Center for chronic pain and drug abuse

慢性疼痛和药物滥用中心

基本信息

批准号：
10440289
负责人：
Apkar Vania Apkarian
金额：
$ 166.72万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10440289
关键词：
Absence of pain sensation Achievement Address Adult Affect American Analgesics Anatomy Animal Model Animals Behavior Behavioral Biological Biological Markers Brain Brain imaging Brain region Cells Clinical Cognitive Communities Development Diabetes Mellitus Disease Dopamine Dopamine D2 Receptor Dorsal Dose Drug Addiction Drug abuse Electrophysiology (science)Elements Emotional Epidemic Episodic memory Exposure to Funding Genes Genetic Goals Heart Diseases Hippocampus (Brain)Human Individual Injury International Knowledge Link Maintenance Malignant Neoplasms Medial Medical Memory Mission Modeling Molecular Molecular Target Morphine Motivation Motor Mus Neurons Opiate Addiction Opioid Opioid Analgesics Patients Peripheral Pilot Projects Placebos Procedures Productivity Property Psychological reinforcement Rattus Relapse Research Research Personnel Research Support Risk Rodent Rodent Model Role Science Scientist Self Administration Shapes Source Synapses Techniques Testing Universities Work addiction base brain circuitry chronic back pain chronic pain chronic pain management chronic pain patient clinically relevant cohort computerized data processing conditioned place preference cost data sharing data tools disability experimental study human imaging imaging approach imaging study insight mesolimbic system morphine administration novel opioid abuse opioid epidemic opioid exposure opioid use disorder opioid withdrawal overdose death pain behavior pain chronification prescription opioid programs sex statistics therapeutic target tool transcriptomics virtual

项目摘要

Abstract Overall, Center for Chronic Pain and Drug Abuse: This is a resubmission of a P50 application, PAR-16-009, to launch a Center for Chronic Pain and Drug Abuse. Our Center proposal is built on the recognition that opioid addiction and chronic pain engage the same brain circuitry, the mesolimbic system. Although opiates continue to be prescribed to millions of chronic pain patients, and chronic pain is a primary contributor to the ongoing opiate epidemic, there is virtually no scientific knowledge regarding mechanisms that control the interaction between chronic pain and opioid exposure. Our Center is organized to uncover mechanisms that causally control this interaction, and to aggressively search for critical molecules, circuits, and biomarkers, and ultimately, novel non-addictive treatment options for chronic pain. Our overarching hypothesis is that the chronic pain state primes limbic circuitry for opiate abuse, and also, that associated adaptations depend on the duration and dose of both chronic pain and opioid exposure. The hypothesis will be rigorously tested using an array of cutting-edge tools, to study the underlying mechanisms from the scale of genes to molecules, circuits and whole-brain anatomy and function. Patients with chronic back pain (CBP) are the largest and best characterized group of humans at risk for opioid abuse disorder. Project 1 will use advanced brain imaging approaches to study brain properties in CBP, and in a rat model of chronic pain (SNI), for opioid exposure. The human studies will be 1) cross-sectional, comparing brain anatomy and function between groups; and 2) within-subject, examining brain activity and network properties during brief opioid withdrawal and re-exposure to placebo, opioid, or dopamine. The study seeks to identify: biomarkers for opioid use disorder (OUD); brain distortions and cognitive, emotional, and motor changes associated with opioid exposure; and the role of dopaminergic circuitry in OUD and opioid analgesia. Parallel brain imaging in rats with chronic pain (SNI) and with morphine exposure (MSA or MCPP) will establish cross-species correspondences, and interrogate circuitry studied in Projects 2-4. Project 2 will focus on circuits involved in motivation and addiction (mPFC, NAc, VTA); Project 3 will focus on episodic memory and relapse for opiate seeking (dorsal hippocampus, dH, interaction with VTA and cortex); Project 4 will focus on genetically defined single-cell adaptations for the mesolimbic region underlying opioid reinforcement (VTA and its connectivity to NAc and dH), searching for novel molecular targets to control chronic pain. All animal studies will use the same model for chronic pain. Projects 2-4 use genetically modified mice; Projects 2, 3 use opto- and chemo- genetics, and electrophysiology; and Project 4 uses single cell transcriptomics. The rodent behavior core will generate SNI rodents with MSA or MCPP for all projects. The computational and statistics core will provide data processing support, and enable data sharing with the research community at large. The administrative core will oversee the organizational, and educational missions of the program, including the pilot projects element, which will fund small projects from junior scientists to accelerate the Center’s science. 1

