Human Brain Functional and Structural Interactions Between Chronic Pain and Opioi

该P20中心研究计划的项目1将侧重于人类受试者，以检查 慢性疼痛和阿片类药物成瘾的功能和结构电路改变。它将专门研究 用于测试/再测试目的的两个单独的受试者群组，每个群组包括五组人类受试者， 受试者代表阿片类药物成瘾和慢性疼痛之间的连续体。这五个小组将 包括：（i）没有慢性疼痛史的阿片类药物成瘾者，（ii） 对阿片类镇痛药产生成瘾行为的慢性疼痛患者，（iii）慢性疼痛患者 疼痛的人有基于治疗的接触止痛药，但没有成瘾行为，和（iv）个人与 没有接触过止痛药的慢性疼痛患者。第五组健康对照（v）， 疼痛或对阿片类镇痛剂成瘾将作为四个临床组的基线对照组（i）- （iv）。在两个队列的这些受试者组中，我们将比较和对比BOLD信号 通过功能性磁共振成像在一组有限的奖励/厌恶大脑区域中测量，这些区域与 成瘾和慢性疼痛，如杏仁核/海马，腹侧 被盖和前额皮质区域。神经功能将根据形态测量和 五组人类受试者的拓扑测量。我们假设阿片类药物成瘾和 慢性疼痛将调节奖励/厌恶行为和先天区域的功能， 并共享与改变的形态测量相关的表型特征。在三个具体目标中， 我们将测试在四个临床组中，轻微的奖励或厌恶刺激是否会引起减弱的反应。 成瘾和/或慢性疼痛，以及强烈厌恶的刺激是否引起过敏反应。目的 1将使用按键范例测试判断和决策来评估奖励处理的差异 对药物线索的相对偏好或成瘾的表型特征。目标2将进行比较， 使用热疼痛和货币对比五个人类群体的身体和心理厌恶 在一场机会游戏中的损失。目标3将确定成瘾中的大脑结构/拓扑改变是否 也发现在慢性疼痛，并评估结构/拓扑差异与症状的相互作用 与目标1和2的严重程度和功能差异。

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.