Effect of prescribing and deprescribing oxycodone on pain and function in a mouse model of osteoarthritis: impact of polypharmacy and sex on response

Mach, J.; Blaker, C.; Winters, B.; Otsu, Y.; Clarke, E.; Allore, H.; Vander Wyk, B.; Winardi, K.; Peel, R.; Gregson, C.; Assareh, N.; Kourieh, M.; Hilmer, S. N.

doi:10.1101/2025.10.22.684045

bioRxiv · 10.1101/2025.10.22.684045

Effect of prescribing and deprescribing oxycodone on pain and function in a mouse model of osteoarthritis: impact of polypharmacy and sex on response

Mach, J.·Blaker, C.·Winters, B.·Otsu, Y.·Clarke, E.·Allore, H.·Vander Wyk, B.·Winardi, K.·Peel, R.·Gregson, C.·Assareh, N.·Kourieh, M.·Hilmer, S. N.

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Abstract

Osteoarthritis and polypharmacy are common in older adults. While not consistent with guidelines, opioid analgesia is commonly prescribed to older adults with osteoarthritis and other causes of chronic non-cancer pain. Long term use of opioids is associated with tolerance, addiction, loss of efficacy and adverse events. Thus, deprescribing (reducing or ceasing) opioids is often required. The effect of polypharmacy on the efficacy and safety of opioid prescribing and deprescribing in this setting is poorly understood. Here we aimed to assess the effects of chronic oxycodone, as monotherapy and in polypharmacy (oxycodone, citalopram, simvastatin, oxybutynin, and metoprolol), and of deprescribing oxycodone, on allodynia, physical and cognitive function, and daily activities in middle-aged, osteoarthritic male and female C57BL/6J mice (n=11-15/ group). Only oxycodone monotherapy reduced mechanical allodynia after 6 weeks of treatment. Chronic polypharmacy with oxycodone transiently increased mechanical allodynia in the injured limb and caused marked reductions in mobility, maximum walking speed, activities of daily living, and increased anxiety. Polypharmacy also altered daily activities detected by an automated animal behaviour recognition cage. Sex differences in treatment response were observed in frailty measurements and activity over 23 hours. Deprescribing oxycodone was well tolerated and did not alter physical or cognitive function but did reverse some of the daily activity changes and mechanical allodynia in polypharmacy treated animals only. This clinically relevant preclinical model provides an opportunity to understand the effects of prescribing and deprescribing opioids in older adults with osteoarthritis, including the impact of comedications and sex.

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Mach, J., Blaker, C., Winters, B., Otsu, Y., Clarke, E., Allore, H., Vander Wyk, B., Winardi, K., Peel, R., Gregson, C., Assareh, N., Kourieh, M., Hilmer, S. N.. 2025-10-23. Effect of prescribing and deprescribing oxycodone on pain and function in a mouse model of osteoarthritis: impact of polypharmacy and sex on response. https://doi.org/10.1101/2025.10.22.684045

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