Brain reorganization in chronic back pain and opioid exposure

慢性背痛和阿片类药物暴露的大脑重组

• 批准号: 10198885
• 负责人: Apkar Vania Apkarian
• 金额: $ 59.07万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198885
• 关键词: Absence of pain sensation; Analgesics; Anatomy; Animals; Biological Markers; Brain; Brain imaging; Brain scan; Cells; Characteristics; Clinical; Clinical Management; Clinical Trials; Cognitive; Consumption; Crossover Design; Data; Data Analyses; Dependence; Development; Dose; Double-Blind Method; Drug abuse; Emotional; Enrollment; Ensure; Exposure to; Female; Functional Magnetic Resonance Imaging; Genetic study; Human; Hyperalgesia; In Vitro; Individual; Knowledge; Link; Measures; Modeling; Molecular Genetics; Morphine; Motor; Mus; Naproxen; Non-Steroidal Anti-Inflammatory Agents; Opiate Addiction; Opioid; Opioid Analgesics; Outcome; Pain; Participant; Patients; Pharmaceutical Preparations; Phase; Physiological; Placebos; Population; Positron-Emission Tomography; Procedures; Process; Property; Psychological Dependence; Randomized; Rattus; Reporting; Research; Rest; Risk; Risk Factors; Rodent; Scanning; Self Administration; Series; Services; Signs and Symptoms; Sinemet; Study Subject; System; Testing; Time; Translating; United States National Institutes of Health; Validation; Viral; Visit; Vulnerable Populations; Withdrawal; addiction; behavioral response; blind; cell type; chronic back pain; chronic pain; chronic pain management; chronic painful condition; clinical application; conditioned place preference; craving; drug craving; drug withdrawal; experimental group; fluorodeoxyglucose positron emission tomography; human data; human subject; imaging study; in vivo; nerve injury; neural correlate; novel; opioid abuse; opioid epidemic; opioid exposure; opioid therapy; opioid use; opioid use disorder; opioid withdrawal; psychologic; sex; spared nerve; virtual

Abstract: Project 1, Adaptations of the brain in chronic pain with opioid exposure The current opioid epidemic is intimately linked with the clinical management of chronic pain. 15-20% of the US population suffers from the condition, and a sizable proportion of such patients are managed with opioids. Chronic back pain (CBP) is the most common chronic pain condition in the US. Research in the Apkarian lab has shown that brain addiction circuitry (mesocorticolimbic system), critical in opioid use disorder (OUD), is also causally linked to the development of chronic pain. Thus, an overarching hypothesis of this Project, and of our Center, is that opioid abuse liability and the development of chronic pain are interacting brain processes, and critical to explaining clinical outcomes of abuse liability and the loss/moderation of analgesic efficacy. Yet, there is virtually no human or rodent brain imaging evidence on the topic, and physiologic knowledge regarding the interaction between chronic pain, opioid analgesia and abuse liability is minimal. In this project, we will study brain reorganization and behavioral responses in chronic pain with opioid exposure, both in CBP and in a rat model of chronic pain (SNI). Aim 1a will study four groups: i) individuals with CBP managed with opioids and no signs of misuse (n=80); ii) patients with CBP and mild to moderate OUD (mOUD, n=80); iii) patients with CBP managed without opioids (n=25); and iv) healthy controls (n=25). We will track daily analgesic drug consumption and pain and craving reports over 1-2 weeks. In a single scan session, we collect brain anatomical and functional data (resting state fMRI, T1, DTI, ASL) to elucidate the neural correlates of pain, analgesia, and abuse liability. In Aim 1b, all participants from aim 1a will be assessed for motor, cognitive and emotional abilities (NIH Toolbox). Aim 1 results should distinguish between opioid resilient and vulnerable groups, and unravel the impact of opioid exposure on abilities and related brain maladaptations. In Aim 2a, 50% of the patients from groups i and ii (n=40/group) will be enrolled into a placebo-controlled drug withdrawal and re- exposure study. Opioid drug dispensing is delayed to provoke craving and/or increased pain, and participants are scanned during psychological withdrawal and after re-exposure. Re-exposure will involve their opioid drug, placebo, or sinemet and naproxen (DA+NSAID, a potential novel treatment), in a double-blind, randomized, cross-over design. Aim 2b will assess changes in motor, cognitive and emotional abilities at different phases of opioid withdrawal and re-exposure. Aim 2 data will differentiate circuitry for analgesia/hyperalgesia and OUD, test the effects of DA+NSAID on the brain, and the dependence of abilities on opioid states. Aim 3 will track brain activity and functional connectivity reorganization (rsfMRI and FDG PET), in SNI vs. sham rats, +/- morphine exposure. In some rats, brain imaging will be combined with viral chemogenetic manipulations to unravel circuit- and cell- type specific reorganization (for VTA, NAc, and dH). Aim 3 data will provide cross- species correspondences, linking human and rodent circuit adaptations, and establish in-vivo translational validity for the mouse in-vitro studies in Projects 2-4.

项目1：阿片类药物暴露下慢性疼痛的大脑适应性