Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse
Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse
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DOI：
10.1016/j.pain.2006.03.023
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发表时间：
2006-09-01
期刊：
影响因子：
7.4
通讯作者：
Mogil, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Green, Amanda D.;Young, Katrina K.;Mogil, Jeffrey S.
瘙痒在人类中具有相当大的个体间变异性，使用动物模型的初步研究已经证明遗传因素在介导这种变异性中可能起作用。在试图系统地研究遗传介导的瘙痒在小鼠中，这样的基因识别的连锁图谱可能会实现，我们研究了抓挠行为引起的组胺和氯喹的小鼠I I近交系小鼠。使用多个氯喹药物剂量，揭示了每个菌株中存在倒U型剂量-反应关系，使我们能够确定整个剂量范围内的菌株依赖性峰刮擦行为。在这组品系中，氯喹诱导的抓挠峰值变化为2.5倍;抓挠行为在小鼠中显示出中度遗传性。目前的数据还首次揭示了维生素E诱导的抓挠行为的显著性别差异，雌性小鼠抓挠的平均次数比雄性多23%。最后，这里获得的应变手段与以前收集的数据使用伤害性试验的比较揭示了氯喹诱导的瘙痒和热痛之间的暗示性负遗传相关性，这样的菌株敏感的疼痛是耐痒，反之亦然。这一发现可能对我们理解瘙痒病理生理学和识别瘙痒相关基因都有意义。(c)2006年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Itch features considerable interindividual variability in humans, and initial studies using animal models have demonstrated a likely role of genetic factors in mediating such variability. In an attempt to systematically study genetic mediation of itch in the mouse such that gene identification by linkage mapping might be achieved, we examined scratching behavior induced by histamine and chloroquine in mice of I I inbred mouse strains. Multiple chloroquine drug doses were used, revealing the existence of inverted-U dose-response relationships in every strain, allowing us to determine strain-dependent peak scratching behavior over the entire dose range. Peak chloroquine-induced scratching varied by 2.5-fold in this set of strains; scratching behavior shows moderate heritability in the mouse. The present data also reveal, for the first time, significant sex differences in pruritogen-induced scratching behavior, with female mice scratching an average of 23% more than males. Finally, a comparison of the strain means obtained here with previously collected data using nociceptive assays revealed a suggestive negative genetic correlation between chloroquine-induced itch and thermal pain, such that strains sensitive to pain are resistant to itch and vice versa. This finding may have implications both for our understanding of itch pathophysiology and for the identification of itch-related genes. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.