Reduction & refinement in animal models of neuropathic pain: using systematic review & meta-analysis

慢性疼痛的管理是一个严重影响患者生活质量的主要临床问题。神经病理性疼痛(NP)是一种常见的慢性疼痛，发生在感觉神经系统受损后，原因广泛，包括糖尿病、创伤、手术、癌症和自身免疫性疾病。目前的治疗方法往往不能为患者提供足够的疼痛缓解，或者有无法忍受的副作用。动物可以用来提高我们对疾病的理解，并测试新疗法的有效性。有许多不同的方法来模拟NP，这些动物会受到许多不同的测试，其中一些会引起更多的疼痛或痛苦。这项研究的主要目的是改进所使用的测试，以减少动物的痛苦和使用的动物数量。系统地确定所有可用的研究将提供在NP建模中使用的方法的范围的概述。将这些数据汇总在一起，将为我们提供高严重性测试的效用的直接证据，无论是否有必要进行多次测试，无论长期实验是否具有附加值，或者那些持续时间较短的实验是否有用，并将指导我们未来研究所需的动物数量。该项目将首次从已完成的NP实验中提供证据，以减少和改进动物在这一研究领域的使用。以前，在临床环境中将动物研究的结果转化为人类存在重大问题。我们已经证明，当你系统地审查研究时，往往会在设计、进行和报告方面存在缺陷。这些实验质量上的缺陷往往会导致研究夸大其发现的规模。使用数据集，我们将评估研究的质量以及这种质量对他们的发现的影响。在过去，人体临床试验中的类似缺陷导致了对其行为和监管的重大改革。不幸的是，进行实验室动物研究的相同标准并不存在；然而，对模拟神经疾病的动物研究的系统审查已经开始了类似的过程。这背后的推动力是对描述中风动物模型中质量下降和报道不足的影响的经验证据的回应。使用类似的技术和整理经验证据有可能改革和提高NP动物模型的实用性。在科学界，有一种发表积极结果的趋势。报道无影响或负面影响的研究通常不会发表。这种偏见导致了对一个研究领域的总结，比如所提出的，夸大了真实的效果。我们计划量化NP文献中出版偏见的存在和程度。如果实验室研究要用于改善人类健康，无论结果如何，它们的研究结果都必须是可靠的和可用的。综上所述，本研究将提供关于NP的所有动物研究的概述。这些数据将使我们能够评估与那些对动物造成较少疼痛和痛苦的测试相比，高严重性测试的有效性和实用性。此外，我们将能够量化不同持续时间的实验的价值，并潜在地改善这一研究领域中使用的动物的福利。描述研究的质量和范围将允许提供基于证据的指导方针，以改进NP动物研究的设计、实施和报告。量化公布偏差的大小将突显问题的严重性，并有望推动改革，以改善实验数据的公布。我们还计划向该领域的同事公开该数据库；这将减少不必要的重复实验。

The management of chronic pain is a major clinical problem that can severely affect the quality of life of sufferers. Neuropathic pain (NP), a common type of chronic pain, occurs after damage to the sensory nervous system and has a wide range of causes including diabetes, trauma, surgery, cancer and autoimmune disease. Current treatments often do not provide adequate pain relief for patients, or have intolerable side effects. Animals can be used to improve our understanding of a disease and to test the effectiveness of novel treatments. There are many different ways of modelling NP and these animals are subjected to many different tests, some of which cause more pain or distress than others. The main aim of this study is to refine the tests used in order to reduce the suffering of animals and to reduce the number of animals used.Systematically identifying all available studies will provide an overview of the range of methods used in the modelling of NP. Aggregating these data together will give us direct evidence of the utility of high severity tests, whether multiple tests are necessary, whether lengthy experiments are of added value or whether those of shorter duration areas useful and will guide us on the number of animals required for future studies. This project will, for the first time, provide evidence from completed experiments in NP to reduce and refine the use of animals in this field of research.Previously, there have been significant problems in translating findings from animal studies to humans in a clinical setting. We have shown that when you systematically scrutinise studies there are often flaws in their design, conduct and reporting. These shortcomings in the quality of experiments tend to result in studies exaggerating the magnitude of their findings. Using the dataset we will assess the quality of studies and the impact of this quality on their findings. In the past similar shortcomings in human clinical trials led to substantial reforms in their conduct and regulation. Unfortunately, the same standards for the conduct of laboratory animal studies do not exist; however, the systematic scrutiny of animal studies modelling neurological diseases has initiated the beginnings of a similar process. The impetus behind this is in response to the empirical evidence describing the impact of reduced quality and insufficient reporting in animal models of stroke. Using similar techniques and curating empirical evidence has the potential to reform and improve the utility of animal models of NP.Within the scientific community there is a tendency towards publishing positive results. Studies reporting no or negative effects are often not published. This bias results in summaries of a research field, such as the proposed, overstating true effects. We plan to quantify the presence and magnitude of publication bias in the NP literature. If laboratory studies are to be used to improve human health their findings need to be both reliable and available irrespective of the results. In summary, this study will provide an overview of all animal studies of NP. These data will allow us to assess the validity and utility of high severity tests in comparison to those inflicting less pain and distress to animals. In addition we will be able to quantify the value of varying durations of experiments and potentially improve the welfare of animals used in this field of research. Describing the quality and range of studies will allow to provide evidence based guidelines to improve the design, conduct and reporting of NP animal studies. Quantifying the magnitude of publication bias will highlight the severity of the problem and hopefully drive reform to improve the publicising of experimental data. We also plan to make the database publicly available for colleagues in the field; this will reduce unnecessary replication of experiments.