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

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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.