Advancing and refining euthanasia methods in laboratory rodents

当研究项目结束时，绝大多数实验室啮齿动物(大鼠和小鼠)都会被杀死。这一过程是人道的，提供快速、无痛的死亡(“安乐死”)。不幸的是，随着我们对动物行为和生理有了更多的了解，目前还不清楚目前的方法是否真的实现了安乐死。最常见的两种方法是二氧化碳气体过量和吸入或注射麻醉药过量。人们对这些方法都有顾虑：1.动物对二氧化碳气体失去知觉的程度并不是很确定。疼痛(二氧化碳刺激呼吸道)有可能是在疼痛发生之前就经历过的。2.啮齿动物认为吸入麻醉剂气体是令人厌恶的。造成这种情况的原因尚不清楚。3.注射麻醉剂过量常导致昏迷和迅速死亡。然而，在多达20%的啮齿动物中，注射的药物最终到达了错误的位置，并且在昏迷之前有一段时间。由于麻醉液是强碱性的，所以在此延迟期间可能会出现疼痛。我的研究重点是了解这些不同的方法是如何影响实验室啮齿动物的。这项研究的目的是确定疼痛是否可能在动物失去意识之前发生，并找到更好的方法，目的是实现安乐死。我们使用的工具包括通过评估面部表情来评估疼痛的存在，以及监测脑波活动(脑电)以寻找疼痛和死亡的迹象。我期待通过更好地了解现有方法的优点和局限性，确定一种新的安乐死方法，并对现有方法进行改进。所使用和开发的评估方法将适用于对未来安乐死方法的评估。这项研究的结果对我们如何在加拿大国内以及国际上管理对实验室啮齿动物的临终关怀具有重要而深远的影响，有可能改善每年对数百万动物的护理(欧盟、加拿大和英国每年有超过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、临床实践和行业中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.