Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model

Infection of mice with Coxsackievirus B3 (CVB3) triggers inflammation of the heart and this mouse model is commonly used to investigate underlying mechanisms and therapeutic aspects for viral myocarditis. Virus-triggered cytotoxicity and the activity of infiltrating immune cells contribute to cardia...

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Main Authors: Sandra Pinkert, Meike Kespohl, Nicolas Kelm, Ziya Kaya, Arnd Heuser, Karin Klingel, Antje Beling
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/7/1222
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author Sandra Pinkert
Meike Kespohl
Nicolas Kelm
Ziya Kaya
Arnd Heuser
Karin Klingel
Antje Beling
author_facet Sandra Pinkert
Meike Kespohl
Nicolas Kelm
Ziya Kaya
Arnd Heuser
Karin Klingel
Antje Beling
author_sort Sandra Pinkert
collection DOAJ
description Infection of mice with Coxsackievirus B3 (CVB3) triggers inflammation of the heart and this mouse model is commonly used to investigate underlying mechanisms and therapeutic aspects for viral myocarditis. Virus-triggered cytotoxicity and the activity of infiltrating immune cells contribute to cardiac tissue injury. In addition to cardiac manifestation, CVB3 causes cell death and inflammation in the pancreas. The resulting pancreatitis represents a severe burden and under such experimental conditions, analgesics may be supportive to improve the animals’ well-being. Notably, several known mechanisms exist by which analgesics can interfere with the immune system and thereby compromise the feasibility of the model. We set up a study aiming to improve animal welfare while ensuring model integrity and investigated how tramadol, an opioid, affects virus-induced pathogenicity and immune response in the heart. Tramadol was administered seven days prior to a CVB3 infection in C57BL/6 mice and treatment was continued until the day of analysis. Tramadol had no effect on the virus titer or viral pathogenicity in the heart tissue and the inflammatory response, a hallmark of myocardial injury, was maintained. Our results show that tramadol exerts no disruptive effects on the CVB3 myocarditis mouse model and, therefore, the demonstrated protocol should be considered as a general analgesic strategy for CVB3 infection.
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spelling doaj.art-4adc994e783c4863956e41ca6b0bc33d2023-11-22T01:33:54ZengMDPI AGViruses1999-49152021-06-01137122210.3390/v13071222Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse ModelSandra Pinkert0Meike Kespohl1Nicolas Kelm2Ziya Kaya3Arnd Heuser4Karin Klingel5Antje Beling6Institute of Biochemistry, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyInstitute of Biochemistry, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyInstitute of Biochemistry, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyKardiologie, Angiologie und Pneumologie, Medizinische Klinik für Innere Medizin III, Universitätsklinikum Heidelberg, 69120 Heidelberg, GermanyAnimal Phenotyping Platform, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, GermanyCardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, 72076 Tuebingen, GermanyInstitute of Biochemistry, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, GermanyInfection of mice with Coxsackievirus B3 (CVB3) triggers inflammation of the heart and this mouse model is commonly used to investigate underlying mechanisms and therapeutic aspects for viral myocarditis. Virus-triggered cytotoxicity and the activity of infiltrating immune cells contribute to cardiac tissue injury. In addition to cardiac manifestation, CVB3 causes cell death and inflammation in the pancreas. The resulting pancreatitis represents a severe burden and under such experimental conditions, analgesics may be supportive to improve the animals’ well-being. Notably, several known mechanisms exist by which analgesics can interfere with the immune system and thereby compromise the feasibility of the model. We set up a study aiming to improve animal welfare while ensuring model integrity and investigated how tramadol, an opioid, affects virus-induced pathogenicity and immune response in the heart. Tramadol was administered seven days prior to a CVB3 infection in C57BL/6 mice and treatment was continued until the day of analysis. Tramadol had no effect on the virus titer or viral pathogenicity in the heart tissue and the inflammatory response, a hallmark of myocardial injury, was maintained. Our results show that tramadol exerts no disruptive effects on the CVB3 myocarditis mouse model and, therefore, the demonstrated protocol should be considered as a general analgesic strategy for CVB3 infection.https://www.mdpi.com/1999-4915/13/7/1222infectionmyocarditispancreatitisrefinementanalgesia
spellingShingle Sandra Pinkert
Meike Kespohl
Nicolas Kelm
Ziya Kaya
Arnd Heuser
Karin Klingel
Antje Beling
Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
Viruses
infection
myocarditis
pancreatitis
refinement
analgesia
title Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
title_full Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
title_fullStr Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
title_full_unstemmed Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
title_short Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
title_sort exploration of analgesia with tramadol in the coxsackievirus b3 myocarditis mouse model
topic infection
myocarditis
pancreatitis
refinement
analgesia
url https://www.mdpi.com/1999-4915/13/7/1222
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