摘要总体，慢性疼痛和药物滥用中心：这是PAR-16-009的P50申请的重新提交，用于启动慢性疼痛和毒品中心虐待。我们的中心提议建立在阿片类药物成瘾和慢性疼痛相同的认识的基础上脑电路，中唇系统。尽管优化继续为数百万慢性疼痛开处方患者，慢性疼痛是持续优化流行病的主要因素，几乎没有科学有关控制慢性疼痛与阿片类药物暴露之间相互作用的机制的知识。我们的中心的组织以发现随便控制这种相互作用的机制，并积极寻找关键分子，电路和生物标志物，最终是慢性的新型非添加治疗选择疼痛。我们的总体假设是用于优化的慢性疼痛状态边缘电路滥用以及相关的适应性取决于慢性疼痛和阿片类药物的持续时间和剂量接触。该假设将使用一系列尖端工具进行严格检验，以研究基础从基因到分子，电路和全脑解剖结构和功能的机制。患者慢性背痛（CBP）是面临阿片类药物滥用障碍风险的最大，最佳的人群。项目1将使用先进的脑成像方法研究CBP中的大脑特性，并在大鼠模型中慢性疼痛（SNI），用于阿片类药物。人类研究将为1）横截面，比较脑解剖结构组之间的功能； 2）主题内检查大脑活动和网络特性简短的阿片类药物提取并重新暴露于安慰剂，阿片类药物或多巴胺。该研究旨在识别：生物标志物用于阿片类药物使用障碍（OUD）；大脑扭曲和认知，情感和运动变化卵子类药物暴露；以及多巴胺能回路在OUD和卵巢镇痛中的作用。平行大脑成像患有慢性疼痛（SNI）和吗啡暴露（MSA或MCPP）的大鼠将建立跨物种对应关系，并在项目2-4中研究的电路。项目2将重点放在涉及的电路上动机和成瘾（MPFC，NAC，VTA）；项目3将重点关注情节记忆和继电器以进行优化寻求（背侧海马，DH，与VTA和皮质的相互作用）；项目4将专注于一般定义阿片类药物增强基础的中左右区域的单细胞适应（VTA及其连接到 NAC和DH），寻找新的分子靶标，以控制慢性疼痛。所有动物研究都将使用相同的慢性疼痛的模型。项目2-4使用一般修改的小鼠；项目2、3使用opt-和化学疗法遗传学和电生理学；项目4使用单细胞转录组学。啮齿动物行为核心将使用MSA或MCPP生成SNI啮齿动物。计算和统计核心将提供数据处理支持，并启用与整个研究社区的数据共享。行政核心将监督该计划的组织和教育任务，包括试点项目元素，将资助从初级科学家的小型项目，以加速该中心的科学。 1

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Psychosocial, Functional, and Emotional Correlates of Long-Term Opioid Use in Patients with Chronic Back Pain: A Cross-Sectional Case-Control Study.

DOI：
10.1007/s40122-021-00257-w
发表时间：
2021-06
期刊：
Pain and therapy
影响因子：
4
作者：
Wakaizumi K;Vigotsky AD;Jabakhanji R;Abdallah M;Barroso J;Schnitzer TJ;Apkarian AV;Baliki MN
通讯作者：
Baliki MN

On the Relationship Between Pain Variability and Relief in Randomized Clinical Trials.

DOI：
10.3389/fpain.2022.844309
发表时间：
2022
期刊：
Frontiers in pain research (Lausanne, Switzerland)
影响因子：
0
作者：
通讯作者：

Adaptive alterations in the mesoaccumbal network after peripheral nerve injury.

DOI：
10.1097/j.pain.0000000000002092
发表时间：
2021-03-01
期刊：
Pain
影响因子：
7.4
作者：
通讯作者：

GuPPy, a Python toolbox for the analysis of fiber photometry data.

DOI：
10.1038/s41598-021-03626-9
发表时间：
2021-12-20
期刊：
Scientific reports
影响因子：
4.6
作者：
Sherathiya VN;Schaid MD;Seiler JL;Lopez GC;Lerner TN
通讯作者：
Lerner TN

Validating a biosignature-predicting placebo pill response in chronic pain in the settings of a randomized controlled trial.

DOI：
10.1097/j.pain.0000000000002450
发表时间：
2022-05-01
期刊：
Pain
影响因子：
7.4
作者：
Vachon-Presseau E;Abdullah TB;Berger SE;Huang L;Griffith JW;Schnitzer TJ;Apkarian AV
通讯作者：
Apkarian AV