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Updated: Feb 9, 2026

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Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study
Xiaobu Ye1, MariaLisa Itzoe1, Rachel Sarabia-Estrada1
1Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Abstract:
Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg) showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.
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