Fish Physiology: analgesics and their side effects

鱼类生理学：镇痛药及其副作用

• 批准号: RGPIN-2015-04214
• 负责人: Stevens, E
• 金额: $ 2.04万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=665943
• 关键词: Fish; Physiology; analgesics; their; side

***We focus on two areas of fish physiology: analgesics and their side effects.****Analgesia: The goal here is to understand the ways that fish respond to a noxious ("painful") stimulus and how drugs modify that response. Life science researchers in Canada use as many fish as either rats or mice. The Canadian Council for Animal Care (CCAC) "Guidelines for Use of Fish in Research" does not contain specific recommendations for the use of analgesics ("pain killers") because we do not have sufficient information to make the appropriate recommendations. Our laboratory tests some fundamental assumptions regarding analgesics and analgesia in fish. We develop tests that can be used to produce dose-response curves (that is, how much drug is required to get an effect) for analgesics and measure how long they are effective. We have done this for morphine and now propose to do it for other analgesics. The question of whether or not fish can "feel pain" is a very difficult one. In our experiments, we look for a response to a stimulus that would be considered painful to humans or other mammals. Here we propose to study the effect of sea lice and the wounds they cause on fish behavior and see if the behavior is modified by local anesthetics, if behavior is modified by substances secreted by the sea lice, and if so, the mechanisms the sea lice use to modify the fish behavior. We also will test the effects of analgesics on fish behavior associated with wounds that occur when implanting telemetry devices. This work is important because it likely will influence CCAC policy.******Side effects of local anesthetics - their effects on mitochondrial energetics. It has been known for some time that systemic administration of local anesthetics results in cytotoxic side effects, especially on cardiac tissue and nervous tissue. Different mechanisms have been proposed for the cytotoxic effects, but most evidence points to the effect being at the mitochondrial level. The mitochondrion is the organelle present in all cells that is responsible for supplying energy in the form of ATP for that cell to balance its energy use in order to support cell function. Previous studies show that local anesthetics depress aerobic respiration of mitochondria and cells. My overall aim in these experiments is to measure the effects of local anesthetics on cell and mitochondrial energetics from fish tissues and to unveil the mechanisms accounting for their effects. I will focus on three local anesthetics: lidocaine and bupivacaine (because these are the drugs that have been suggested by veterinarians and other researchers that we use with fish) and tricaine (because this is the drug most often used to anesthetize fish).********

* 我们专注于鱼类生理学的两个领域：镇痛剂及其副作用。*镇痛：这里的目标是了解鱼类对有害（“痛苦”）刺激的反应方式以及药物如何改变这种反应。加拿大的生命科学研究人员使用的鱼类数量与大鼠或小鼠一样多。加拿大动物保护理事会（CCAC）“研究中使用鱼类的指导方针”不包含使用镇痛剂（“止痛药”）的具体建议，因为我们没有足够的信息来提出适当的建议。我们的实验室测试一些关于鱼的镇痛剂和镇痛的基本假设。我们开发的测试可用于产生镇痛药的剂量反应曲线（即需要多少药物才能产生效果），并测量它们的有效时间。我们已经对吗啡做了这一点，现在建议对其他镇痛药也做这一点。鱼是否能“感觉到疼痛”是一个非常困难的问题。在我们的实验中，我们寻找对刺激的反应，这种反应被认为是人类或其他哺乳动物的痛苦。在这里，我们建议研究海虱的影响，他们对鱼的行为造成的伤口，看看行为是否被局部麻醉剂修改，如果行为被修改的物质分泌的海虱，如果是这样，机制的海虱使用修改鱼的行为。我们还将测试止痛剂对鱼行为的影响，这些鱼行为与植入遥测装置时发生的伤口有关。这项工作很重要，因为它可能会影响廉政公署的政策。局部麻醉药的副作用-它们对线粒体能量的影响。一段时间以来，人们已经知道局部麻醉剂的全身给药会导致细胞毒性副作用，特别是对心脏组织和神经组织。已经提出了细胞毒性效应的不同机制，但大多数证据表明该效应是在线粒体水平上。线粒体是存在于所有细胞中的细胞器，负责以ATP的形式为该细胞提供能量，以平衡其能量使用，以支持细胞功能。以往的研究表明，局麻药抑制线粒体和细胞的有氧呼吸。在这些实验中，我的总体目标是测量局部麻醉剂对鱼类组织细胞和线粒体能量学的影响，并揭示其作用机制。我将重点介绍三种局部麻醉剂：利多卡因和布比卡因（因为这些是兽医和其他研究人员建议用于鱼类的药物）和三卡因（因为这是最常用于麻醉鱼类的药物）。