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Musk shrews selectively bred for motion sickness display increased anesthesia-induced vomiting

机译:选择性繁殖麝香sh的晕车展示增加麻醉诱导的呕吐

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摘要

Susceptibility to motion sickness is a predictor of postoperative nausea and vomiting, and studies in humans suggest that genetic factors determine sensitivity to motion sickness. The aim of the current study was to determine if a preclinical model could be selectively bred for motion-induced emesis and to assess a potential relationship to anesthesia-induced emesis. Musk shrews were tested for motion-induced emesis using a shaker plate (10 min, 1 Hz, and 4 cm of lateral displacement). Animals were rank ordered for motion-induced emesis and selectively bred to produce high and low response strains. Shrews were also tested with nicotine (5 mg/kg, sc), copper sulfate (CuSO4; 120 mg/kg, ig), and isoflurane anesthesia (10 min; 3%) to determine responses to a panel of emetic stimuli. High response strain shrews demonstrated significantly more emetic responses to motion exposure compared to low response strain animals in the F1 and F2 generations. In F2 animals, there were no significant differences in total emetic responses or emetic latency between strains after nicotine or CuSO4 injection. However, isoflurane exposure stimulated more emesis in F1 and F2 high versus low strain animals, which suggests a relationship between vestibular- and inhalational anesthesia-induced emesis. Overall, these results indicate genetic determinants of motion sickness in a preclinical model and a potential common mechanism for motion sickness and inhalational anesthesia-induced emesis. Future work may include genetic mapping of potential “emetic sensitivity genes” to develop novel therapies or diagnostics for patients with high risk of nausea and vomiting.
机译:晕动病的易感性是术后恶心和呕吐的预兆,人类研究表明,遗传因素决定了晕动病的敏感性。当前研究的目的是确定是否可以为运动诱发的呕吐选择性地培养临床前模型,并评估与麻醉诱发的呕吐的潜在关系。使用振动板(10分钟,1 Hz和4 cm的横向位移)测试麝香sh的运动​​诱发呕吐。对动物进行运动诱发的呕吐的等级排序,并有选择地繁殖以产生高和低应答株。还使用尼古丁(5 mg / kg,sc),硫酸铜(CuSO4; 120 mg / kg,ig)和异氟烷麻醉(10分钟; 3%)对进行测试,以确定对一组催吐剂的反应。与F1和F2代中的低响应菌株动物相比,高响应菌株sh表现出对运动暴露的催吐反应明显更多。在F2动物中,尼古丁或CuSO4注射后菌株之间的总催吐反应或催吐潜伏期之间无显着差异。然而,与低应变动物相比,异氟烷暴露在F1和F2高应变动物中刺激了更多的呕吐,这提示前庭麻醉和吸入麻醉诱导的呕吐之间存在关联。总体而言,这些结果表明在临床前模型中晕动症的遗传决定因素以及晕动症和吸入麻醉引起的呕吐的潜在共同机制。未来的工作可能包括对潜在的“催吐敏感性基因”进行基因定位,以开发出针对恶心和呕吐高风险患者的新疗法或诊断方法。

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