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Sci Rep. 2019 Jul 24;9(1):10749. doi: 10.1038/s41598-019-47186-5.

Administration of Tramadol or Buprenorphine via the drinking water for post-operative analgesia in a mouse-osteotomy model.

Author information

1
Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
2
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Berlin, Germany.
3
Institute of Veterinary Pathology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
4
Unit of Physiology, Pathophysiology and Experimental Endocrinology, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
5
Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
6
German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Berlin, Germany.
7
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Julius Wolff Institute and Center for Musculoskeletal Surgery, Berlin, Germany.
8
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin Brandenburg Center for Regenerative Therapies, Berlin, Germany.
9
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Berlin, Germany. annemarie.lang@charite.de.
10
German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Berlin, Germany. annemarie.lang@charite.de.
11
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin Brandenburg Center for Regenerative Therapies, Berlin, Germany. annemarie.lang@charite.de.

Abstract

Adequate analgesia is essential whenever pain might occur in animal experiments. Unfortunately, the selection of suitable analgesics for mice in bone-linked models is limited. Here, we evaluated two analgesics - Tramadol [0.1 mg/ml (Tlow) vs. 1 mg/ml (Thigh)] and Buprenorphine (Bup; 0.009 mg/ml) - after a pre-surgical injection of Buprenorphine, in a mouse-osteotomy model. The aim of this study was to verify the efficacy of these opioids in alleviating pain-related behaviors, to provide evidence for adequate dosages and to examine potential side effects. High concentrations of Tramadol affected water intake, drinking frequency, food intake and body weight negatively in the first 2-3 days post-osteotomy, while home cage activity was comparable between all groups. General wellbeing parameters were strongly influenced by anesthesia and analgesics. Model-specific pain parameters did not indicate more effective pain relief at high concentrations of Tramadol. In addition, ex vivo high-resolution micro computed tomography (µCT) analysis and histology analyzing bone healing outcomes showed no differences between analgesic groups with respect to newly formed mineralized bone, cartilage and vessels. Our results show that high concentrations of Tramadol do not improve pain relief compared to low dosage Tramadol and Buprenorphine, but rather negatively affect animal wellbeing.

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