Cargando…
Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain
BACKGROUND: Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649910/ https://www.ncbi.nlm.nih.gov/pubmed/19228393 http://dx.doi.org/10.1186/1744-8069-5-7 |
_version_ | 1782165072019193856 |
---|---|
author | Persson, Anna-Karin Gebauer, Mathias Jordan, Suzana Metz-Weidmann, Christiane Schulte, Anke M Schneider, Hans-Christoph Ding-Pfennigdorff, Danping Thun, Jonas Xu, Xiao-Jun Wiesenfeld-Hallin, Zsuzsanna Darvasi, Ariel Fried, Kaj Devor, Marshall |
author_facet | Persson, Anna-Karin Gebauer, Mathias Jordan, Suzana Metz-Weidmann, Christiane Schulte, Anke M Schneider, Hans-Christoph Ding-Pfennigdorff, Danping Thun, Jonas Xu, Xiao-Jun Wiesenfeld-Hallin, Zsuzsanna Darvasi, Ariel Fried, Kaj Devor, Marshall |
author_sort | Persson, Anna-Karin |
collection | PubMed |
description | BACKGROUND: Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG) following axotomy. But which contribute to pain phenotype versus other nerve injury-evoked processes such as nerve regeneration? Using the L5 spinal nerve ligation model of neuropathy we examined differential changes in gene expression in the L5 (and L4) DRGs in five mouse strains with contrasting susceptibility to neuropathic pain. We sought genes for which the degree of regulation correlates with strain-specific pain phenotype. RESULTS: In an initial experiment six candidate genes previously identified as important in pain physiology were selected for in situ hybridization to DRG sections. Among these, regulation of the Na(+ )channel α subunit Scn11a correlated with levels of spontaneous pain behavior, and regulation of the cool receptor Trpm8 correlated with heat hypersensibility. In a larger scale experiment, mRNA extracted from individual mouse DRGs was processed on Affymetrix whole-genome expression microarrays. Overall, 2552 ± 477 transcripts were significantly regulated in the axotomized L5DRG 3 days postoperatively. However, in only a small fraction of these was the degree of regulation correlated with pain behavior across strains. Very few genes in the "uninjured" L4DRG showed altered expression (24 ± 28). CONCLUSION: Correlational analysis based on in situ hybridization provided evidence that differential regulation of Scn11a and Trpm8 contributes to across-strain variability in pain phenotype. This does not, of course, constitute evidence that the others are unrelated to pain. Correlational analysis based on microarray data yielded a larger "look-up table" of genes whose regulation likely contributes to pain variability. While this list is enriched in genes of potential importance for pain physiology, and is relatively free of the bias inherent in the candidate gene approach, additional steps are required to clarify which transcripts on the list are in fact of functional importance. |
format | Text |
id | pubmed-2649910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26499102009-03-03 Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain Persson, Anna-Karin Gebauer, Mathias Jordan, Suzana Metz-Weidmann, Christiane Schulte, Anke M Schneider, Hans-Christoph Ding-Pfennigdorff, Danping Thun, Jonas Xu, Xiao-Jun Wiesenfeld-Hallin, Zsuzsanna Darvasi, Ariel Fried, Kaj Devor, Marshall Mol Pain Research BACKGROUND: Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG) following axotomy. But which contribute to pain phenotype versus other nerve injury-evoked processes such as nerve regeneration? Using the L5 spinal nerve ligation model of neuropathy we examined differential changes in gene expression in the L5 (and L4) DRGs in five mouse strains with contrasting susceptibility to neuropathic pain. We sought genes for which the degree of regulation correlates with strain-specific pain phenotype. RESULTS: In an initial experiment six candidate genes previously identified as important in pain physiology were selected for in situ hybridization to DRG sections. Among these, regulation of the Na(+ )channel α subunit Scn11a correlated with levels of spontaneous pain behavior, and regulation of the cool receptor Trpm8 correlated with heat hypersensibility. In a larger scale experiment, mRNA extracted from individual mouse DRGs was processed on Affymetrix whole-genome expression microarrays. Overall, 2552 ± 477 transcripts were significantly regulated in the axotomized L5DRG 3 days postoperatively. However, in only a small fraction of these was the degree of regulation correlated with pain behavior across strains. Very few genes in the "uninjured" L4DRG showed altered expression (24 ± 28). CONCLUSION: Correlational analysis based on in situ hybridization provided evidence that differential regulation of Scn11a and Trpm8 contributes to across-strain variability in pain phenotype. This does not, of course, constitute evidence that the others are unrelated to pain. Correlational analysis based on microarray data yielded a larger "look-up table" of genes whose regulation likely contributes to pain variability. While this list is enriched in genes of potential importance for pain physiology, and is relatively free of the bias inherent in the candidate gene approach, additional steps are required to clarify which transcripts on the list are in fact of functional importance. BioMed Central 2009-02-19 /pmc/articles/PMC2649910/ /pubmed/19228393 http://dx.doi.org/10.1186/1744-8069-5-7 Text en Copyright © 2009 Persson et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Persson, Anna-Karin Gebauer, Mathias Jordan, Suzana Metz-Weidmann, Christiane Schulte, Anke M Schneider, Hans-Christoph Ding-Pfennigdorff, Danping Thun, Jonas Xu, Xiao-Jun Wiesenfeld-Hallin, Zsuzsanna Darvasi, Ariel Fried, Kaj Devor, Marshall Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
title | Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
title_full | Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
title_fullStr | Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
title_full_unstemmed | Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
title_short | Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
title_sort | correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649910/ https://www.ncbi.nlm.nih.gov/pubmed/19228393 http://dx.doi.org/10.1186/1744-8069-5-7 |
work_keys_str_mv | AT perssonannakarin correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT gebauermathias correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT jordansuzana correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT metzweidmannchristiane correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT schulteankem correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT schneiderhanschristoph correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT dingpfennigdorffdanping correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT thunjonas correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT xuxiaojun correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT wiesenfeldhallinzsuzsanna correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT darvasiariel correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT friedkaj correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain AT devormarshall correlationalanalysisforidentifyinggeneswhoseregulationcontributestochronicneuropathicpain |