Digging deeper into pain – an ethological behavior assay correlating well-being in mice with human pain experience

Abstract

The pressing need for safer, more efficacious analgesics is felt worldwide. Pre-clinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays which measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human chronic pain patients who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their on-going level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naïve mice of both sexes. By contrast, deficits in digging were seen following acute knee inflammation. In the monosodium iodoacetate knee osteoarthritis model, the decrease in digging observed was not fully ameliorated by a clinically used drug, gabapentin, which reflected the opinion of human patients regarding its effectiveness. Lastly, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals.

Intestinal barrier function in the naked mole-rat: an emergent model for gastrointestinal insights

“…Digestive pathologies stand out as the most common type of disease worldwide ( 1 ). Importantly, they result in a significant reduction in the quality of life for patients and represent a multi-billion healthcare burden globally ( 2–5 ). Intestinal barrier dysfunction is a common feature of most gastrointestinal diseases, including coeliac disease, inflammatory bowel disease, metabolic dysfunction-associated liver disease and disorders of gut-brain interaction ( 6 ).…”