Most pre-clinical
analgesic efficacy assays still involve nociceptive testing in rodents. This is despite concerns as to the relevance of these tests for evaluating the
pain-preventative properties of drugs. More appropriate methods would target
pain rather than nociception, but these are currently not available, so it remains unknown whether animal
pain equates to the negatively affective and subjective/emotional state it causes in humans. Mouse
cancer models are common despite the likelihood of substantial
pain. We used Conditioned Place Preference (
CPP) testing, assessments of
thermal hyperalgesia and behaviour to determine the likelihood that MBT-2
bladder cancer impacts negatively on mouse welfare, such as by causing
pain. There was no
CPP to saline, but
morphine preference in tumour bearing mice exceeded that seen in tumour-free controls. This occurred up to 10 days before the study end-point alongside reduced
body weight, development of
hyperalgesia and behaviour changes. These effects indicated mice experienced a negative welfare state caused by malaise (if not
pain) before
euthanasia. Due to the complexity of the assessments needed to demonstrate this, it is unlikely that this approach could be used for routine welfare assessment on a study-by-study basis. However, our results show mice in sufficiently similar studies are likely to benefit from more intensive severity assessment and re-evaluation of end-points with a view to implementing appropriate refinements. In this particular case, a refinement would have been to have euthanased mice at least 7 days earlier or possibly by provision of end-stage
pain relief.
CPP testing was found to be a helpful method to investigate the responses of mice to
analgesics, possibly on a subjective level. These findings and those of other recent studies show it could be a valuable method of screening candidate
analgesics for efficacy against
cancer pain and possibly other
pain or disease models.