• Luke A Pattison, Alexander Cloake, Sampurna Chakrabarti, Helen Hilton, Rebecca H Rickman, James P Higham, Michelle Y Meng, Luke W Paine, Maya Dannawi, Lanhui Qiu, Anne Ritoux, David C Bulmer, Gerard Callejo, and SmithEwan St JohnESJ0000-0002-2699-1979.
• Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom. Dr. Chakrabarti is now with Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. Dr. Callejo is now with Department of Biomedicine, Medical School, Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain.
• Pain. 2024 Mar 5.

AbstractThe pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical 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 that 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 patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing 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 naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, 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.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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