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: 9736938
• 负责人: Katherine Theresa Martucci
• 金额: $ 24.9万
• 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/9736938
• 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; 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（由申请人提供）：虽然阿片类药物被广泛用于治疗纤维肌痛 (FM) 引起的慢性疼痛，但阿片类药物对中枢神经系统 (CNS) 活动、奖赏行为和临床结果的影响尚未确定。目前的证据强烈表明，大脑和脊髓活动的改变会导致 FM 症状的慢性化，而阿片类药物已知会导致中枢神经系统活动发生类似的变化，因此，核心假设是阿片类药物会加剧现有的 FM 症状。为了检验这一假设，该提案包括临床神经影像研究项目和 Katherine Martucci 博士将在专家导师、顾问的指导下进行的综合培训计划。以及斯坦福大学的合作者（Sean Mackey 博士、Brian Knutson、Jodie Trafton 和 Gary Glover）在 K99 指导培训阶段（第 1-2 年；目标 1 和 2）， Martucci 博士将使用大脑和脊髓功能磁共振成像 (fMRI) 进行一项临床研究，以测量服用阿片类药物的 FM 个体和不服用阿片类药物的 FM 个体之间的差异，目标 1 将确定阿片类药物对 FM 水平的影响。目标 2 将确定 FM 中阿片类药物对大脑奖励系统和奖励行为的影响。该阶段将包括高级 CNS 神经影像分析、大脑奖励过程、阿片类药物治疗、临床的培训计划。它还将包括实验室管理培训、指导以及通过斯坦福大学和知名导师进行的教学培训。在 R00 独立研究阶段（第 3-5 年；目标 3）， Martucci 博士将对 FM 患者（包括阿片类药物依赖者和未使用过阿片类药物的患者）进行纵向临床研究，以确定 FM 患者的疼痛、症状和中枢神经系统活动随时间的变化。 最初指导的 K99 项目和培训。培训阶段将有效地为 Martucci 博士开展为后续独立 R00 阶段提出的项目做好准备，这些项目将共同提供阿片类药物对 FM 的影响的更完整的了解，并将填补神经生物学固有风险的关键知识空白。该提案要求支持 Martucci 博士接受额外的培训，以提高和扩大她目前在疼痛处理和慢性疼痛研究的神经生物学方面的研究生和博士后研究专业知识。使她能够成功转型为独立的 R01 资助的教职级首席研究员，并实现了建立一个专注于慢性疼痛的神经和行为改变的独立研究实验室的长期目标。