Abstract
Behavioural indicators of affective state, including burrowing, clinical scores and the Mouse Grimace Score have not yet been validated in mouse models of chronic gastrointestinal disease. Additionally, a comparison of these methods has not been characterised. This study aimed to determine which behavioural assessment was the optimal indicator of disease, evidenced by correlation with clinically-assessed measures, in an azoxymethane (AOM)/dextran sulphate sodium (DSS) mouse model of colitis-associated colorectal cancer. C57BL/6 mice were allocated to four groups (n = 10/group); 1) saline control, 2) saline+buprenorphine, 3) AOM+DSS+water, 4) AOM+DSS+buprenorphine. Mice were gavaged thrice weekly with water or buprenorphine (0.5mg/kg; 80μL) for 9 weeks. Disease activity index (DAI) was measured daily; burrowing and grimace analyses occurred on days -1, 5, 19, 26, 40, 47 and 61. Colonoscopies were performed on days 20, 41 and 62. All animals were euthanized on day 63. Burrowing activity and retrospective grimace analyses were unaffected (P>0.05), whilst DAI was significantly increased (P<0.05) in mice with colitis-associated colorectal cancer compared to normal controls. In addition, DAI was positively correlated with colonoscopically-assessed severity and tumour number (P<0.05). We conclude that traditional measures of DAI or clinical scoring provide the most reliable assessment of wellbeing in mice with colitis-associated colorectal cancer.
Highlights
Pain, as defined by the Oxford dictionary, refers to a ‘highly unpleasant physical sensation caused by illness or injury’
Mice administered buprenorphine and treated with AOM/dextran sulphate sodium (DSS) presented with increased colitis severity on day 20 and decreased colitis severity scores on day 62 compared to AOM/DSS controls (P
The Mouse Grimace Scale’ (MGS) scores obtained through real-time and retrospective analyses were unable to be validated in regards to pain alleviation in this chronic study, we were able to conclude that real-time grimace scores and daily clinical scores were correlated with increased colitis severity and tumour number across treatment groups
Summary
As defined by the Oxford dictionary, refers to a ‘highly unpleasant physical sensation caused by illness or injury’. Rodents are the most widely used species and it is estimated that globally approximately 4.6 million will experience procedure-related pain [1]. Prevention and alleviation of pain through accurate pain assessment and appropriate analgesic use should be a priority for researchers working with laboratory animals [2]. Assessment of pain is challenging in all animal species, and is problematic in rodent-prey species that mask pain as part of a survival mechanism [3].
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