Morphine‐Induced Analgesia in the Hot‐Plate Test: Comparison between NMRInu/nu and NMRI mice

Abstract: NMRI nu/nu mice are frequently used in cancer research, but their use in behavioural pain tests is unexplored. As behaviour of NMRI mice in pain tests is well‐documented, a hot‐plate test was performed comparing acute thermal nociception in NMRI nu/nu and NMRI mice – untreated and morphine‐treated – to estimate the usefulness of NMRI nu/nu mice for further research on cancer pain. In both strains, morphine dose‐dependently increased response latencies, number of animals reaching cut‐off times and AUC values. Yet in NMRI nu/nu mice, as compared to NMRI mice, all curves were shifted to the right. In order to be comparable, cut‐off times must express a similar degree of baseline response augmentations. NMRI nu/nu mice had substantially lower pre‐drug latencies, indicating a lowered threshold for painful thermal stimuli, therefore effects of morphine in NMRI nu/nu mice were also analysed using a lower cut‐off time. Doing so, morphine resulted in similar effects in both strains. The effects were independent of hot‐plate temperature, because similar results were obtained using temperatures of 50 and 55 °. The different morphine sensitivity of NMRI nu/nu compared to NMRI mice primarily seems to depend upon differences in thermal threshold, probably induced by the different genotype of both strains. To determine whether cancer alters pain threshold or morphine analgesia, LoVo tumour‐bearing NMRI nu/nu mice were also tested. The tumour presence had no influence on withdrawal latencies or morphine efficacy. In general it can be concluded that NMRI nu/nu mice with or without tumour can be used for nociceptive testing if baseline sensitivity is properly defined.