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: 10038789
• 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/10038789
• 关键词: Absence of pain sensation; Affect; Afghanistan; Area; Behavioral; Biological Markers; Brain; Brain Injuries; Brain Stem; Classification; Clinical; Community Integration; Conflict (Psychology); Control Groups; Data; 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; comorbidity; conditioned pain modulation; detection method; effective therapy; endogenous opioids; hemodynamics; imaging modality; imaging platform; imaging system; improved; mild traumatic brain injury; military veteran; 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TBI（mTBI）。