Human Brain Functional and Structural Interactions Between Chronic Pain and Opioi

慢性疼痛与阿片类药物之间的人脑功能和结构相互作用

• 批准号: 7608892
• 负责人: HANS C BREITER
• 金额: $ 33.56万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608892
• 关键词: Acute; Addictive Behavior; Amygdaloid structure; Analgesics; Anatomy; Animals; Attenuated; Aversive Stimulus; Back; Behavior; Brain; Brain region; Categories; Chronic; Clinical; Condition; Control Groups; Cues; Diagnosis; Disease; Event; Experimental Designs; Experimental Psychology; Exposure to; Functional Magnetic Resonance Imaging; Hippocampus (Brain); Human; Illicit Drugs; Image; Individual; Judgment; Measures; Medial; Medicine; Modeling; Molecular; Negative Finding; Neurophysiology - biologic function; Neurosciences; Non-Malignant; Nucleus Accumbens; Opiate Addiction; Opiates; Opioid; Opioid Analgesics; Organism; Outcome Measure; Outcomes Research; Pain; Pain management; Patients; Pharmaceutical Preparations; Phenotype; Prefrontal Cortex; Process; Purpose; Recording of previous events; Relative (related person); Research; Rewards; Rodent; Rodent Model; Sensory; Severities; Signal Transduction; Structure; Substantia nigra structure; Symptoms; Testing; Ventral Tegmental Area; addiction; attenuation; base; chronic pain; clinical application; cohort; desire; human subject; interest; morphometry; neuroimaging; pre-clinical; preclinical study; preference; prescription document; prescription procedure; psychologic; relating to nervous system; research clinical testing; research study; response; reward processing

Project 1 of this P20 center research plan will focus on human subjects to examine the interaction of functional and structural circuitry alterations in chronic pain and opioid addiction. It will specifically examine two separate cohorts of subjects for test/retest purposes, each cohort comprising five groups of human subjects who represent a continuum between opioid addiction and chronic pain. These five groups will include: (i) individuals with addiction to opiates who have no history of chronic pain, (ii) individuals with chronic pain who have developed addictive behaviors toward opioid analgesics, (iii) individuals with chronic pain who have treatment based exposure to analgesics but no addiction behavior, and (iv) individuals with chronic pain who have no exposure to analgesics. A fifth group of healthy controls (v) with neither chronic pain nor addiction to opioid analgesics will serve as a baseline control group for the four clinical groups (i) - (iv). Across these groups of subjects in each of the two cohorts, we will compare and contrast BOLD signal measured by functional MRI in a limited set of reward/aversion brain regions that have been implicated in both addiction and chronic pain, such as the nucleus accumbens, amygdala/hippocampus, ventral tegmentum, and regions of the prefrontal cortex. Neural function will be assessed against morphometric and topological measures across the five groups of human subjects. We hypothesize that opioid addiction and chronic pain will modulate reward/aversion behavior and function in apriori regions in a convergent direction and share phenotypic features, correlating with altered morphometry measures. Across three specific aims, we will test if mildly rewarding or aversive stimuli elicit attenuated responses across the four clinical groups with addiction and/or chronic pain, and whether strongly aversive stimuli elicit hypersensitive responses. Aim 1 will assess differences in reward processing using a keypress paradigm testing judgment and decisionmaking around relative preference for drug cues or phenotypic features of addiction. Aim 2 will compare and contrast physical and psychological aversion across the five human groups using thermal pain and monetary losses in a game of chance. Aim 3 will determine if brain structural/topological alterations in addiction are also found in chronic pain, and assess the interactions of structural/topological differences with symptom severity and functional differences from Aims 1 and 2.

该P20中心研究计划的项目1将侧重于人类受试者，以检查 慢性疼痛和阿片类成瘾的功能和结构回路改变。它将专门检查 两个单独的人群用于测试/重新测试目的，每个人群包括五组人 代表阿片类药物成瘾和慢性疼痛之间连续体的受试者。这五组将 包括：（i）对没有慢性疼痛史的阿片类药物成瘾的人，（ii） 慢性疼痛对阿片类镇痛药产生了上瘾的行为，（iii）患有慢性的人 疼痛的疼痛患有基于治疗的镇痛药但没有成瘾行为，并且（iv）患有 没有暴露于镇痛药的慢性疼痛。没有慢性的第五组健康对照（V） 对阿片类镇痛药的痛苦或成瘾将作为四个临床组（i） - （iv）。在这两个队列中的每个主题中，我们将比较和对比粗体信号 通过功能性MRI在有限的奖励/厌恶大脑区域中测量 成瘾和慢性疼痛，例如伏隔核，杏仁核/海马，腹侧 tementum和前额叶皮层的区域。神经功能将根据形态计量计而评估 五组人类受试者的拓扑度量。我们假设阿片类药物成瘾和 慢性疼痛将调节奖励/厌恶行为和在收敛方向上的APRIORI区域 并共享表型特征，与变化的形态计量指标相关。在三个特定目标中 我们将测试四个临床组的轻度奖励或厌恶刺激会引起减弱的反应 成瘾和/或慢性疼痛，以及强烈厌恶刺激是否引起过度反应。目的 1将使用按键范式测试判断和决策评估奖励处理的差异 围绕对药物提示或成瘾的表型特征的相对偏爱。 AIM 2将比较和 使用热痛和金钱的对比五个人类的身体和心理厌恶 机会游戏中的损失。 AIM 3将确定成瘾中的大脑结构/拓扑改变是否是 还发现了慢性疼痛，并评估结构/拓扑差异与症状的相互作用 目的1和2的严重性和功能差异。