Abstract
Chemotherapy-induced mucositis is an extremely painful condition that occurs in 40–60% of patients undergoing chemotherapy. As mucositis currently has no effective treatment, and due to the self-limiting nature of the condition, the major treatment aims are to manage symptoms and limit pain with significance placed on improving patient quality of life. Rodent models are frequently used in mucositis research. These investigations typically assess pathological outcomes, yet fail to include a measure of affective state; the key therapeutic goal. Assessment of cognitive biases is a novel approach to determining the affective state of animals. Consequently, this study aimed to validate a cognitive bias test through a judgement bias paradigm to measure affective state in a rat model of chemotherapy-induced intestinal mucositis. Rats with intestinal mucositis demonstrated a negative affective state, which was partially ameliorated by analgesic administration, whilst healthy rats showed an optimistic response. This study concluded that the judgement bias test was able to evaluate the emotional state of rats with chemotherapy-induced mucositis. These findings provide a foundation for future refinement to the experimental design associated with the animal model that will expedite successful transitioning of novel therapeutics to clinical practice, and also improve humane endpoint implementation.
Highlights
Improving patient quality of life and the impact on affective state[8,10]
Despite the self-limiting nature of the condition and the negative impact on patient quality of life, cognitive parameters such as affective state are rarely studied in animal models
This study represents the first to have demonstrated and validated a reliable judgement bias test to assess affective state exhibited by rats with chemotherapy-induced mucositis
Summary
Improving patient quality of life and the impact on affective state[8,10]. Affective state being a subjective feeling state that encompasses different mood states, such as anxiety, depression, joy or happiness[11]. The majority of preclinical studies in mucositis have used rodents to investigate pathogenesis of the condition and effectiveness of novel therapeutics These investigations typically assess pathological outcomes such as gut histological architecture or inflammatory response, yet fail to include a measure of affective state; the key therapeutic goal. These behavioural and physiological measures provide important information on the arousal of an emotion, they are simplistic and do not provide a complex interpretation of the positive and negative valence of an emotion[12,13,14,15] One such method that has been derived from the human psychology field, and has been used as an indicator of affective state, is assessment of cognitive biases[16]. Further validation of the test was performed through the addition of an opioid palliative treatment, buprenorphine, which was expected to improve wellbeing
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