The Impact of Opioids on Chronic Pain: Clinical Research and Career Training in Spinal Cord fMRI and Brain Reward Systems

阿片类药物对慢性疼痛的影响：脊髓功能磁共振成像和大脑奖励系统的临床研究和职业培训

• 批准号: 9977139
• 负责人: Katherine Theresa Martucci
• 金额: $ 24.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977139
• 关键词: Behavior; Behavior Therapy; Behavioral; Body Regions; Brain; Cervical spinal cord structure; Chronic; Clinical; Clinical Research; Clinical Trials Design; Cognition; Data; Depressed mood; Development; Disease; Doctor of Philosophy; Educational process of instructing; Effectiveness; Faculty; Fatigue; Fibromyalgia; Functional Magnetic Resonance Imaging; Funding; Goals; Hyperalgesia; Hypersensitivity; Individual; Knowledge; Lead; Learning; Long-Term Effects; Measures; Mentors; Methods; Nervous System Physiology; Neuraxis; Neurobiology; Neurologic; Neurons; Nociception; Nucleus Accumbens; Opiate Addiction; Opioid; Outcome; Pain; Pain Research; Patients; Pharmaceutical Preparations; Phase; Principal Investigator; Process; Psychology; Request for Proposals; Research; Research Project Grants; Research Training; Rewards; Risk; Spinal Cord; Symptoms; System; Testing; Time; Training; Training Programs; Universities; Woman; base; brain dysfunction; career; central sensitization; chronic pain; cohort; fibromyalgia pain; fibromyalgia patients; financial incentive; human imaging; ineffective therapies; neuroimaging; opioid therapy; pain processing; pain symptom; patient population; prescription opioid; public health relevance; research study; response; responsible research conduct; reward anticipation; statistics

 DESCRIPTION (provided by applicant): Although opioids are widely prescribed for chronic pain due to fibromyalgia (FM), the effects of opioid medications on the activity of the central nervous system (CNS) and on reward behavior and clinical outcomes have not been determined for this indication. Current evidence strongly suggests that altered activity in the brain and spinal cord contributes to the chronicity of FM symptoms, and opioids are known to produce similar changes in CNS activity. Thus, the central hypothesis is that opioids exacerbate existing alterations in pain and reward processes in the CNS in individuals with FM. To test this hypothesis, the proposal includes clinical neuroimaging research projects and a comprehensive training plan that Dr. Katherine Martucci, Ph.D., will conduct under the guidance of expert mentors, advisors and collaborators at Stanford University (Drs. Sean Mackey, Brian Knutson, Jodie Trafton, and Gary Glover). During the K99 mentored training phase (Years 1-2; Aims 1 & 2), Dr. Martucci will conduct a clinical research study using brain and spinal cord functional magnetic resonance imaging (fMRI) to measure differences between individuals with FM who take opioids and individuals with FM who do not. Aim 1 will determine the effect of opioids on levels of pain and spinal cord activity in FM. Aim 2 will determine the effect of opioids on the brain's reward systems and reward behavior in FM. This phase will include a training program in advanced CNS neuroimaging analysis, brain reward processes, opioid therapy, clinical research, advanced statistics, and responsible research conduct. It will also include training in lab management, mentoring, and teaching through didactic courses at Stanford University and from established mentors. During the R00 independent research phase (Years 3-5; Aim 3), Dr. Martucci will conduct a longitudinal clinical study of individuals with FM, both opioid-dependent and opioid-naïve, to determine changes in pain, symptoms, and CNS activity in FM over time. The projects and training of the initial mentored K99 training phase will effectively prepare Dr. Martucci to conduct the projects proposed for the later independent R00 phase. Together, these projects will provide a more complete picture of the effects of opioid medications in FM and will fill the critical knowledge gaps of inherent risks of neurobiological changes and altered behavior and psychology that occur when prescribing opioids. This proposal requests support for Dr. Martucci to receive additional training in order to enhance and expand her current level of graduate and postdoctoral research expertise in neurobiology of pain processing and chronic pain research. This will enable her to successfully transition to an independent R01-funded, faculty- level principal investigator and to achieve her long-term goal of establishing an independent research lab focused on neurological and behavioral alterations in chronic pain.

 描述（由适用提供）：尽管阿片类药物是由于纤维肌痛（FM）引起的慢性疼痛的广泛规定，但尚未确定阿片类药物对中枢神经系统（CNS）（CNS）（CNS）活性的影响以及奖励行为和临床结果。当前的证据强烈表明，大脑和脊髓的活性改变会导致FM症状的慢性性，并且已知阿片类药物会在CNS活性中产生类似的变化。这就是中心假设是，阿片类药物加剧了FM患者中枢神经系统中疼痛和奖励过程的现有变化。为了检验这一假设，该提案包括临床神经影像学研究项目以及凯瑟琳·马图奇（Katherine Martucci）博士博士的全面培训计划，将在斯坦福大学（Stanford University）的专家导师，顾问和合作者的指导下进行（Sean Mackey博士，Brian Knutson，Jodie Trafton和Gary Glover）。在K99修复训练阶段（1-2年；目标1和2），Martucci博士将使用脑和脊髓功能磁共振成像（fMRI）进行临床研究，以衡量接受阿片类药物和没有FM的人的FM个人之间的差异。 AIM 1将确定阿片类药物对FM疼痛和脊髓活性水平的影响。 AIM 2将确定卵形对大脑奖励系统的影响和FM中的奖励行为。此阶段将包括高级中枢神经系统神经成像分析，大脑奖励过程，卵巢疗法，临床研究，高级统计和负责任的研究行为的培训计划。它还将包括通过斯坦福大学的教学课程和成熟的导师进行实验室管理，心理和教学的培训。在R00独立研究阶段（3-5年； AIM 3），Martucci博士将对FM（阿片类药物依赖性和阿片类药物）的个体进行纵向临床研究，以确定随着时间的推移，FM的疼痛，症状和CNS活性的变化。最初修复K99培训阶段的项目和培训将有效地准备Martucci博士，以进行后来的独立R00阶段提议的项目。这些项目将共同提供FM中阿片类药物的影响的更完整的描述，并填补在开处阿片类药物时发生神经生物学变化风险以及改变行为和心理学风险的关键知识差距。该建议要求支持Martucci博士接受额外的培训，以增强和扩大她目前在疼痛处理和慢性疼痛研究神经生物学方面的研究生和博士后研究专业知识。这将使她能够成功地过渡到由R01资助的独立教师级的首席研究员，并实现了她的长期目标，即建立一个专注于慢性疼痛的神经系统和行为改变的独立研究实验室。