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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...

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Autores principales: Üçeyler, Nurcan, Biko, Lydia, Sommer, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2010
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.
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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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