Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model
Open Access
- 24 June 2021
- Vol. 13 (7), 1222
- https://doi.org/10.3390/v13071222
Abstract
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (BE 6335/2, BE 6335/4, CRC1292 project 02, CRC167 project B16 to AB)
- Charité 3R| Replace - Reduce – Refine (“Refinement of procedures causing severe suffering”, “Peter Hans Hofschneider Endowed Professorship”, “OXBERII_BIH1”)
This publication has 31 references indexed in Scilit:
- Update on MyocarditisJournal of Invasive Cardiology, 2012
- The viral genetic background determines the outcome of coxsackievirus B3 infection in outbred NMRI miceJournal of Medical Virology, 2007
- Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responsesPain, 2004
- Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adultsJournal of Invasive Cardiology, 2003
- TramadolDrugs, 2000
- Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.Journal of the American College of Cardiology, 1994
- The Pharmacology of TramadolDrugs, 1994
- Evidence for a noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic ratEuropean Journal of Pharmacology, 1992
- Cardiac Involvement in Postnatal RubellaActa Paediatrica, 1989
- MYOCARDITIS IN EXPERIMENTAL COXSACKIE B-3 INFECTIONCanadian Journal of Microbiology, 1959