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Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats
BACKGROUND: We have previously shown a sprouting of sympathetic fibers into the upper dermis of the skin following subcutaneous injection of complete Freund’s adjuvant (CFA) into the hindpaw. This sprouting correlated with an increase in pain-related sensitivity. We hypothesized that this sprouting...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737061/ https://www.ncbi.nlm.nih.gov/pubmed/23889761 http://dx.doi.org/10.1186/1744-8069-9-37 |
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author | Osikowicz, Maria Longo, Geraldine Allard, Simon Cuello, A Claudio Ribeiro-da-Silva, Alfredo |
author_facet | Osikowicz, Maria Longo, Geraldine Allard, Simon Cuello, A Claudio Ribeiro-da-Silva, Alfredo |
author_sort | Osikowicz, Maria |
collection | PubMed |
description | BACKGROUND: We have previously shown a sprouting of sympathetic fibers into the upper dermis of the skin following subcutaneous injection of complete Freund’s adjuvant (CFA) into the hindpaw. This sprouting correlated with an increase in pain-related sensitivity. We hypothesized that this sprouting and pain-related behavior were caused by an increase in nerve growth factor (NGF) levels. In this study, we investigated whether the inhibition of mature NGF degradation, using a matrix metalloproteinase 2 and 9 (MMP-2/9) inhibitor, was sufficient to reproduce a similar phenotype. RESULTS: Behavioral tests performed on male Sprague–Dawley rats at 1, 3, 7 and 14 days after intra-plantar MMP-2/9 inhibitor administration demonstrated that acute and chronic injections of the MMP-2/9 inhibitor induced sensitization, in a dose dependent manner, to mechanical, hot and cold stimuli as measured by von Frey filaments, Hargreaves and acetone tests, respectively. Moreover, the protein levels of mature NGF (mNGF) were increased, whereas the levels and enzymatic activity of matrix metalloproteinase 9 were reduced in the glabrous skin of the hind paw. MMP-2/9 inhibition also led to a robust sprouting of sympathetic fibers into the upper dermis but there were no changes in the density of peptidergic nociceptive afferents. CONCLUSIONS: These findings indicate that localized MMP-2/9 inhibition provokes a pattern of sensitization and fiber sprouting comparable to that previously obtained following CFA injection. Accordingly, the modulation of endogenous NGF levels should be considered as a potential therapeutic target for the management of inflammatory pain associated with arthritis. |
format | Online Article Text |
id | pubmed-3737061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37370612013-08-08 Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats Osikowicz, Maria Longo, Geraldine Allard, Simon Cuello, A Claudio Ribeiro-da-Silva, Alfredo Mol Pain Research BACKGROUND: We have previously shown a sprouting of sympathetic fibers into the upper dermis of the skin following subcutaneous injection of complete Freund’s adjuvant (CFA) into the hindpaw. This sprouting correlated with an increase in pain-related sensitivity. We hypothesized that this sprouting and pain-related behavior were caused by an increase in nerve growth factor (NGF) levels. In this study, we investigated whether the inhibition of mature NGF degradation, using a matrix metalloproteinase 2 and 9 (MMP-2/9) inhibitor, was sufficient to reproduce a similar phenotype. RESULTS: Behavioral tests performed on male Sprague–Dawley rats at 1, 3, 7 and 14 days after intra-plantar MMP-2/9 inhibitor administration demonstrated that acute and chronic injections of the MMP-2/9 inhibitor induced sensitization, in a dose dependent manner, to mechanical, hot and cold stimuli as measured by von Frey filaments, Hargreaves and acetone tests, respectively. Moreover, the protein levels of mature NGF (mNGF) were increased, whereas the levels and enzymatic activity of matrix metalloproteinase 9 were reduced in the glabrous skin of the hind paw. MMP-2/9 inhibition also led to a robust sprouting of sympathetic fibers into the upper dermis but there were no changes in the density of peptidergic nociceptive afferents. CONCLUSIONS: These findings indicate that localized MMP-2/9 inhibition provokes a pattern of sensitization and fiber sprouting comparable to that previously obtained following CFA injection. Accordingly, the modulation of endogenous NGF levels should be considered as a potential therapeutic target for the management of inflammatory pain associated with arthritis. BioMed Central 2013-07-29 /pmc/articles/PMC3737061/ /pubmed/23889761 http://dx.doi.org/10.1186/1744-8069-9-37 Text en Copyright © 2013 Osikowicz 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 Osikowicz, Maria Longo, Geraldine Allard, Simon Cuello, A Claudio Ribeiro-da-Silva, Alfredo Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats |
title | Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats |
title_full | Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats |
title_fullStr | Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats |
title_full_unstemmed | Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats |
title_short | Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats |
title_sort | inhibition of endogenous ngf degradation induces mechanical allodynia and thermal hyperalgesia in rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737061/ https://www.ncbi.nlm.nih.gov/pubmed/23889761 http://dx.doi.org/10.1186/1744-8069-9-37 |
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