Biobehavioral Medicine in Oncology Program, Univ. Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Physiol Behav. 2012 Jun 25;106(4):562-8. doi: 10.1016/j.physbeh.2012.03.031. Epub 2012 Apr 4.
Although partially controlled with antiemetic drugs, postoperative nausea and vomiting (PONV) continues to be a problem for many patients. Clinical research suggests that opioid analgesics and volatile anesthetics are the main triggers of PONV. The aim of this study was to develop an animal model for post-anesthesia vomiting for future studies to further determine mechanisms and preclinical drug efficacy. Ferrets (N=34) were initially used because they have served as a gold standard for emesis research. Ferrets were tested with several doses of morphine, inhaled isoflurane, and a positive control injection of cisplatin (a chemotherapy agent) to induce emesis. Musk shrews (a small animal model; N=36) were also tested for emesis with isoflurane exposure. A control injection of cisplatin produced emesis in ferrets (ip, 129.8±22.0 retches; 13.7±2.3 vomits; mean±SEM). Morphine also produced a dose-response on emesis in ferrets, with maximal responses at 0.9 mg/kg (sc, 29.6±12.6 retches; 1.8±0.9, vomits). Isoflurane exposure (2-4% for 10 min to 6h exposure) failed to induce vomiting, was not associated with an increased frequency in emesis when combined with a low dose of morphine (0.1 mg/kg, sc), and failed to produce consistent effects on food and water intake. In contrast to ferrets, musk shrews were very sensitive to isoflurane-induced emesis (0.5 to 3%, 10 min exposure; up to 11.8±2.4 emetic episodes). Overall, these results indicate that ferrets will not be useful for delineating mechanisms responsible for isoflurane-induced emesis; however, musk shrews may prove to be a model for vomiting after inhalation of volatile agents.
尽管术后恶心和呕吐（PONV）可以通过止吐药物部分控制，但仍是许多患者面临的问题。临床研究表明，阿片类镇痛药和挥发性麻醉剂是 PONV 的主要触发因素。本研究旨在开发一种用于麻醉后呕吐的动物模型，以便未来的研究进一步确定机制和临床前药物疗效。雪貂（N=34）最初被用于该研究，因为它们一直是呕吐研究的金标准。研究人员用几种剂量的吗啡、吸入异氟烷和阳性对照顺铂（一种化疗药物）对雪貂进行了测试，以诱导呕吐。还用异氟烷暴露对麝鼠（一种小动物模型；N=36）进行了呕吐测试。顺铂（ip，129.8±22.0 次干呕；13.7±2.3 次呕吐；均值±SEM）的对照注射可引起雪貂呕吐。吗啡也在雪貂中产生了呕吐的剂量反应，最大反应发生在 0.9mg/kg（sc，29.6±12.6 次干呕；1.8±0.9 次呕吐）。异氟烷暴露（2-4%，暴露 10 分钟至 6 小时）未能引起呕吐，与低剂量吗啡（0.1mg/kg，sc）联合使用时，与呕吐频率增加无关，也不能对食物和水的摄入产生一致的影响。与雪貂相反，麝鼠对异氟烷引起的呕吐非常敏感（0.5 至 3%，10 分钟暴露；多达 11.8±2.4 次呕吐发作）。总体而言，这些结果表明，雪貂对于阐明异氟烷引起呕吐的机制将没有用；然而，麝鼠可能是挥发性麻醉剂吸入后呕吐的模型。
