Human Brain Functional and Structural Interactions Between Chronic Pain and Opioi

该P20中心研究计划的项目1将重点放在人类受试者身上，以考察 慢性疼痛和阿片成瘾的功能和结构回路改变。它将专门审查 用于测试/重新测试目的的两个单独的受试者队列，每个队列包括五组人类 代表阿片成瘾和慢性疼痛之间连续体的受试者。这五个小组将 包括：(1)没有慢性疼痛病史的鸦片成瘾者；(2)有 对阿片类镇痛剂产生成瘾行为的慢性疼痛患者，(Iii)慢性疼痛患者 接受过止痛药治疗但没有成瘾行为的人，以及(Iv)有 没有接触过镇痛剂的慢性疼痛。第五组健康对照(V)，既不是慢性 疼痛或阿片类止痛药成瘾将作为四个临床组的基线对照组(I)- (四)。在两个队列中的每一组中，我们将比较和对比粗体信号 通过功能磁共振在一组有限的奖赏/厌恶脑区进行测量，这些脑区与 成瘾和慢性疼痛，如伏隔核、杏仁核/海马体、腹侧 被盖，以及前额叶皮质的区域。神经功能将根据形态测量和 对五组人类受试者进行拓扑测量。我们假设阿片成瘾和 慢性疼痛将以趋同的方向调节先天区域的奖赏/厌恶行为和功能 有相同的表型特征，与改变的形态测量方法相关。在三个具体目标上， 我们将测试温和的奖赏或厌恶刺激是否会在四个临床组中引起减弱的反应 有毒瘾和/或慢性疼痛，以及强烈厌恶的刺激是否会引起过敏性反应。目标 1将使用按键范式测试、判断和决策来评估奖励处理的差异 围绕药物线索或成瘾的表型特征的相对偏好。目标2将比较和 使用热痛和金钱对比五组人的身体和心理厌恶 在一场碰运气的游戏中输掉。目标3将确定成瘾患者的大脑结构/拓扑变化是否 也在慢性疼痛中发现，并评估结构/拓扑差异与症状的相互作用 严重程度和功能与目标1和目标2的不同。

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.