Publikationsdatenbank

Pain assessment and management in mouse femoral fracture models (2024)

Art

Hochschulschrift

Autor

Wolter, Angélique (WE 11)

Quelle

Berlin: Mensch und Buch Verlag, 2024 — IV, 126 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/44189

Kontakt

Institut für Tierschutz, Tierverhalten und Versuchstierkunde

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

Abstract / Zusammenfassung

Preclinical research using animal models is still imperative in biomedical sciences to address the unmet clinical needs in many areas such as fracture healing disorders. General ethical and legal requirements must be carefully considered to provide scientific quality and integrity in animal-based studies. Sufficient reporting, adequate pain assessment and adapted pain management in animal-based research are crucial to generate reliable, reproducible, and comparable data, in line with the humane use of animals in research. However, ongoing discussions in the scientific community and various systematic literature analyses have indicated that the overall reporting quality in many areas of animal-based biomedical research is still inadequate. Therefore, the first aim of this thesis was to evaluate the status quo of the reporting accuracy of different general and model-specific Parameters and the respective analgesia regimes in studies using adequately stabilized mouse femoral fracture models. High reporting accuracies were identified for the used fixation methods and fracturing procedures as well as the used strain, age, and sex of the mice, while insufficient reporting was found regarding the substrain and genetic background of the mice, body weight, hygiene monitoring, anesthesia, and analgesia. The systematic review also showed marked differences in the route, timepoint and duration of application as well as analgesic dosages, further indicating a need for more evidence-based data on model-adapted pain Management protocols. The adequate pain assessment and an adapted stress-reduced pain management in laboratory rodents are ongoing challenges, yet essential to improve animal welfare and increase scientific validity and reproducibility. To reduce handling-associated stress while covering the period of greatest pain, the application of analgesics via the drinking water or the injection of sustained-release preparations can be used as an addition or an alternative to repeated injections. However, no sustained-release preparation for pain management in mice is currently available on the European market. The introduction of such a sustained-release buprenorphine would, therefore, be of great benefit for extended pain relief in a variety of different mouse models. Thus, the second part of the thesis focused on the evaluation of the analgesic efficacy of a newly developed depot formulation of buprenorphine (BUP-Depot) for prolonged post-operative pain relief in two mouse osteotomy models. Following a single injection, the analyses of various general and model-specific parameters yielded promising pain-relieving properties of the BUP-Depot for up to 72h post-surgical in female and male mice in both models. The availability of such a sustained-release formulation of buprenorphine would greatly help to further broaden the field of analgesic options in Europe and could have the potential to further refine analgesia in animal-based studies in Europe. In the third part of the thesis, rearing behavior was evaluated to serve as an additional and meaningful model-specific indicator for pain in the first 72h after femoral osteotomy in mice. The analyzed data indicated significantly reduced rearing behavior after osteotomy, independent of sex or fixation, while anesthesia and analgesia alone did not impact rearing behavior. However, there was no clear evidence that the analysis of rearing behavior could serve as a meaningful sole indicator for residual model-specific skeletal pain in the analyzed models. Thus, further studies are needed to evaluate the value and predictive capacity of rearing behavior to assess pain in skeletal-impaired mouse models. Overall, this thesis demonstrates that the accuracy of reporting in mouse fracture models needs to be further improved and that guidelines such as the ARRIVE guidelines should be more actively addressed in future studies. Furthermore, the data demonstrated safe use and efficient analgesia of a newly developed sustained-release buprenorphine for 72h after femoral osteotomy and underline the need and relevance of the availability of sustained-release analgesics for refined analgesia in laboratory mice in Europe. Lastly, this thesis indicates an ongoing need for further in-depth analysis and evaluation of easy-to-use and reliable indicators for pain in laboratory mice to ensure animal welfare.