Identifying more clinically effective analgesic regimens and potential strain differences in pain perception in mice using a novel Operant Pain Assay

This project has two inter-linked objectives: [1] to establish more effective analgesic regimens for laboratory mice and [2] to establish whether pain perception differs between mouse strains. We estimate that annually ~13% (~400k in the UK, >4 million worldwide) of mice used in regulated research undergo potentially painful procedures. Critically, we cannot currently manage post-procedural pain effectively in mice, making this a significant focus for 3Rs research. Unalleviated and uncontrolled pain is a considerable welfare and scientific concern affecting a range of disciplines. Effective pain management is therefore integral to the 3Rs that underpin in vivo research. We will first rapidly screen routinely used (meloxicam, morphine), novel (Tapentadol) and multi-modal (combinations of the above) analgesic regimens to assess their efficacy in three common strains of laboratory mice (C57Bl/6, CD1 and C3He) using the Orofacial Operant Pain Assay. This novel automated nociceptive test is considered more clinically relevant for developing analgesia. We will then establish which of these regimens demonstrate efficacy following routine surgery (vasectomy) in these strains using established and validated behavioural indices (behaviour, facial expressions, burrowing, nest building).

As the Orofacial Operant Pain Assay uses an operant-conflict paradigm requiring higher cognitive processing, it can be used to determine whether pain perception differs between these mouse strains when exposed to a standard nociceptive stimulus. This data will be compared to that of the post-surgical study to determine whether any strain differences observed in the behavioural indices relate to differences in pain perception. Establishing whether common strains differ in their analgesic requirements and potentially their pain perception is critical for effective pain management and to comply with the 3Rs, improve welfare and enhance scientific outcomes.