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A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models

Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Wolter, Angelique;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Bucher, Christian H.;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Kurmies, Sebastian;
Affiliation
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Schreiner, Viktoria;
Affiliation
Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany
Konietschke, Frank;
Affiliation
Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany
Hohlbaum, Katharina;
Affiliation
Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany
Klopfleisch, Robert;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Löhning, Max;
Affiliation
Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany
Thöne-Reineke, Christa;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Buttgereit, Frank;
Affiliation
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Huwyler, Jörg;
Affiliation
Office for Animal Welfare and 3Rs, University of Zurich, Zurich, Switzerland
Jirkof, Paulin;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Rapp, Anna E.;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Lang, Annemarie

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as a potential future alternative to standard formulations available in Europe. Pharmacokinetics indicate a possible effectiveness for about 72 h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse fracture models (femoral osteotomy) and could, therefore, serve as a potent alternative to the application of Tramadol via the drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72 h, comparable to the effectiveness of Tramadol in the drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for rodents in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare.

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