Reported analgesic administration to rabbits undergoing experimental surgical procedures

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (<it>P </it>< 0.001). Papers that reported ethical approval were more likely than papers that did not specify approval to report systemic analgesic administration (<it>P </it>< 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.</p> <p>Conclusions</p> <p>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.</p

Determining candidate hypobaric hypoxia profiles for humane killing of laboratory mice

Millions of mice are used annually in scientific research and must be humanely killed. Despite significant welfare concerns, carbon dioxide exposure remains the most common killing method, primarily because there is no practical and humane alternative. We explored whether hypobaric hypoxia via gradual decompression could induce a non-recovery state in anesthetized male C57BL/6 and Balb/c laboratory mice. We aimed to determine if this was possible in a feasible timescale with minimal pathological consequences, as a proof-of-principle step. Systematic evaluation of two decompression rates (75, 150 ms(−1)) and three profile shapes (accelerated, linear, gradual) in a factorial design revealed that hypobaric hypoxia effectively induced a non-recovery state in anesthetized laboratory mice, irrespective of decompression rate and shape. Mice took longer to reach a non-recovery state with the 75 ms(−1) decompression rate (75 ms(−1): 257 ± 8.96 vs. 150 ms(−1): 214 ± 7.26 s), with longer latencies in gradual and linear shaped profiles. Accelerated shaped profiles were least susceptible to meaningful refinement via rate. The only pathological changes of concern were moderate middle ear congestion and hemorrhage. These findings suggest that hypobaric hypoxia has potential, and subsequent work will evaluate the welfare consequences of gradual decompression in conscious mice, to identify decompression profiles that minimize welfare harms associated with ear barotrauma

Resolving Animal Distress and Pain: Principles and Examples of Good Practice in Various Fields of Research

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation. This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress dichotomy by adopting a holistic treatment of adverse effects, i.e., not parsing distress and pain, by providing guidance on how to assess deviations from normality through tools such as score sheets. Our aim is to provide practical information to IACUCs, scientists, technicians and animal care personnel. We organize the chapter according to specific research areas and case studies. However, the principles and approaches are readily generalized to other research areas. CONTENTS Effect of surgical technical skill on pain and distress in animals - Alicia Karas, DVM Carbon dioxide euthanasia: example of aversion techniques - Matthew C. Leach, PhD The Refinement of Infectious Disease Research - Karl A. Andrutis DVM, MS, DACLAM Polyclonal antibody production - Kathleen Conlee, BS, MPA Animal models of human psychopathology: anxiety - John P. Gluck PhD Refinement In Toxicology Testing: A Workshop to Promote Current Advances and Disseminate Best Practices - Andrew N. Rowan, Martin L. Stephens, and Kathleen M. Conle

Negative mood affects the expression of negative but not positive emotions in mice

Whether and to what extent animals experience emotions is crucial for understanding their decisions and behaviour, and underpins a range of scientific fields, including animal behaviour, neuroscience, evolutionary biology and animal welfare science. However, research has predominantly focused on alleviating negative emotions in animals, with the expression of positive emotions left largely unexplored. Therefore, little is known about positive emotions in animals and how their expression is mediated. We used tail handling to induce a negative mood in laboratory mice and found that while being more anxious and depressed increased their expression of a discrete negative emotion (disappointment), meaning that they were less resilient to negative events, their capacity to express a discrete positive emotion (elation) was unaffected relative to control mice. Therefore, we show not only that mice have discrete positive emotions, but that they do so regardless of their current mood state. Our findings are the first to suggest that the expression of discrete positive and negative emotions in animals is not equally affected by long-term mood state. Our results also demonstrate that repeated negative events can have a cumulative effect to reduce resilience in laboratory animals, which has significant implications for animal welfare

Ample evidence for fish sentience and pain

The majority of commentaries are supportive of our position on the scepticism that muddies the waters surrounding fish pain and sentience. There is substantial empirical evidence for pain in fish. Animals’ experience of pain cannot be compared to artificial intelligence (AI) because AI can only mimic responses to nociceptive input on the basis of human observations and programming. Accepting that fish are sentient would not be detrimental to the industries reliant on fish. A more proactive discussion between scientists and stakeholders is needed to improve fish welfare for the benefit of all

Opportunities for refinement in neuroscience: Indicators of wellness and post-operative pain in laboratory macaques

Being able to assess pain in nonhuman primates undergoing biomedical procedures is important for preventing and alleviating pain, and for developing better guidelines to minimise the impacts of research on welfare in line with the 3Rs principle of Refinement. Nonhuman primates are routinely used biomedical models however it remains challenging to recognise negative states, including pain, in these animals. This study aimed to identify behavioural and facial changes that could be used as pain or general wellness indicators in the rhesus macaque (Macaca mulatta). Thirty-six macaques scheduled for planned neuroscience procedures were opportunistically monitored at four times: Pre-Operative (PreOp), Post-Operative (PostOp) once the effects of anaesthesia had dissipated, Pre-Analgesia (PreAn) on the subsequent morning prior to repeating routine analgesic treatment, and Post-Analgesia (PostAn) following administration of analgesia. Pain states were expected to be absent in PreOp, moderate in PreAn, and mild or absent in PostOp and PostAn when analgesia had been administered. Three potential pain indicators were identified: lip tightening and chewing, which were most likely to occur in PreAn, and running which was least likely in PreAn. Arboreal behaviour indicated general wellness, while half-closed eyes, leaning of the head or body shaking indicated the opposite. Despite considerable individual variation, behaviour and facial expressions could offer important indicators of pain and wellness and should be routinely quantified, and appropriate interventions applied to prevent or alleviate pain, and promote positive welfare

The Assessment of Post-Vasectomy Pain in Mice Using Behaviour and the Mouse Grimace Scale

Background: Current behaviour-based pain assessments for laboratory rodents have significant limitations. Assessment of facial expression changes, as a novel means of pain scoring, may overcome some of these limitations. The Mouse Grimace Scale appears to offer a means of assessing post-operative pain in mice that is as effective as manual behavioural-based scoring, without the limitations of such schemes. Effective assessment of post-operative pain is not only critical for animal welfare, but also the validity of science using animal models. Methodology/Principal Findings: This study compared changes in behaviour assessed using both an automated system (‘‘HomeCageScan’’) and using manual analysis with changes in facial expressions assessed using the Mouse Grimace Scale (MGS). Mice (n = 6/group) were assessed before and after surgery (scrotal approach vasectomy) and either received saline, meloxicam or bupivacaine. Both the MGS and manual scoring of pain behaviours identified clear differences between the pre and post surgery periods and between those animals receiving analgesia (20 mg/kg meloxicam or 5 mg/kg bupivacaine) or saline post-operatively. Both of these assessments were highly correlated with those showing high MGS scores also exhibiting high frequencies of pain behaviours. Automated behavioural analysis in contrast was only able to detect differences between the pre and post surgery periods. Conclusions: In conclusion, both the Mouse Grimace Scale and manual scoring of pain behaviours are assessing th

Fish sentience denial: Muddying the waters

Recent empirical studies have reported evidence that many aquatic species, including fish, cephalopods and crustaceans, have the capacity for nociception and pain, and that their welfare should be taken into consideration. Some sceptics, rejecting the precautionary principle, have denied that any study demonstrates pain or other aspects of sentience in fish. This target article discusses some of the scientific shortcomings of these critiques through a detailed analysis of a study exploring nociception and analgesia in larval zebrafish