Finding effective analgesics in zebrafish by analysing effects on the nervous system (CNS)

通过分析对神经系统 (CNS) 的影响寻找斑马鱼的有效镇痛药

• 批准号: NC/L000237/1
• 负责人: Catherina Becker
• 金额: $ 9.4万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FL000237%2F1
• 关键词: Finding; effective; analgesics; zebrafish; analysing

The zebrafish is becoming increasingly popular in biomedical research (more than 400.000 individuals were used in 2011 according to the Home Office), as it is relatively small and still shares many features with other back-boned animals (vertebrates). This makes scientific findings from the zebrafish translatable for medical research. Adult and larval fish are being used in diverse fields, including research in cancer and neurodegenerative diseases and undergo potentially painful procedures, yet most procedures are done without proper analgesia (pain relief). This is mainly because not much is known about how fish process potentially harmful input. Efforts are underway to look, for example, at changes in behaviour after potentially painful experiences and how specific drugs (analgesics) mitigate these, in order to develop protocols for effective analgesia (pain relief) in fish. However, the central nervous system, which receives these stimuli, processes them and directs the behavioural changes, is not being analysed. We believe that analysing changes in the central nervous system is indispensable to directly demonstrate that harmful stimuli affect the brain, and that analgesic drugs are effective at the level of brain. In this pilot project, we aim to support efforts analysing behaviour and other parameters by finding changes in the activity of different genes in areas of the spinal cord and brain after potentially painful experiences. This will give direct information on the processing of such input. Moreover, by trying a number of potential analgesics we will determine which of these work most effectively by directly measuring gene activity in the brain. Our preliminary analyses show that application of mustard oil to muscle tissue leads to increased activity of genes in the spinal cord and brainstem that are often activated in the context of harmful stimuli. Ideally, we will find analgesics that block this reaction already at the level of the spinal cord, where stimuli are first processed. In subsequent research, our findings from the brain will be compared to data from behaviour and other non-invasive measures to determine optimal protocols for analgesia in fishes and derive non-invasive indicators of successful analgesia in future zebrafish research. Our data will thus help to refine experiments in fishes in the sense of Refinement as defined in the 3Rs, by devising protocols for analgesia that are supported by neurobiological observations and thus inform scientists and policy makers on best practice in fish experiments.

斑马鱼在生物医学研究中越来越受欢迎（根据内政部的数据，2011年使用了超过40万人），因为它相对较小，并且仍然与其他脊椎动物（脊椎动物）共享许多特征。这使得斑马鱼的科学发现可用于医学研究。成鱼和幼鱼被用于不同的领域，包括癌症和神经退行性疾病的研究，并经历潜在的痛苦程序，但大多数程序都没有适当的镇痛（疼痛缓解）。这主要是因为人们对鱼类如何处理潜在的有害输入知之甚少。例如，目前正在努力研究潜在痛苦经历后的行为变化以及特定药物（镇痛剂）如何减轻这些变化，以便制定鱼类有效镇痛（缓解疼痛）的方案。然而，接收这些刺激、处理它们并指导行为变化的中枢神经系统没有被分析。我们认为，分析中枢神经系统的变化对于直接证明有害刺激影响大脑以及镇痛药物在大脑水平有效是必不可少的。在这个试点项目中，我们的目标是通过发现脊髓和大脑区域中不同基因在潜在痛苦经历后的活动变化来支持分析行为和其他参数的努力。这将提供有关处理此类输入的直接信息。此外，通过尝试一些潜在的止痛药，我们将通过直接测量大脑中的基因活性来确定哪一种最有效。我们的初步分析表明，将芥子油应用于肌肉组织会导致脊髓和脑干中的基因活性增加，这些基因通常在有害刺激的情况下被激活。理想情况下，我们会在脊髓水平找到阻断这种反应的止痛药，脊髓是刺激首先被处理的地方。在随后的研究中，我们从大脑中的发现将与行为和其他非侵入性措施的数据进行比较，以确定鱼类镇痛的最佳方案，并在未来的斑马鱼研究中获得成功镇痛的非侵入性指标。因此，我们的数据将有助于在3R定义的精炼意义上完善鱼类实验，通过设计由神经生物学观察支持的镇痛协议，从而为科学家和政策制定者提供鱼类实验的最佳实践。