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: 8075638
• 负责人: Jarred W. Younger
• 金额: $ 24.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8075638
• 关键词: Absence of pain sensation; Acute; Adverse effects; Adverse event; Affect; American; Analgesics; Animals; Award; Behavioral; Brain; Brain region; Development; Drug Metabolic Detoxication; Educational process of instructing; Experimental Designs; Feedback; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Human; Hyperalgesia; Imaging Techniques; Individual; Link; Longitudinal Studies; Maintenance; Mediating; Medication Management; Methods; Nature; Neurologic; Neurophysiology - biologic function; Opioid; Opioid Analgesics; Outcome; Pain; Pain management; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Phase; Process; Rehabilitation therapy; Research; Research Design; Role; Scanning; Series; Sex Characteristics; Site; Stimulus; Structure; Techniques; Testing; Time; Training; United States; Work; behavior measurement; chronic pain; gray matter; neural model; neuromechanism; programs; relating to nervous system; response; white matter

Opioid analgesics are some of the most commonly prescribed medications in the United States, and are being Increasingly used for chronic pain management. The use of opioids for chronic pain is concerning, given that the drugs are linked to a number of adverse events when used daily, including increased sensitivity to pain (hyperalgesia). 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 present powerful methods for exploring central mechanisms of pain. In the ROO independent research phase of his award. Dr. Younger will conduct a series of studies designed to systematically identify and test central neural mechanisms and substrates of opioid-induced hyperalgesia. The aims will be completed via three projects. Project #1 will extend pilot work carried out in the K99 phase of the award, and will examine the central neural correlates of opioid-induced hyperalgesia in opioid-naTve chronic pain patients. In the longitudinal study, changes in gray and white matter structure, functional response, and functional connectivity between brain regions will be assessed. Those neural changes will then be correlated with behavioral and self-report indicators of opioid-induced hyperalgesia, to determine how brain changes mediate increased pain sensitivity. Project #2 will describe the long-term neural effects of prolonged opioid exposure by examining brain structure and function in opioid-maintained chronic pain patients before and after an opioid detoxification and rehabilitation program. Project #3 will use rtfMRI to experimentally test the role of specific brain structures in the development and maintenance of opioid-induced hyperalgesia. Overarching, secondary goals of all projects are to examine gender differences in the neural response to opioids, and identify individuals who are most at hsk of developing opioid-induced hyperalgesia.

阿片类镇痛药是美国最常见的药物，并且是 越来越多地用于慢性疼痛管理。使用阿片类药物来慢性疼痛， 鉴于这些药物每天使用时与许多不良事件有关，包括增加 对疼痛的敏感性（痛觉过敏）。对动物和人类的研究表明，这种阿片类药物诱导 痛觉过敏是通过中央神经塑性变化介导的。实验设计仅限于 动物受试者由于其侵入性，并且需要表征阿片类药物诱导的 人类的痛苦。新技术，例如实时功能磁共振成像（RTFMRI） 允许对人参与者的中枢神经活动进行实验，无创调节，并 因此，提出了探索疼痛中心机制的强大方法。在Roo独立 他奖励的研究阶段。年轻博士将进行一系列旨在系统识别的研究 并测试阿片类药物诱导的痛觉过敏的中央神经机制和底物。目的将是 通过三个项目完成。项目＃1将扩展在奖项的K99阶段进行的试点工作，并将 将检查阿片类药物慢性疼痛中阿片类药物诱导的痛觉过敏的中心神经相关性 患者。在纵向研究中，灰质和白质结构，功能反应以及 将评估大脑区域之间的功能连通性。这些神经变化将相关 使用阿片类药物诱导的痛觉过敏的行为和自我报告指标，以确定大脑的变化 介导疼痛敏感性增加。项目2将描述长期阿片类药物的长期神经作用 通过检查阿片类药物维护的慢性疼痛患者的大脑结构和功能来暴露 经过阿片类药物排毒和康复计划。项目＃3将使用RTFMRI实验测试 特定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。 所有项目的总体，次要目标是检查神经反应中的性别差异 阿片类药物，并识别出开发阿片类药物诱导的痛觉过敏的HSK中最多的个体。