Ngampramuan Sukonthar, Cerri Matteo, Del Vecchio Flavia, Corrigan Joshua J, Kamphee Amornrat, Dragic Alexander S, Rudd John A, Romanovsky Andrej A, Nalivaiko Eugene
Research Center for Neuroscience and Institute of Molecular Bioscience, Mahidol University, Bangkok, Thailand.
Oncotarget. 2014 Mar 30;5(6):1565-75. doi: 10.18632/oncotarget.1732.
Nausea is a prominent symptom and major cause of complaint for patients receiving anticancer chemo- or radiation therapy. The arsenal of anti-nausea drugs is limited, and their efficacy is questionable. Currently, the development of new compounds with anti-nausea activity is hampered by the lack of physiological correlates of nausea. Physiological correlates are needed because common laboratory rodents lack the vomiting reflex. Furthermore, nausea does not always lead to vomiting. Here, we report the results of studies conducted in four research centers to investigate whether nausea is associated with any specific thermoregulatory symptoms. Two species were studied: the laboratory rat, which has no vomiting reflex, and the house musk shrew (Suncus murinus), which does have a vomiting reflex. In rats, motion sickness was induced by rotating them in their individual cages in the horizontal plane (0.75 Hz, 40 min) and confirmed by reduced food consumption at the onset of dark (active) phase. In 100% of rats tested at three centers, post-rotational sickness was associated with marked (1.5°C) hypothermia, which was associated with a short-lasting tail-skin vasodilation (skin temperature increased by ~4°C). Pretreatment with ondansetron, a serotonin 5-HT3 receptor antagonist, which is used to treat nausea in patients in chemo- or radiation therapy, attenuated hypothermia by ~30%. In shrews, motion sickness was induced by a cyclical back-and-forth motion (4 cm, 1 Hz, 15 min) and confirmed by the presence of retching and vomiting. In this model, sickness was also accompanied by marked hypothermia (2°C). Like in rats, the hypothermic response was preceded by transient tail-skin vasodilation. In conclusion, motion sickness is accompanied by hypothermia that involves both autonomic and thermoeffector mechanisms: tail-skin vasodilation and possibly reduction of the interscapular brown adipose tissue activity. These thermoregulatory symptoms may serve as physiological correlates of nausea.
恶心是接受抗癌化疗或放疗患者的一个突出症状和主要主诉原因。抗恶心药物的种类有限，其疗效也存在疑问。目前，由于缺乏恶心的生理相关指标，具有抗恶心活性的新化合物的研发受到阻碍。之所以需要生理相关指标，是因为常见的实验啮齿动物缺乏呕吐反射。此外，恶心并不总是会导致呕吐。在此，我们报告了在四个研究中心进行的研究结果，以调查恶心是否与任何特定的体温调节症状相关。我们研究了两个物种：没有呕吐反射的实验大鼠，以及确实有呕吐反射的家麝鼩（Suncus murinus）。在大鼠中，通过在其单独的笼子里在水平面上旋转（0.75Hz，40分钟）来诱发晕动病，并通过在黑暗（活跃）期开始时食物摄入量减少来确认。在三个中心测试的100%的大鼠中，旋转后疾病与显著（约1.5°C）的体温过低相关联，这与短暂的尾皮血管舒张有关（皮肤温度升高约4°C）。用昂丹司琼（一种5-羟色胺5-HT3受体拮抗剂，用于治疗化疗或放疗患者的恶心）进行预处理，可使体温过低减轻约30%。在麝鼩中，通过周期性的来回运动（4厘米，1Hz，15分钟）来诱发晕动病，并通过干呕和呕吐的出现来确认。在这个模型中，疾病也伴有显著的体温过低（约2°C）。与大鼠一样，体温过低反应之前有短暂的尾皮血管舒张。总之，晕动病伴有体温过低，这涉及自主神经和体温调节效应机制：尾皮血管舒张以及可能肩胛间棕色脂肪组织活动的减少。这些体温调节症状可能作为恶心的生理相关指标。
