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

基本信息

批准号：
7499003
负责人：
Jarred W. Younger
金额：
$ 8.71万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7499003
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 Magnetic Resonance Imaging 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

项目摘要

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.

项目摘要：基于阿片类药物的镇痛药的长期给药与发展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是通过中央神经塑性变化介导的。实验设计受到限制由于动物受试者的侵入性，因此有必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，提出了一种探索疼痛中心机制的强大方法。我们提出了一个全面的培训计划和随后的研究计划，涉及阿片类药物诱导的机制 Hypergesia，包括使用RTFMRI实验设计。在这笔赠款的K99培训阶段，博士年轻人将在斯坦福大学医学院训练，在医学博士肖恩·麦基的指导下博士学位，一位既定的疼痛研究员，以及一支合作导师团队，包括加里·格洛弗（Gary Glover），博士（放射学），医学博士David Clark（阿片类药物诱导的Hypergesia）和Ravi Prasad，PhD（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，进度评论进行由指导委员会定期出席校长和讲习班以及教学机会。这随后的ROD独立研究阶段涉及一系列旨在系统识别的研究并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。我们的第一个目的是表征阿片类药物诱导的痛觉过敏的中心神经相关性。其次，我们建议描述长期接触阿片类药物的长期神经作用。最后，我们将使用RTFMRI实验测试角色阿片类药物诱导的痛觉过敏的开发和维持中的特定大脑结构。相关性：慢性疼痛影响美国数百万个人，其中很大一部分处方阿片类镇痛药。长期使用阿片类药物可能会提高患者的敏感性疼痛，增加了疼痛的原始抱怨，并使疾病进展的情况感到困惑。这是重要的是要了解大脑如何参与这种增加的疼痛敏感性以及长期的长期影响这些变化可能会有。