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

描述(由申请人提供)：项目摘要：长期服用阿片类止痛药与疼痛敏感性的提高有关。在动物和人类中的研究表明，这种阿片类药物诱导的痛敏是通过中枢神经可塑性改变来调节的。由于其侵袭性，实验设计仅限于动物受试者，因此有必要对阿片类药物诱导的人类痛觉过敏进行表征。实时功能磁共振成像(RtfMRI)等新技术允许对参与者的中枢神经活动进行实验性的、非侵入性的调制，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阿片类药物诱导痛敏机制的研究计划，包括使用rtfMRI的实验设计。在这笔赠款的K99培训阶段，杨格博士将在斯坦福大学医学院接受培训，指导老师是著名的疼痛研究人员肖恩·麦基，医学博士和博士，以及合作导师团队，包括加里·格洛弗(放射学博士)、大卫·克拉克(医学博士)、博士(阿片类药物引起的痛觉过敏)和拉维·普拉萨德(临床心理学)博士。培训将通过正式课程作业、动手实验室培训、指导研究、指导委员会的进度审查、定期出席座谈会和讲习班以及教学机会来进行。随后的Rod独立研究阶段涉及一系列研究，旨在系统地识别和测试中枢神经结构在阿片类药物诱导的痛觉过敏中的作用。我们的第一个目标是确定阿片类药物引起的人类痛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神经影响。最后，我们将使用rtfMRI来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：在美国，慢性疼痛影响着数百万人，其中很大一部分人是开阿片类止痛药的。长期使用阿片类药物可能会增加患者对疼痛的敏感性，增加最初对疼痛的抱怨，并混淆疾病进展的图景。重要的是，我们要了解大脑是如何参与这种疼痛敏感性增加的，以及这些变化可能会产生什么长期影响。

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.