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MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice
The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). One-hundred-thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263360/ https://www.ncbi.nlm.nih.gov/pubmed/20657463 http://dx.doi.org/10.3390/molecules15053038 |
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author | Üçeyler, Nurcan Biko, Lydia Sommer, Claudia |
author_facet | Üçeyler, Nurcan Biko, Lydia Sommer, Claudia |
author_sort | Üçeyler, Nurcan |
collection | PubMed |
description | The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). One-hundred-thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL-28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain. |
format | Online Article Text |
id | pubmed-6263360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62633602019-01-02 MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice Üçeyler, Nurcan Biko, Lydia Sommer, Claudia Molecules Article The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). One-hundred-thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL-28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain. MDPI 2010-04-27 /pmc/articles/PMC6263360/ /pubmed/20657463 http://dx.doi.org/10.3390/molecules15053038 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Üçeyler, Nurcan Biko, Lydia Sommer, Claudia MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice |
title | MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice |
title_full | MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice |
title_fullStr | MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice |
title_full_unstemmed | MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice |
title_short | MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice |
title_sort | mdl-28170 has no analgesic effect on cci induced neuropathic pain in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263360/ https://www.ncbi.nlm.nih.gov/pubmed/20657463 http://dx.doi.org/10.3390/molecules15053038 |
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