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

Ojeok-san 对癌症引起的内脏疼痛中神经免疫相互作用的影响

基本信息

批准号：
10004566
负责人：
Kandy T Velazquez
金额：
$ 24.9万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10004566
关键词：
Absence of pain sensation Advanced Malignant Neoplasm Advisory Committees Affect Afferent Neurons Analgesics Anti-Inflammatory Agents Applications Grants Asians Attenuated Automobile Driving Bone Marrow CSF1R gene Calcitonin Gene-Related Peptide Cancer Model Cancer Patient Chronic Clinical Coculture Techniques Colitis Colon Carcinoma Colorectal Complementary Health Complementary Medicine Complementary and alternative medicine Complementary therapies Country Data Development Diet Disease Dose Flow Cytometry Gastrointestinal Diseases Goals Hepatotoxicity Herpesvirus 1 Hyperalgesia Hypersensitivity Immunology In Vitro Infiltration Inflammation Inflammatory Integrative Medicine Interleukin-4 Interruption Intestines Irritable Bowel Syndrome Knock-out Lead Link Malignant Neoplasms Mediating Medicinal Herbs Mentors Modeling Mus Neuroimmune Neurons Neurosciences Nociception Opioid Pain Pain management Pancreatitis Pathway interactions Patients Pharmaceutical Preparations Phase Phenotype Physiological Play Pre-Clinical Model Preparation Process Property Public Health Regimen Research Research Training Scientist Sensory Serum Signal Transduction South Carolina Spinal Ganglia System TNF gene TNFRSF1A gene Techniques Testing Training Universities Visceral Visceral pain anticancer research cancer pain cancer therapy colorectal distension cytokine dietary supplements dysbiosis effective therapy environmental enrichment for laboratory animals experience immunoregulation macrophage mouse model nephrotoxicity novel overexpression prevent promoter response tumor necrosis factor-alpha inhibitor

Absence of pain sensation Advanced Malignant Neoplasm Advisory Committees Affect Afferent Neurons Analgesics Anti-Inflammatory Agents Applications Grants Asians Attenuated Automobile Driving Bone Marrow CSF1R gene Calcitonin Gene-Related Peptide Cancer Model Cancer Patient Chronic Clinical Coculture Techniques Colitis Colon Carcinoma Colorectal Complementary Health Complementary Medicine Complementary and alternative medicine Complementary therapies Country Data Development Diet Disease Dose Flow Cytometry Gastrointestinal Diseases Goals Hepatotoxicity Herpesvirus 1 Hyperalgesia Hypersensitivity Immunology In Vitro Infiltration Inflammation Inflammatory Integrative Medicine Interleukin-4 Interruption Intestines Irritable Bowel Syndrome Knock-out Lead Link Malignant Neoplasms Mediating Medicinal Herbs Mentors Modeling Mus Neuroimmune Neurons Neurosciences Nociception Opioid Pain Pain management Pancreatitis Pathway interactions Patients Pharmaceutical Preparations Phase Phenotype Physiological Play Pre-Clinical Model Preparation Process Property Public Health Regimen Research Research Training Scientist Sensory Serum Signal Transduction South Carolina Spinal Ganglia System TNF gene TNFRSF1A gene Techniques Testing Training Universities Visceral Visceral pain anticancer research cancer pain cancer therapy colorectal distension cytokine dietary supplements dysbiosis effective therapy environmental enrichment for laboratory animals experience immunoregulation macrophage mouse model nephrotoxicity novel overexpression prevent promoter response tumor necrosis factor-alpha inhibitor

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项目摘要

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.

项目摘要内脏疼痛是晚期癌症患者经常遭受的疼痛类型之一。这是在很大程度上是由炎症水平升高介导的。阿片类药物衍生的药物仍然是首选的处方癌症引起的疼痛的镇痛药使他们诱导肠道营养不良，耐受性，肝脏和肾脏毒性，和OioID诱导的痛觉过敏。由于这些原因，必须确定补充疗法治疗内脏疼痛。 Ojeok-san是东方草药配方，在亚洲国家常用炎症，免疫调节和镇痛特性。但是，它对癌症引起的内脏的影响尚未检查疼痛。长期目标是将草药式Ojeok-san开发为临床可测试的饮食方案延迟和/或预防癌症引起的内脏疼痛。短期目标是确定Ojeok-San在癌症诱导的临床前模型中的作用的好处和机制内脏疼痛。中心假设是，ojeok-san通过极化减轻了癌症引起的内脏疼痛巨噬细胞到抗炎表型并减少TNF。该假设将在三个相关，但独立目标。具体目标1将评估Ojeok-San对癌症引起的内脏的好处疼痛;特定的目标2将确定Ojeok-san是否影响巨噬细胞极化和与癌症引起的内脏疼痛的感觉神经元；和特定的目标3将检查镇痛药是否 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。集体，拟议的研究将阐明Ojeok-San对癌症引起的内脏疼痛的作用机理。了解诸如Ojeok-san之类的草药配方的机制可以用作镇痛药对于减轻内脏疼痛的新型治疗方法的发展至关重要。研究 - 该K99/R00建议中的培训计划包括多方面的指导和精神上的完整性和心理综合健康，免疫学和神经科学。综上所述，培训计划，导师，顾问，外部咨询委员会，南卡罗来纳大学丰富的环境包括互补和替代医学中心，饮食补品中心以及炎症和结肠癌研究中心将是我成功过渡到癌症疼痛中补充医学领域的独立科学家。