1  - Ehnert, Corina
A1  - Geisslinger, Gerd
A1  - Niederberger, Ellen
T1  - Nerve injury evoked loss of latexin expression in spinal cord neurons contributes to the development of neuropathic pain
T2  - PLoS One
N2  - 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.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22547
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-114022
SN  - 1932-6203
N1  - Copyright: © 2011 Kühlein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 6
IS  - (4): e19270
SP  - 1
EP  - 11
PB  - PLoS
CY  - Lawrence, Kan.
ER  -