Advancing and refining euthanasia methods in laboratory rodents

绝大多数实验室啮齿类动物（大鼠和小鼠）在研究项目结束时被杀死。这个过程是人道的，提供一个快速的，无痛的死亡（“安乐死”）。不幸的是，随着我们对动物行为和生理的了解越来越多，目前的方法是否真正实现安乐死还不清楚。两种最常见的方法是过量使用二氧化碳气体和过量使用吸入或注射麻醉药物。每种方法都存在一些问题：1。动物在二氧化碳气体的作用下会失去意识，这一点还没有得到证实。在此之前，有可能会经历疼痛（二氧化碳刺激气道）。2. 啮齿类动物对吸入的麻醉气体感到厌恶。原因尚不清楚。3. 过量注射麻醉剂通常会导致昏迷和迅速死亡。然而，在多达20%的啮齿类动物中，注射的药物最终落在了错误的地方，在昏迷发生之前有一段时间的延迟。由于麻醉溶液是强碱的，在这段时间内可能会发生疼痛。我的研究项目侧重于了解这些不同的方法如何影响实验室啮齿动物。这项研究的目的是确定疼痛是否可能在动物失去知觉之前发生，并找到更好的方法，以实现安乐死。我们使用的工具包括通过评估面部表情和监测脑电波活动（脑电图）来评估疼痛的存在，以寻找疼痛和死亡的迹象。我期望找到一种新的安乐死方法，并通过更好地了解现有方法的优点和局限性，对现有方法进行改进。所使用和开发的评估方法将适用于评估未来的安乐死方法。这项研究的结果对我们如何管理加拿大以及国际上实验室啮齿动物的临终关怀具有重要而深远的影响，具有改善每年数百万动物护理的潜力（在欧盟，加拿大和英国之间每年有超过1500万只啮齿动物用于生物医学研究）。此外，这项研究将为自然科学、工程和兽医专业的学生提供研究培训，为他们在大学、临床实践和工业领域的职业生涯做好准备。

The overwhelming majority of laboratory rodents (rats and mice) are killed when research projects end. This process is intended to be humane, providing a rapid, pain-free death ("euthanasia"). Unfortunately, as we understand more about animal behaviour and physiology, it is unclear if current methods truly achieve euthanasia. Two of the most common methods are overdose with carbon dioxide gas and overdose with an inhaled or injected anesthetic drug. There are concerns about each of these methods: 1. The point at which animals become unconscious with carbon dioxide gas is not well-established. It is possible that pain (carbon dioxide irritates the airways) is experienced before this occurs. 2. Rodents find inhaled anesthetic gas aversive. The cause of this is unknown. 3. Overdose with injected anesthetic usually causes unconsciousness and death quickly. However, in up to 20% of rodents, the injected drug ends up in the wrong place and there is a delay before unconsciousness occurs. It is possible that pain occurs during this delay as the anesthetic solution is strongly alkali. My program of research focuses upon understanding how these different methods affect laboratory rodents. The goal of this research is to identify if pain may be occurring before animals become unconscious and to find better methods, with the aim of achieving euthanasia. Tools we use include assessing the presence of pain by evaluating facial expression and monitoring brain wave activity (electroencephalograms) for signs of pain and death. I anticipate identifying both a novel euthanasia method and also offering refinements to existing methods through a better understanding of their strengths and limitations. The assessment methods used and developed will be applicable to evaluating future euthanasia methods. The results of this research have important and far reaching consequences for how we manage end of life care for laboratory rodents within Canada but also internationally, with the potential to improve care for millions of animals annually (in excess of 15 million rodents are used in biomedical research annually between the EU, Canada and the UK). Additionally, this research will provide research training for students from the natural sciences, engineering and veterinary medicine, preparing them for careers in universities, clinical practice and industry.