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

项目摘要：长期给予阿片类镇痛药与 对疼痛的敏感性增加。对动物和人类的研究表明，这种阿片类药物- 诱导的痛觉过敏通过中枢神经可塑性变化介导。实验设计受到限制 由于其侵入性，因此需要表征阿片类药物诱导的动物受试者 痛觉过敏新技术如实时功能性磁共振成像（rtfMRI） 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调节， 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 全面的培训计划和随后的研究计划，以阿片类药物诱导的机制， 痛觉过敏，包括使用rtfMRI实验设计。在K99培训阶段，博士。 杨格将在医学博士肖恩·麦基的指导下，在斯坦福大学医学院接受培训， 博士，一个既定的疼痛研究者，以及一个团队的合作导师，包括加里格洛弗，博士 （放射学），大卫克拉克，医学博士，博士（阿片类药物诱导的痛觉过敏）和拉维普拉萨德，博士（临床心理学）。 培训将通过正式课程、动手实验室培训、指导研究、进度审查进行 由指导委员会定期举办座谈会和讲习班，并提供教学机会。的 随后的ROD独立研究阶段包括一系列旨在系统地识别 并测试中枢神经结构在阿片诱导的痛觉过敏中的作用。我们的首要目标是 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来实验性地测试这种作用， 阿片类药物引起的痛觉过敏的发展和维持中的特定脑结构。 相关性：慢性疼痛影响着美国数百万人，其中很大一部分人 给个人开阿片类镇痛药。长期使用阿片类药物可能会增加患者的敏感性 疼痛，增加了原来的疼痛投诉和混淆疾病进展的图片。是 重要的是，我们要了解大脑是如何参与这种增加的疼痛敏感性，以及长期 这些变化可能带来的影响。

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-timefunctional 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.