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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.

项目总结：长期给药阿片类镇痛药与