Departments of Psychology and Anesthesia and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
Lab Anim (NY). 2017 Mar 22;46(4):136-141. doi: 10.1038/laban.1223.
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.
近几十年来，基础到临床转化的记录不佳，导致人们猜测临床前研究是“不可重现的”，而这种不可重现性在很大程度上归因于报告和统计实践的缺陷。然而，对于基础研究中较差的转化和一个实验室难以复制另一个实验室的结果，还有许多其他合理的解释。本文探讨了这些解释与临床前疼痛研究的相关性。我认为，许多明显不可重现的情况实际上是由于研究中的现象和干预之间的相互作用以及影响啮齿动物的“潜在”环境因素造成的。这些环境变量——通常会导致压力，与动物饲养和特定的测试环境有关——在实验室之间差异很大，并且仍在不断被发现，这表明我们对它们存在的认识还远远不够。特别是在疼痛研究中，实验室压力源会产生难以预测方向的巨大变异性，因为压力会根据其参数导致疼痛增加（应激诱导性痛觉过敏）或减少（应激诱导性镇痛）。如果要提高复制和转化的成功率，就需要更加关注实验室环境的研究。
