Mechanisms of Opioid-Induced Hyperalgesia in Pain Patients: Examination via fMRI

阿片类药物引起疼痛患者痛觉过敏的机制：通过功能磁共振成像检查

• 批准号: 7302152
• 负责人: Jarred W. Younger
• 金额: $ 8.65万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7302152
• 关键词: Absence of pain sensation; Acute; Affect; Analgesics; Animals; Behavioral; Brain; Brain region; Chronic; Classification; Clinical; Clinical Psychology; Condition; Cues; Development; Disease Progression; Doctor of Philosophy; Educational process of instructing; Educational workshop; Etiology; Experimental Designs; Family; Feedback; Functional Magnetic Resonance Imaging; Future; Grant; Hand; Human; Hyperalgesia; Individual; Invasive; Lead; Literature; Long-Term Effects; Maintenance; Mediating; Mentors; Methods; Nature; Neurologic; Neurophysiology - biologic function; Opioid; Opioid Analgesics; PAG gene; Pain; Participant; Patients; Pharmaceutical Preparations; Phase; Population; Process; Radiology Specialty; Reaction; Research; Research Design; Research Personnel; Role; Score; Series; Site; Societies; Stimulus; Structure; Techniques; Technology; Testing; Time; Training; Translating; United States; Universities; Withdrawal; base; behavior measurement; chronic pain; human PAG protein; medical schools; neural model; neuromechanism; programs; relating to nervous system; research study; response; retinal rods

DESCRIPTION (provided by applicant): Project Summary: Chronic administration of opioid-based analgesics has been associated with the development of increased sensitivity to pain. Research in both animals and humans suggest that this opioid induced hyperalgesia is mediated via central, neuroplastic changes. Experimental designs have been limited to animal subjects because of their invasive nature, and there is a need to characterize opioid-induced hyperalgesia in humans. New techniques such as real-time functional magnetic resonance imaging (rtfMRI) allow for the experimental, non-invasive modulation of central nervous activity in human participants and therefore presents a powerful method for exploring central mechanisms of pain. We propose a comprehensive training plan and subsequent research program into the mechanisms of opioid-induced hyperalgesia, including the use of rtfMRI experimental designs. In the K99 training phase of this grant, Dr. Younger will train at the Stanford University School of Medicine, under the direction of Sean Mackey, MD, PhD, an established pain researcher, as well as a team of collaborating mentors, including Gary Glover, PhD (radiology), David Clark, MD, PhD (opioid-induced hyperalgesia) and Ravi Prasad, PhD (clinical psychology). Training will be conducted via formal coursework, hands-on lab training, mentored research, progress review by the steering committee, regular attendance of colloquia and workshops, and teaching opportunities. The subsequent ROD independent research phase involves a series of studies designed to systematically identify and test the role of central neural structures in opioid-induced hyperalgesia. Our first aim is to characterize the central neural correlates of opioid-induced hyperalgesia in humans. Second, we propose to describe the long-term neural effects of prolonged opioid exposure. Last, we will use rtfMRI to experimentally test the role of specific brain structures in the development and maintenance of opioid-induced hyperalgesia. Relevance: Chronic pain affects millions of individuals in the United States, and a large proportion of these individuals are prescribed opioid analgesics. The long-term use of opioids may increase patients' sensitivity to pain, adding to the original complaints of pain and confusing the picture of disease progression. It is important that we understand how the brain is involved in this increased pain sensitivity and what long-term impact these changes may have.

描述（由申请人提供）：项目总结：长期给予阿片类镇痛药与疼痛敏感性增加相关。动物和人类的研究表明，阿片类药物诱导的痛觉过敏是通过中枢神经可塑性变化介导的。由于其侵入性，实验设计仅限于动物受试者，并且需要表征阿片类药物诱导的人类痛觉过敏。实时功能性磁共振成像（rtfMRI）等新技术允许对人类参与者的中枢神经活动进行实验性、非侵入性调制，因此为探索疼痛的中枢机制提供了一种强有力的方法。我们提出了一个全面的培训计划和后续的研究计划阿片类药物引起的痛觉过敏的机制，包括使用rtfMRI实验设计。在K99培训阶段，Younger博士将在斯坦福大学医学院接受培训，由Sean Mackey博士指导，Sean Mackey博士是一位知名的疼痛研究人员，以及一组合作导师，包括加里格洛弗博士（放射学），大卫克拉克博士（阿片类药物引起的痛觉过敏）和拉维普拉萨德博士（临床心理学）。培训将通过正式的课程作业，动手实验室培训，指导研究，指导委员会的进度审查，定期参加座谈会和研讨会以及教学机会进行。随后的ROD独立研究阶段涉及一系列旨在系统地识别和测试阿片类药物诱导的痛觉过敏中中枢神经结构的作用的研究。我们的第一个目标是描述阿片类药物诱导的人类痛觉过敏的中枢神经相关性。其次，我们建议描述长期阿片类药物暴露的长期神经效应。最后，我们将使用rtfMRI实验测试特定的大脑结构在阿片类药物诱导的痛觉过敏的发展和维持中的作用。相关性：慢性疼痛影响着美国数百万人，其中很大一部分人被处方阿片类镇痛药。长期使用阿片类药物可能会增加患者对疼痛的敏感性，增加最初的疼痛症状，并混淆疾病进展的情况。重要的是，我们要了解大脑如何参与这种增加的疼痛敏感性，以及这些变化可能产生的长期影响。