EFFECTS AND MECHANISMS OF CHRONIC ELECTROACUPUNCTURE FOR EMESIS

描述（申请人提供）：癌症是一组以异常细胞不受控制的生长和扩散为特征的疾病。每年有超过一百万人患癌症。大约每两个美国男性中就有一个和每三个美国女性中就有一个会在他们一生中的某个时候患上某种癌症。顺铂是癌症化疗中最常用的药物之一。然而，化疗引起的严重不良事件，主要是恶心和呕吐，对患者来说可能比未来对预期寿命的担忧更令人痛苦。事实上，一些患者因为严重的顺铂引起的恶心和呕吐而选择停止潜在的治疗。止吐剂是治疗癌症患者化疗引起的恶心和呕吐最常见的干预措施。止吐治疗的基础是对呕吐的神经化学控制。然而，目前对于化疗引起的呕吐，尤其是迟发性呕吐，还没有令人满意的治疗方法。针刺或电针（EA）已被用于治疗化疗引起的恶心和呕吐。最近的一项荟萃分析表明，当与止吐药物联合应用时，通过插入针对穴位进行电刺激可有效减少急性呕吐。该项目的长期目标是开发一种有效的EA方法来治疗化疗引起的恶心和呕吐患者。在这个项目中，我们提出了一种创新的慢性EA方法，通过在穴位长期植入电极和放置在腹部皮肤下的可植入脉冲发生器来传递。利用这种新方法，EA可以方便地按需或连续地由患者提供。该项目将进行系统研究，以优化EA方法（最佳EA位置和最佳增产参数）。慢性EA对治疗化疗引起的呕吐有效的假设将在使用异食癖（食用粘土）的啮齿动物模型中进行测试。还将进行机制研究，以验证EA是通过迷走神经通路介导的假设，并涉及中枢神经递质、多巴胺和血清素。慢性EA在控制长期顺铂引起的急性和迟发性呕吐中的可行性、安全性和有效性也将进行研究。组建了一支由中医、胃肠电刺激、中枢神经系统生理学和医疗器械专家组成的竞争团队。

DESCRIPTION (provided by applicant): Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. Over one million people get cancer each year. Approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during their lifetime. Cisplatin is one of the most commonly used drugs in chemotherapy for cancers. However, severe adverse events resulting from chemotherapies, mainly nausea and vomiting may be much more distressing to a patient than future concerns of life expectancy. In fact, some patients choose to discontinue potentially curative therapy because of severe Cisplatin-induced nausea and vomiting. Antiemetic agents are the most common intervention in the management of chemotherapy-induced nausea and vomiting in cancer patients. The basis for antiemetic therapy is the neurochemical control of vomiting. However, currently, there are no satisfactory therapies for treating chemotherapy-induced emesis, especially delayed emesis. Acupuncture or electroacupuncture (EA) has been applied for treating chemotherapy-induced nausea and vomiting. A recent meta-analysis has indicated that electrical stimulation of the acupoint via inserted needles is effective in reducing acute vomiting when applied in combination with the anti-emetic medications. The long-term aim of this project is to develop an effective EA method to treat patients with chemotherapy-induced nausea and vomiting. In this project, we propose an innovative method of chronic EA delivered via chronically implanted electrodes at acupoints and an implantable pulse generator placed underneath the abdominal skin. With this new method, EA can be delivered on-demand conveniently by the patient or continuously. Systematic studies will be performed in this project to optimize the methodology of EA (best EA locations and optimal stimulation parameters). The hypothesis that chronic EA is effective in treating chemotherapy-induced emesis will be tested in a rodent model using pica (consumption of clay). Mechanistic studies will also be performed to test the hypotheses that EA is mediated via the vagal neuronal pathway and involves central neurotransmitters, dopamine and serotonin. The feasibility, safety and efficacy of chronic EA in controlling acute and delayed emesis induced by long-term cisplatin will also be investigated. A competitive team has been established, including experts in Traditional Chinese Medicine, gastrointestinal electrical stimulation, physiology of the central nervous system and medical device. PUBLIC HEALTH RELEVANCE: Chemotherapy-induced emesis is one of major problems in the treatment of patients with cancer and occurs in more than 90% of cases with certain medications, such as Cisplatin. With the recent advancement of anti-emetic medications, acute emesis is better controlled; however, delayed emesis remains a big challenge. A novel method of chronic electroacupuncture using implantable electrodes and stimulator is proposed in this project for the treatment of chemotherapy-induced emesis. Preliminary data supports this novel concept and experiments are designed to test the feasibility of the proposed method.