The conditioned place preference test for assessing welfare consequences and potential refinements in a mouse bladder cancer model.

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.

Are we looking in the wrong place? Implications for behavioural-based pain assessment in rabbits (Oryctolagus cuniculi) and beyond?

BACKGROUND: Successful observation of behaviour depends upon knowing both which behaviours to look for and focusing on the appropriate areas of the body to observe them. Behaviour based scoring systems have become increasingly widely used to assess animal pain and distress. Although studies are available demonstrating which behaviours need to be observed, there has been little attempt to assess how effectively observers apply such information when viewing an animal's behaviour. METHODOLOGY/PRINCIPAL FINDINGS: This study used historical video recordings of New Zealand white rabbits (Oryctolagus cuniculi) considered to be experiencing varying degrees of post-operative pain to assess the pattern of observation and the ability to assess pain exhibited by both experienced and inexperienced human participants (n = 151). Eye tracking equipment was used to identify how quickly, how frequently, for how long different areas of the rabbit's body were attended to by the participants. Simple visual analogue scoring was used to assess the pain experienced in each sequence. The results demonstrate that irrespective of their experience or gender, observers focus first, more frequently and for longer on the face, compared to the abdomen, ears, back and hindquarters of the rabbit and that participants were poor at identifying rabbits in pain. Observing the back and hindquarters was correlated with 'correct' assessments and observing the face was correlated with 'incorrect' assessments. CONCLUSIONS: In conclusion, irrespective of experience and gender, observers focused on the face when using behaviour to assess pain and were unable to effectively identify rabbits in pain. Focusing on the face is unlikely to be effective when using behavioural indicators of pain since they involve other body areas. Alternatively, if animals exhibit pain-related facial expressions, then it could improve our ability to assess pain. In addition, these results have potential implications for the use of behaviour to assess how rabbits and potentially other species feel.

Reported analgesic administration to rabbits undergoing experimental surgical procedures.

BACKGROUND: It has become widely accepted that whenever animals are used in scientific procedures, the 3Rs principle of replacement, reduction and refinement described by William Russell and Rex Burch should be adhered to. Animals should be replaced with non-sentient alternatives if possible, the number of animals used should be reduced and experimental procedures should be refined to minimise pain, suffering and distress. Administration of analgesic agents to animals undergoing surgical procedures is a refinement used to alleviate pain. In this study, a structured literature review was carried out to examine current trends in analgesic administration to rabbits undergoing experimental surgical procedures. RESULTS: 128 papers from 51 peer-reviewed journals were selected for inclusion in this review. Reporting administration of systemic analgesia to rabbits in peer-reviewed scientific papers increased significantly from 16% to 50% between 1995-1997 and 2005-2007 (P < 0.001). Papers that reported ethical approval were more likely than papers that did not specify approval to report systemic analgesic administration (P < 0.001). When systemic analgesics were administered, buprenorphine was the most frequently used agent and non-steroidal anti-inflammatory drugs were used less frequently than opioids in both time periods. CONCLUSIONS: Although this review provides evidence that systemic analgesic administration to rabbits undergoing surgical procedures is increasing, rabbits do not always receive analgesia when they undergo experimental surgery. Other practices in rabbit perioperative care that could be improved, highlighted by this survey include: 1) changing the timing of analgesic administration by giving systemic analgesics pre- or perioperatively rather than only postoperatively, 2) using multimodal analgesia when pain is likely to be moderate to severe and 3) increasing the use of non-steroidal anti-inflammatory drugs and use of other techniques such as epidural analgesia particularly for orthopaedic procedures.