{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:39Z","timestamp":1787030019933,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BE 6335\/2, BE 6335\/4, CRC1292 project 02, CRC167 project B16 to AB"],"award-info":[{"award-number":["BE 6335\/2, BE 6335\/4, CRC1292 project 02, CRC167 project B16 to AB"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charit\u00e9 3R| Replace - Reduce \u2013 Refine","award":["\u201cRefinement of procedures causing severe suffering\u201d"],"award-info":[{"award-number":["\u201cRefinement of procedures causing severe suffering\u201d"]}]},{"name":"Foundation for Experimental Biomedicine Zurich, Switzerland","award":["\u201cPeter Hans Hofschneider Endowed Professorship\u201d"],"award-info":[{"award-number":["\u201cPeter Hans Hofschneider Endowed Professorship\u201d"]}]},{"name":"OX\/BER-BIH Joint Seed Funding Fund","award":["\u201cOXBERII_BIH1\u201d"],"award-info":[{"award-number":["\u201cOXBERII_BIH1\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2019 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.<\/jats:p>","DOI":"10.3390\/v13071222","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T23:22:14Z","timestamp":1624576934000},"page":"1222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Sandra","family":"Pinkert","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung (DZHK), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5897-8747","authenticated-orcid":false,"given":"Meike","family":"Kespohl","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Kelm","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9 (BIH), 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-0836","authenticated-orcid":false,"given":"Ziya","family":"Kaya","sequence":"additional","affiliation":[{"name":"Kardiologie, Angiologie und Pneumologie, Medizinische Klinik f\u00fcr Innere Medizin III, Universit\u00e4tsklinikum Heidelberg, 69120 Heidelberg, Germany"},{"name":"Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung (DZHK), Partner Site Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Heuser","sequence":"additional","affiliation":[{"name":"Animal Phenotyping Platform, Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-2498","authenticated-orcid":false,"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[{"name":"Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-5248","authenticated-orcid":false,"given":"Antje","family":"Beling","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung (DZHK), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.jacc.2011.09.074","article-title":"Update on Myocarditis","volume":"59","author":"Kindermann","year":"2012","journal-title":"J. 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