Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands ; Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands.
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
PLoS One. 2013 Dec 23;8(12):e83339. doi: 10.1371/journal.pone.0083339. eCollection 2013.
When using rats in pain research, strain-related differences in outcomes of tests for pain and nociception are acknowledged. However, very little is known about the specific characteristics of these strain differences. In this study four phylogenetically distant inbred rat strains, i.e. Wistar Kyoto (WKY), Fawn Hooded (FH), Brown Norway (BN) and Lewis (LE), were investigated in different tests related to pain and nociception. During Pavlovian fear conditioning, the LE and WKY showed a significantly longer duration of freezing behaviour than the FH and BN. Additionally, differences in c-Fos expression in subregions of the prefrontal cortex and amygdala between rat strains during retrieval and expression of conditioned fear were found. For example, the BN did not show recruitment of the basolateral amygdala, whereas the WKY, FH and LE did. During the hot plate test, the WKY and LE showed a lower thermal threshold compared to the BN and FH. In a follow-up experiment, the two most contrasting strains regarding behaviour during the hot plate test and Pavlovian fear conditioning (i.e. FH and WKY) were selected and the hot plate test, Von Frey test and somatosensory-evoked potential (SEP) were investigated. During the Von Frey test, the WKY showed a lower mechanical threshold compared to the FH. When measuring the SEP, the FH appeared to be less reactive to increasing stimulus intensities when considering both peak amplitudes and latencies. Altogether, the combined results indicate various differences between rat strains in Pavlovian fear conditioning, nociception related behaviours and nociceptive processing. These findings demonstrate the necessity of using multiple rat strains when using tests including noxious stimuli and suggest that the choice of rat strains should be considered. When selecting a strain for a particular study it should be considered how this strain behaves during the tests used in that study.
当在疼痛研究中使用大鼠时，人们承认不同品系大鼠在疼痛和伤害感受测试结果方面存在差异。然而，对于这些品系差异的具体特征，人们知之甚少。在这项研究中，我们研究了四种进化上相距甚远的近交系大鼠，即 Wistar 京都（WKY）、法恩霍德（FH）、布朗挪威（BN）和刘易斯（LE），它们在与疼痛和伤害感受相关的不同测试中表现出不同的特征。在巴甫洛夫恐惧条件反射中，LE 和 WKY 的冻结行为持续时间明显长于 FH 和 BN。此外，还发现了不同品系大鼠在恐惧条件反射的检索和表达过程中，前额叶皮层和杏仁核的不同亚区的 c-Fos 表达差异。例如，BN 没有招募基底外侧杏仁核，而 WKY、FH 和 LE 则有招募。在热板测试中，WKY 和 LE 的热阈值比 BN 和 FH 低。在后续实验中，选择了在热板测试和巴甫洛夫恐惧条件反射中行为表现最具对比性的两种品系（即 FH 和 WKY），并研究了热板测试、von Frey 测试和体感诱发电位（SEP）。在 von Frey 测试中，WKY 的机械阈值比 FH 低。在测量 SEP 时，FH 似乎对增加的刺激强度反应较低，无论是考虑峰值幅度还是潜伏期。总之，综合结果表明，在巴甫洛夫恐惧条件反射、伤害感受相关行为和伤害感受处理方面，不同大鼠品系之间存在各种差异。这些发现表明，在使用包括伤害性刺激的测试时，必须使用多个大鼠品系，并且应该考虑大鼠品系的选择。在为特定研究选择品系时，应该考虑该品系在该研究中使用的测试中的行为表现。
