The effects of Ojeok-san on neuro-immune interactions in cancer-induced visceral pain

项目摘要 内脏疼痛是晚期癌症患者最常见的疼痛类型之一。这是 很大程度上由炎症水平升高介导。阿片衍生药物仍然是首选处方 用于癌症引起的疼痛的止痛剂，尽管它们诱导肠道生态失调、耐受性、肝和肾毒性， 和阿片类药物引起的痛觉过敏。由于这些原因，必须确定补充疗法， 治疗内脏疼痛Ojeok-san是一种东方草药配方，通常用于亚洲国家的抗- 炎性、免疫调节和镇痛特性。然而，它对癌症引起的内脏 疼痛尚未得到检查。长期目标是开发草药配方Ojeok-san作为临床 延迟和/或预防癌症引起的内脏疼痛的可测试的饮食方案。短期目标是 确定Ojeok-san在癌症诱导的临床前模型中的益处和作用机制 内脏疼痛中心假设是Ojeok-san通过极化来减轻癌症引起的内脏疼痛 巨噬细胞的抗炎表型和降低TNF α。这一假设将在三个 相关但独立的目标。具体目标1将评估Ojeok-san对癌症引起的内脏 疼痛;具体目标2将确定Ojeok-san是否影响巨噬细胞极化和与 感觉神经元在癌症引起的内脏痛;和具体目标3将检查是否止痛 Ojeok-san在癌症诱导的内脏疼痛中的作用是通过细胞因子TNFα介导的。统称 建议的研究将阐明Ojeok-san对癌症引起的内脏疼痛的作用机制。 了解草药配方的机制，如Ojeok-san，可以作为止痛药， 这对开发致力于减轻内脏疼痛的新疗法至关重要。研究- 本K99/R 00建议书中的培训计划包括多方面的指导和辅导， 综合健康、免疫学和神经科学。总的来说，培训计划，导师， 顾问，外部咨询委员会，南卡罗来纳州大学的丰富环境 包括补充和替代医学中心，膳食补充剂中心， 炎症，和结肠癌研究中心，将是我成功过渡到 他是癌症疼痛补充医学领域的独立科学家。

PROJECT SUMMARY Visceral pain is among the most frequent type of pain experienced by patients with advanced cancer. This is largely mediated by elevated levels of inflammation. Opioid-derived drugs remain the preferred prescribed analgesic for cancer-induced pain despite their induction of gut dysbiosis, tolerance, liver and kidney toxicity, and opioid-induced hyperalgesia. For these reasons it is imperative to identify complementary therapies to treat visceral pain. Ojeok-san is an oriental herbal formula, commonly used in Asian countries for its anti- inflammatory, immunoregulatory, and analgesic properties. However, its effects on cancer-induced visceral pain have not yet been examined. The long-term goal is to develop the herbal formula Ojeok-san as a clinically testable dietary regimen to delay and/or prevent cancer-induced visceral pain. The short-term goal is to determine the benefits and mechanisms of action of Ojeok-san in a preclinical model of cancer-induced visceral pain. The central hypothesis is that Ojeok-san attenuates cancer induced visceral pain by polarizing macrophages to an anti-inflammatory phenotype and decreasing TNF. This hypothesis will be tested in three related, but independent aims. Specific Aim 1 will assess the benefits of Ojeok-san on cancer-induced visceral pain; Specific Aim 2 will determine whether Ojeok-san influences macrophage polarization and interaction with sensory neurons in cancer-induced visceral pain; and Specific Aim 3 will examine whether the analgesic effects of Ojeok-san in cancer induced visceral pain are mediated through the cytokine TNFα. Collectively, the proposed studies will elucidate the mechanism of action of Ojeok-san on cancer-induced visceral pain. Understanding the mechanism by which an herbal formula, such as Ojeok-san, can serve as an analgesic is of critical importance to the development of novel treatments dedicated to alleviate visceral pain. The research- training plan in this K99/R00 proposal includes multifaceted guidance and mentoring on complementary and integrative health, immunology, and neuroscience. Taken together, the training plan, the Mentors, the Consultants, the External Advisory Committee, the enriched environment at the University of South Carolina including the Center for Complementary and Alternative Medicine, Center of Dietary Supplements and Inflammation, and the Center for Colon Cancer Research, will be fundamental for my successful transition to an independent scientist in the field of complementary medicine in cancer pain.