Abstract
Ethical responsibility, legal requirements and the need to improve the quality of research create a growing interest in the welfare of laboratory animals. Judging the welfare of animals requires readout parameters, which are valid and sensitive as well as specific to assess distress after different interventions. In the present study, we evaluated the sensitivity and specificity of different non-invasive parameters (body weight change, faecal corticosterone metabolites concentration, burrowing and nesting activity) by receiver operating characteristic curves and judged the merit of a multi-parametric analysis by logistic regression. Chronic pancreatitis as well as laparotomy caused significant changes in all parameters. However, the accuracy of these parameters was different between the two animal models. In both animal models, the multi-parametric analysis relying on all the readout parameters had the highest accuracy when predicting distress. This multi-parametric analysis revealed that C57BL/6 mice during the course of chronic pancreatitis often experienced less distress than mice after laparotomy. Interestingly these data also suggest that distress does not steadily increase during chronic pancreatitis. In conclusion, combining these non-invasive methods for severity assessment represents a reliable approach to evaluate animal distress in models such as chronic pancreatitis.
Highlights
Laboratory animals represent a valuable tool for mimicking physiological conditions in humans and are, still widely used for biomedical research in the pursuit of understanding the pathophysiology of a disease and exploring novel treatments[1,2]
This study demonstrates that all distress readout parameters (FCM, body weight change and burrowing as well as nesting activity) are significantly changed by both chronic pancreatitis (CP) and laparotomy
This suggests their broad applicability to assess distress after completely distinct interventions. The accuracy of these parameters when distinguishing between healthy mice and mice after an intervention was different between CP and laparotomy
Summary
Laboratory animals represent a valuable tool for mimicking physiological conditions in humans and are, still widely used for biomedical research in the pursuit of understanding the pathophysiology of a disease and exploring novel treatments[1,2]. The 3Rs (replacement, reduction and refinement of animal experiments) have been coined by Russell and Burch[3] more than 50 years ago and are the basis of national and international regulations of animal experiments In accordance with this concept, the European Union Directive 2010/63/EU and many local institutional animal care and use committees in the USA demand to provide adequate information to assess the potential distress and pain that animals might experience during an experiment[4,5]. CP can lead to endocrine and exocrine pancreatic insufficiency with severe complications[29] These facts altogether create a crucial need for extensive scientific research in the field of CP in order to explore pathophysiological mechanisms and novel therapeutic approaches. While some animal models for CP do not reproduce all histopathological features of this disease and some animal models have a relatively high mortality rate, repetitive i.p cerulein injections very reliably cause CP30,31
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