benjamin-chan / bdp2-448-lovasz

Objective

Studies have shown that “bystander” mice housed and tested in the same room as mice subjected to inflammatory pain or withdrawal from morphine or alcohol develop corresponding hyperalgesia^6^. We have compelling preliminary data that suggest mice also experience sympathetic or “empathetic” sickness responses when housed near sick animals, in that control mice housed near mice experiencing cancer cachexia also consume less food. This may have serious implications within the laboratory animal medicine community. First, this raises animal welfare concerns, as these mice appear to be experiencing cachexia as well. Second, when the empathetic animals consume less food in parallel to the sick animals’ decreased food intake, a larger sample size is needed to detect a statistically significant difference between groups. In short, more animals are needed for a study. The first aim of our study is to determine whether exposure to soiled bedding from ill mice will result in sickness behavior. Studies of “sympathetic” pain in mice^6^ have suggested an olfactory cause, so our second aim is to determine whether olfactory cues result in cachexia in control mice housed next to mice ill from cancer. Our third aim is to determine whether the cachexia experienced by control animals is a result of stress. The results of these studies could have significant impacts on animal welfare, reduction in animal numbers, and recommendations on housing animals.

Study design is a crossover trial. All study mice are healthy, non-diseased mice. Mice are exposed to bedding soiled by sick mice and bedding soiled by non-sick mice. Mice are randomized to the order in which they are exposed, A-B or B-A. So each mouse is exposed to both bedding types, and serve as their own control.

The primary outcome is pre-post change in feed consumption (difference in the weight of food consumed at t = 0 and t = ??). Feed consumption is standardized/normalized by body weight, also measured at the same time points. Feed weight and body weight are measured at 0, 2, 4, 12, 24, 36, 48 hours after exposure to each bedding type. The post time point has yet to be determined. The planned model is a linear model to estimate the magnitude of the bedding effect on the pre-post change in feed consumption. The model can accommodate mouse-level covariates.

A possible secondary analysis will be to model the longitudinal profile of feed consumption from 0 to 48 hours. This analysis will not be a part of this project agreement, but may be added later as an amendment.

The deliverables assume the investigator will provide a data file requiring minimal data cleaning.

Deliverables

• Linear model for the primary outcome estimating the magnitude of the bedding effect on pre-post change in feed consumption.

• Text, tables, and figures describing methods and results suitable for a manuscript