Publikationsdatenbank

Evaluating the pain management in a mouse osteotomy model:
integrating a refinement approach in a basic research study (2019)

Art

Hochschulschrift

Autor

Durst, Mattea Sophie (WE 11)

Quelle

Berlin: Mensch und Buch Verlag Berlin, 2019 — xi, 97 Seiten

ISBN: 978-3-86387-983-9

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/25235

Kontakt

Institut für Tierschutz, Tierverhalten und Versuchstierkunde

Königsweg 67
14163 Berlin
+49 30 838 61146
tierschutz@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Tramadol applied via the drinking water is a commonly used analgesia in the mouse osteotomy model. Another opioid that can be used is buprenorphine. The recommendation for tramadol in the drinking water was increased 40-fold by the GV-SOLAS from 2010 to 2015. A recommendation on buprenorphine is given for injection but not for the application in the drinking water. Nevertheless, some standard operating procedures are found on buprenorphine applied via the drinking water. Model-specific recommendations on pain management in the mouse osteotomy model are not available. In the current study, three pain management protocols, two dosages of tramadol and buprenorphine applied via the drinking water in the mouse osteotomy model were tested. This refinement project was integrated into a basic research study. The aim of this project was to provide researchers with a specific recommendation on pain treatment in bone-linked mouse models. The three pain management protocols (tramadol 0.1 mg/ml, tramadol 1 mg/ml and buprenorphine 0.009 mg/ml in the drinking water) were evaluated for feasibility, analgesic efficacy and impact on the bone healing in the mouse osteotomy model. The feasibility was tested with the assessment of body weight, food and water intake, serum level of tramadol and M1 as well as stress measurements. The stress measurements consisted of the analysis of fecal corticosterone metabolites as a parameter for short-term stress and the histological assessment of adrenal glands as a measurement for long-term stress. To check for possible side effects of the different medications, the livers were histologically assessed. With the help of parameters such as a clinical score, nest complexity, explorative behavior and an activity assessment the animals were screened for behavior indicating pain or reduced wellbeing. Model-specific pain parameters like the limp score, dragging score, flinching, guarding, grooming time of the operated limb and rear up time were applied. These behavioral and model-specific tests are used to evaluate the analgesic efficiency of tramadol and buprenorphine. To grade the impact of the different pain management protocols on the animal model parameters of bone healing were assessed. These included in vitro μCT and histology of the osteotomized bone after euthanasia. During the refinement project, more questions came up regarding the pre-emptive injection of buprenorphine. Therefore, a study on the impact of pre-emptive injected buprenorphine on bleeding during the surgery was conducted. The animals used in the study drank after the procedure with more drinking events in the night compared to the day. A reduced wellbeing in animals treated with the tramadol dosage of 1 mg/ml was found. Also seen in the body weight loss, reduced food intake and drinking events, the clinical scoring and nest complexity. Short stress was visible on day one in all animals, but there were no signs of histological changes in the adrenal glands. The used clinical scoring was not specific to pain, but rather displayed a reduced wellbeing in Thigh animals. In the explorative behavior Tlow animals showed the fastest recovery. Operated animals had lowest activity with no clear differences between the treatment groups. The pain-specific parameters showed no better pain relief in the high tramadol group. No impact of the changed pain management protocol on the bone healing and therefore on the main read-out of the mouse osteotomy model was seen. One animal was euthanized prior to the end of the study which was not related to the analgesic treatment but rather due to a preexisting potential metabolic disorder. Tramadol of the low dosage showed serum concentrations that can be assumed sufficient to relief pain compared to human values. The time point of pre-emptive buprenorphine injection influenced the bleeding during surgery, specifically an injection 1h before the surgery increased bleeding. Additionally, buprenorphine may alter wound healing. After successfully conducting this integrated refinement study, more projects of this kind can be recommended to gain knowledge of possible refinement benefits in specific animal models. Tramadol and buprenorphine in the drinking water is an efficient route of applying analgesia in the MOMo. The concern of a reduced water intake was not confirmed in tramadol of the low dosage and in buprenorphine. The use of tramadol in the dosage of 1 mg/ml is not necessary in the MOMo. It offers no extra benefit in pain reduction but rather reduces wellbeing in the animals. Tramadol in the dosage of 0.1 mg/ml or buprenorphine in the drinking water are a sufficient method to relief pain in the MOMo.