Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation
Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation
复制标题
DOI：
10.1038/laban.1223
复制
发表时间：
2017-04-01
期刊：
影响因子：
6.9
通讯作者：
Mogil, Jeffrey S.
中科院分区：
文献类型：
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作者：
Mogil, Jeffrey S.
近几十年来，基础到临床转化的不良记录导致人们猜测临床前研究是“不可复制的”，而这种不可复制性又在很大程度上归因于报告和统计实践的缺陷。然而，对于一个实验室在复制另一个实验室的结果时翻译不佳和困难，还有一些其他合理的解释。本文探讨这些解释，因为它们属于临床前疼痛研究。我认为，许多明显的不可重复性的情况下，实际上是由于研究中的现象和干预措施之间的相互作用和“潜在的”环境因素影响啮齿动物的科目。这些环境变量通常会引起压力，并与畜牧业和特定的测试环境有关，在实验室之间差异很大，并继续被识别，这表明我们对它们的存在的了解还远远不够。特别是在疼痛研究中，实验室应激源可以产生不可预测方向的巨大变化，因为已知应激会根据其参数产生疼痛的增加（应激诱导的痛觉过敏）或减少（应激诱导的镇痛）。如果要改进复制和翻译，就需要更加重视对实验室环境的研究。
The poor record of basic-to-clinical translation in recent decades has led to speculation that preclinical research is "irreproducible", and this irreproducibility in turn has largely been attributed to deficiencies in reporting and statistical practices. There are, however, a number of other reasonable explanations of both poor translation and difficulties in one laboratory replicating the results of another. This article examines these explanations as they pertain to preclinical pain research. I submit that many instances of apparent irreproducibility are actually attributable to interactions between the phenomena and interventions under study and "latent" environmental factors affecting the rodent subjects. These environmental variables-often causing stress, and related to both animal husbandry and the specific testing context -differ greatly between labs, and continue to be identified, suggesting that our knowledge of their existence is far from complete. In pain research in particular, laboratory stressors can produce great variability of unpredictable direction, as stress is known to produce increases (stress-induced hyperalgesia) or decreases (stress-induced analgesia) in pain depending on its parameters. Much greater attention needs to be paid to the study of the laboratory environment if replication and translation are to be improved.