An industry perspective on the role and utility of animal models of pain in drug discovery
An industry perspective on the role and utility of animal models of pain in drug discovery
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从行业角度看疼痛动物模型在药物发现中的作用和效用
DOI：
10.1016/j.neulet.2013.08.033
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发表时间：
2013
影响因子：
2.5
通讯作者：
J. Kennedy
中科院分区：
文献类型：
--
作者：
G. Whiteside;J. Pomonis;J. Kennedy
近年来，动物行为模型，特别是用于疼痛研究的动物行为模型，由于其在慢性疼痛的新型药物治疗中的不良作用而受到越来越多的审查和批评。本文从工业药物发现研究的角度讨论了疼痛动物模型的使用。它强调了如何，何时以及为什么疼痛的动物模型被用作许多实验工具之一，用于更好地了解目标机制和排名顺序化合物在建立结构活性关系（SAR）的迭代过程中。总之，这些模型有助于为化合物创建“镇痛特征”，并告知最有可能在临床试验中取得成功的适应症。此外，作者还讨论了目前使用的（传统）疼痛动物模型的一些经常被低估的方面，包括行业如何平衡疗效与副作用措施，作为疗效总体结论的一部分。这是为了增加关于目前在啮齿动物和大型动物物种中开发新模型和终点以及评估疼痛的认知和/或情感方面的努力的观点。最后，作者提出了疼痛动物模型（无论是传统的还是新的）的疗效评价可能更好地与临床分析标准保持一致的方法，引用了将效应量和NNT估计应用于动物模型数据的例子，表明疗效标准通常可能在临床前设置得太低，无法成功转化为临床环境。
In recent years, animal behavioral models, particularly those used in pain research, have been increasingly scrutinized and criticized for their role in the poor translation of novel pharmacotherapies for chronic pain. This article addresses the use of animal models of pain from the perspective of industrial drug discovery research. It highlights how, when, and why animal models of pain are used as one of the many experimental tools used to gain better understanding of target mechanisms and rank-order compounds in the iterative process of establishing structure–activity relationships (SAR). Together, these models help create an ‘analgesic signature’ for a compound and inform the indications most likely to yield success in clinical trials. In addition, the authors discuss some often under-appreciated aspects of currently used (traditional) animal models of pain, including how industry balances efficacy with side effect measures as part of the overall conclusion of efficacy. This is provided to add perspective regarding current efforts to develop new models and endpoints both in rodents and larger animal species as well as assess cognitive and/or affective aspects of pain. Finally, the authors suggest ways in which efficacy evaluation in animal models of pain, whether traditional or new, might better align with clinical standards of analysis, citing examples where applying effect size and NNT estimations to animal model data suggest that the efficacy bar often may be set too low preclinically to allow successful translation to the clinical setting
影响因子：
13.8
作者：
Mao J
通讯作者：
Mao J
影响因子：
6.1
作者：
Stevenson, Glenn W.;Cormier, Jim;Mercer, Hannah;Adams, Chloe;Dunbar, Catherine;Negus, S. Stevens;Bilsky, Edward J.
通讯作者：
Bilsky, Edward J.