Opiate-Induced Tolerance & Hyperalgesia in Pain Patients

阿片类药物引起的耐受性

• 批准号: 7118009
• 负责人: LAWRENCE F CHU
• 金额: $ 13.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118009
• 关键词: backache; blood tests; chronic disease /disorder; chronic pain; clinical research; clinical trials; computer assisted patient care; disease /disorder model; disease /therapy duration; drug administration rate /duration; drug metabolism; drug tolerance; drug withdrawal; fentanyl; gender difference; human subject; hyperalgesia; morphine; nervous system disorder chemotherapy; opiate alkaloid; patient oriented research; questionnaires; racial /ethnic difference

DESCRIPTION (provided by applicant): This research proposal describes a 5-year plan for the development of an academic career in patient-oriented clinical pain research. The goal of this career development proposal is to expand the applicant' s scientific skills through mentored training in pain, clinical pharmacology, and epidemiologic research in order to become a successful independently-funded clinical scientist. The Candidate: Larry F. Chu, MD, MS is an Assistant Professor (appointment pending) in the Department of Anesthesia at the Stanford University School of Medicine. His short-term career goal is to obtain additional training in the principles and practice of clinical pain research through close research mentorship and formal training in clinical epidemiology. His long-term career goal is to develop a patient-oriented research program that focuses on characterizing neuroplastic changes associated with the pharmacologic treatment of chronic pain. Research Environment: Dr. Chu will be mentored by Dr. David Clark, Assistant Professor and Chief of the Palo Alto VA Pain Service, who will provide expertise in clinical pain management and pain research techniques. To enhance the training, Dr. Steven Shafer will provide expertise in the principles of clinical pharmacology. Dr. Shafer is an internationally-recognized investigator in clinical pharmacology who has a long and productive history of training postdoctoral fellows and mentoring junior clinical scientists. Formal didactic training in the principles of clinical research will be provided through completion of Stanford's K30 Clinical Research Training Program. Dr. Chu has been accepted into the 45-unit program, which will be completed over two years and result in a Master's Degree in Clinical Epidemiology. In addition, an interdisciplinary advisory committee of accomplished scientists and clinical researchers will provide additional scientific and career guidance. Research Plan: The applicant's research will focus on characterizing neuroplastic changes associated with chronic opioid therapy in patients with chronic pain. Opiates such as morphine are the cornerstone medications for the treatment of moderate to severe pain. Recent evidence suggests that pain patients on chronic opioid therapy become more sensitive to pain (hyperalgesia) over time. There is also a long-standing notion that analgesic tolerance to opioids (habituation) develops during chronic use even though this phenomenon has never been prospectively studied. Our specific aims propose to prospectively test the hypotheses that; 1) Pain patients on chronic opioid therapy develop dose-dependent tolerance and/or hyperalgesia to these medications over time, 2) Opioid-induced tolerance and hyperalgesia develop differently with respect to various types of pain, 3) Opioid-induced hyperalgesia occurs independently of withdrawal phenomena, and 4) Opioid-induced tolerance and hyperalgesia develop differently based on gender and/or ethnicity. This proposed study will be the first quantitative and prospective study of tolerance and hyperalgesia in pain patients and will have important implications for the rational use of opioids in the treatment of chronic pain.

描述（由申请人提供）： 该研究建议描述了一个为期5年的计划，以发展为患者的临床疼痛研究。这项职业发展建议的目的是通过疼痛，临床药理学和流行病学研究的指导培训来扩大申请人的科学技能，以成为一名成功的独立临床科学家。 候选人：马里兰州医学博士Larry F. Chu是斯坦福大学医学院麻醉系的助理教授（任命）。他的短期职业目标是通过密切的研究指导和临床流行病学的正式培训获得临床疼痛研究原理和实践的额外培训。他的长期职业目标是制定以患者为导向的研究计划，该计划的重点是表征与慢性疼痛药物治疗相关的神经塑性变化。研究环境：Chu博士将由Palo Alto Va Pain Service助理教授兼负责人David Clark博士指导，他将提供临床疼痛管理和疼痛研究技术方面的专业知识。为了增强培训，史蒂文·沙弗（Steven Shafer）博士将提供临床药理学原理的专业知识。 Shafer博士是临床药理学领域的国际认可的研究者，在培训博士后研究员和指导初级临床科学家方面拥有悠久而富有成效的历史。通过完成Stanford的K30临床研究培训计划，将提供有关临床研究原理的正式教学培训。 Chu博士已被接受为45个单位计划，该计划将在两年内完成，并获得临床流行病学硕士学位。此外，成熟的科学家和临床研究人员的跨学科咨询委员会将提供其他科学和职业指导。 研究计划：申请人的研究将着重于表征与慢性疼痛患者慢性阿片类药物治疗相关的神经塑性变化。鸦片（例如吗啡）是治疗中度至严重疼痛的基石药物。最近的证据表明，随着时间的流逝，慢性阿片类药物治疗的疼痛患者对疼痛（痛风）变得更加敏感。还有一个长期的观念，即在长期使用过程中对阿片类药物（习惯）的镇痛耐受性即使从未有过前瞻性研究过这种现象。我们的具体目的建议前瞻性检验的假设； 1）慢性阿片类药物治疗的疼痛患者会随着时间的推移对这些药物产生剂量依赖性耐受性和/或超痛觉过敏，2）阿片类药物诱导的耐受性和痛觉过敏性在各种类型的疼痛方面的发展不同，3）阿片类药物诱导的痛力症是独立于戒断现象，以及4）阿片类药物诱导的耐受性和痛觉过敏的发展基于性别和/或种族的发展不同。这项拟议的研究将是对疼痛患者耐受性和女痛性的首次定量和前瞻性研究，并将对阿片类药物在治疗慢性疼痛方面的合理使用具有重要意义。