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

阿片类止痛药是美国最常见的处方药物之一， 越来越多地被用于慢性疼痛治疗。使用阿片类药物治疗慢性疼痛令人担忧， 鉴于这些药物在日常使用时与许多不良事件有关，包括增加 对疼痛敏感(痛觉过敏)。对动物和人类的研究表明，这种阿片类药物导致 痛觉过敏是通过中枢神经可塑性改变来调节的。实验设计已经被限制在 由于动物的侵袭性，有必要对阿片类药物诱导的 人类的痛觉过敏。实时功能磁共振成像(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的、非侵入性的调节 因此，提出了探索疼痛中枢机制的有力方法。在Roo独立的 他获奖的研究阶段。杨格博士将进行一系列研究，旨在系统地确定 并测试阿片类药物诱导的痛敏的中枢神经机制和底物。目标将是 通过三个项目完成。项目1将延长在K99阶段开展的试点工作，以及 将研究阿片类药物引起的慢性疼痛的痛敏反应的中枢神经关系 病人。在纵向研究中，灰质和白质结构、功能反应和 将评估大脑区域之间的功能连接。然后这些神经变化将被关联起来 用阿片类药物引起的痛觉过敏的行为和自我报告指标来确定大脑的变化 调节疼痛敏感度的增加。项目2将描述长期阿片类药物对神经的长期影响 阿片类药物维持性慢性疼痛患者在治疗前和治疗前的脑结构和功能暴露 在阿片类药物戒毒和康复计划之后。项目3将使用rtfMRI对 特定脑结构在阿片类药物诱导的痛敏发生和维持中的作用。 总而言之，所有项目的次要目标是检查神经反应中的性别差异 阿片类药物，并确定哪些人最容易发生阿片类药物诱导的痛觉过敏。

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.