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Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain

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...

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Autores principales: Kühlein, Hilmar Nils, Tegeder, Irmgard, Möser, Christine, Lim, Hee-Young, Häussler, Annett, Spieth, Katharina, Jennes, Ingo, Marschalek, Rolf, Beckhaus, Tobias, Karas, Michael, Fauth, Markus, Ehnert, Corina, Geisslinger, Gerd, Niederberger, Ellen
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084808/
https://www.ncbi.nlm.nih.gov/pubmed/21572518
http://dx.doi.org/10.1371/journal.pone.0019270
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author Kühlein, Hilmar Nils
Tegeder, Irmgard
Möser, Christine
Lim, Hee-Young
Häussler, Annett
Spieth, Katharina
Jennes, Ingo
Marschalek, Rolf
Beckhaus, Tobias
Karas, Michael
Fauth, Markus
Ehnert, Corina
Geisslinger, Gerd
Niederberger, Ellen
author_facet Kühlein, Hilmar Nils
Tegeder, Irmgard
Möser, Christine
Lim, Hee-Young
Häussler, Annett
Spieth, Katharina
Jennes, Ingo
Marschalek, Rolf
Beckhaus, Tobias
Karas, Michael
Fauth, Markus
Ehnert, Corina
Geisslinger, Gerd
Niederberger, Ellen
author_sort Kühlein, Hilmar Nils
collection PubMed
description 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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spelling pubmed-30848082011-05-13 Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain Kühlein, Hilmar Nils Tegeder, Irmgard Möser, Christine Lim, Hee-Young Häussler, Annett Spieth, Katharina Jennes, Ingo Marschalek, Rolf Beckhaus, Tobias Karas, Michael Fauth, Markus Ehnert, Corina Geisslinger, Gerd Niederberger, Ellen PLoS One Research Article 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. Public Library of Science 2011-04-29 /pmc/articles/PMC3084808/ /pubmed/21572518 http://dx.doi.org/10.1371/journal.pone.0019270 Text en Kühlein et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Kühlein, Hilmar Nils
Tegeder, Irmgard
Möser, Christine
Lim, Hee-Young
Häussler, Annett
Spieth, Katharina
Jennes, Ingo
Marschalek, Rolf
Beckhaus, Tobias
Karas, Michael
Fauth, Markus
Ehnert, Corina
Geisslinger, Gerd
Niederberger, Ellen
Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
title Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
title_full Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
title_fullStr Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
title_full_unstemmed Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
title_short Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
title_sort nerve injury evoked loss of latexin expression in spinal cord neurons contributes to the development of neuropathic pain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084808/
https://www.ncbi.nlm.nih.gov/pubmed/21572518
http://dx.doi.org/10.1371/journal.pone.0019270
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