Examination of mu opioid mediated pain vulnerability in combat mild Traumatic Brain Injury

轻度创伤性脑损伤中 mu 阿片类药物介导的疼痛脆弱性检查

• 批准号: 9564607
• 负责人: Irina A Strigo
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9564607
• 关键词: Absence of pain sensation; Affect; Afghanistan; Area; Behavioral; Biological Markers; Brain; Brain Injuries; Brain Stem; Classification; Clinical; Community Integration; Comorbidity; Conflict (Psychology); Control Groups; Data; Detection; Development; Diffusion Magnetic Resonance Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Hybrids; Imaging Device; Individual; Injury; Iraq; Lead; Link; Magnetic Resonance Imaging; Measures; Mediating; Midbrain structure; Molecular; Morbidity - disease rate; Neurotransmitters; Opioid; Outcome; Pain; Pain management; Pain quality; Pathway interactions; Personal Satisfaction; Pharmaceutical Preparations; Pharmacological Treatment; Physiological; Population; Positron-Emission Tomography; Predisposition; Prevention; Psychophysics; Public Health; Quality of life; Reporting; Research; Resistance; Rewards; Role; Severities; Signal Transduction; Source; Stress; Structure; System; Techniques; Testing; Therapeutic; Time; Trauma; Traumatic Brain Injury; Treatment Cost; United States; Veterans; Work; base; central pain; chronic pain; clinical pain; combat; conditioned pain modulation; effective therapy; endogenous opioids; hemodynamics; imaging modality; imaging platform; imaging system; improved; mild traumatic brain injury; mu opioid receptors; neuroimaging; neurotransmission; novel; opioid abuse; pain behavior; pain inhibition; prescription opioid; psychologic; psychological symptom; rehabilitative care; response; side effect; transmission process; white matter

Nearly 2 million people in the United States sustain traumatic brain injury(TBI) every year and mild TBI(mTBI) is considered a “signature injury” of those involved in Iraq and Afghanistan conflicts. Pain after such injury occurs in >50% of the time, worsens clinical course, interferes with community integration, and dramatically increases the costs of treatment. Despite pain being considered an important public health issue, the pathophysiology of pain in mTBI is currently unknown, which limits development of novel and effective treatments. The long-term goal of this research is to determine biological markers for the increased pain vulnerability after traumatic brain injury that can be used to improve chronic pain prevention and treatments in our Veterans. The immediate goals of this revised application are to examine the role of opioidergic transmission and circuitry in the increased pain vulnerability in Veterans who sustained mTBI during combat. Our central hypothesis is that brain Mu (μ)-opioid receptor (MOR) availability will show regional variability in Veterans with combat mTBI with and without chronic pain, with most decrease observed in the co-morbid pain and mTBI group. We will use novel hybrid Positron Emission Tomography and Magnetic Resonance Imaging (PET-MRI) platform that provides complementary and simultaneous information about the hemodynamic response and neurotransmitter activation and thus allows direct classification of function of the endogenous pain control in individuals who has pain and mTBI. This work will allow determination of behavioral, microstructural, functional and molecular integrity of the opioidergic circuitry and its relationship to clinical pain behaviors and quality of life. Guided by strong preliminary data the central hypothesis will be tested by pursuing two specific aims: 1) To examine the complementary impact of mTBI and chronic pain on the integrity of pain modulatory systems; 2) To distinguish the complementary impact of mTBI and chronic pain on the capability of pain modulatory systems. This work is significant since it will provide: 1) a mechanism for pain and enhanced pain vulnerability following mTBI; and 2) better imaging tool to detect pain after mTBI. Veterans are often prescribed opioids for pain. These drugs have a high potential for abuse and changes in the endogenous opioid system may contribute to alterations in the rewarding effects of these drugs; thus mTBI individuals may be particularly vulnerable to exogenous opioids. The current proposal fills an important gap in understanding how MOR mediated neurotransmission, the primary target of opioid medications, is affected in pain and mTBI. !

美国每年有近200万人遭受创伤性脑损伤(TBI)和轻度脑损伤(MTBI) 被认为是参与伊拉克和阿富汗冲突的人的“标志性伤害”。这种损伤后的疼痛 50%的时间发生在&gt；，恶化临床病程，干扰社区融合，并显著 增加了治疗成本。尽管疼痛被认为是一个重要的公共卫生问题，但 目前，mTBI中疼痛的病理生理学机制尚不清楚，这限制了新的和有效的开发。 治疗。这项研究的长期目标是确定疼痛增加的生物标志物 创伤性脑损伤后的脆弱性可用于改善慢性疼痛的预防和治疗 我们的退伍军人。这一修订后的应用的直接目标是检查阿片类药物的作用 在战斗中遭受mTBI的退伍军人中，痛觉易感性增加的传递和回路。 我们的中心假设是，脑内Mu(μ)-阿片受体(MOR)的可用性将在 患有和不伴有慢性疼痛的战斗mTBI的退伍军人，大多数减少在合并疼痛中观察到。 和mTBI组。我们将使用新型混合正电子发射断层扫描和磁共振成像 (PET-MRI)平台，提供有关血流动力学的补充和同步信息 反应和神经递质激活，从而允许直接对内源性 有疼痛和mTBI的个体的疼痛控制。这项工作将允许确定行为， 阿片能神经回路的微结构、功能和分子完整性及其与临床疼痛的关系 行为和生活质量。在强劲的初步数据的指导下，中心假设将得到以下检验 追求两个具体目标：1)研究mTBI和慢性疼痛对 疼痛调节系统的完整性；2)区分mTBI和慢性脑损伤的互补影响 疼痛对疼痛调节系统的能力。这项工作意义重大，因为它将提供：1) MTBI后疼痛的机制和增强的疼痛易感性；以及2)更好的检测疼痛的成像工具 在mTBI之后。退伍军人经常被开出止痛的阿片类药物。这些药物有很高的滥用潜力和 内源性阿片系统的变化可能有助于改变这些药物的奖赏效应； 因此，mTBI患者可能特别容易受到外源性阿片类药物的影响。当前的提案填补了 在理解MOR如何介导阿片类药物的主要靶点神经传递方面存在重要差距 药物，在疼痛和脑外伤中受到影响。 好了！