Opioid Abuse and Chronic Pain: An fMRI Model of Negative Reinforcement

描述（由申请人提供）：在过去的十年中，慢性疼痛患者使用阿片类镇痛药的数量大幅增加。然而，滥用处方类阿片镇痛药是一个日益严重的公共卫生问题，类阿片药物已超过可卡因和海洛因，成为滥用的主要药物。慢性疼痛是另一个重要的公共卫生问题，影响着5000多万美国人，每年在医疗保健费用、残疾、工资损失和生产力方面造成700多亿美元的损失。慢性疼痛患者阿片类药物滥用的发生率和流行率尚不清楚，对慢性疼痛患者易发生阿片类药物滥用的因素知之甚少。对于与异常阿片类药物使用行为发展相关的行为偶然性，我们所知的就更少了，但一些基本的操作性条件反射过程可能涉及其中。具体来说，负强化原则可能会影响慢性疼痛患者的早期阿片类药物使用行为，潜在地增加阿片类药物滥用的可能性。疼痛本质上是一种令人厌恶的刺激，而慢性疼痛患者的这种厌恶刺激即使不是一直存在，也是大多数时候存在的。处方阿片类药物（尤其是短效制剂）提供快速但暂时的减少或消除厌恶刺激，因此药物服用行为被消极地强化。一部分慢性疼痛患者了解到，服用比处方更多的阿片类药物，或服用比处方更频繁的阿片类药物，会导致更长时间的疼痛缓解和/或更大程度的疼痛减轻。关于这种缓解疼痛的回避学习行为的基本神经机制的信息很少。尽管最近神经成像技术和基于fmri的人类学习模型的发展取得了进展，但很少有模型可以用于研究扫描环境中的负强化。鉴于慢性疼痛在美国的普遍问题，越来越多的处方阿片类药物用于治疗慢性疼痛，以及阿片类药物滥用的问题日益严重，需要可靠和有效的模型来开始阐明慢性疼痛背景下参与负强化的神经过程。研究人员建议进一步开发和测试一种独特的人类疼痛负强化模型，以确定与疼痛回避行为负强化相关的关键大脑区域。来自3个队列的参与者（健康成人、有慢性疼痛和阿片类药物滥用/依赖史的患者、接受阿片类药物治疗的慢性疼痛患者和没有阿片类药物滥用/依赖史的患者）将接受功能磁共振成像（fMRI），在此期间，他们将接受块状强直性热疼痛刺激。他们的任务是学习一种行为来关闭热痛（负强化学习）。在疼痛的背景下，与负强化学习的不同方面相关的大脑区域将被检查。这项研究的发现可能有助于早期识别可能存在阿片类药物滥用风险的患者，并可能导致开发针对阿片类药物处方滥用的新干预措施。

DESCRIPTION (provided by applicant): Over the past decade there has been a substantial expansion of opioid analgesic use for patients who have chronic pain. The misuse of prescription opioid analgesics, however, is a growing public health problem and opioid medications have surpassed cocaine and heroin as the leading drugs of abuse. Chronic pain is another important public health problem that affects over 50 million Americans and costs over $70 billion per year in health care expenses, disability, lost wages and productivity. The incidence and prevalence of opioid misuse in patients treated for chronic pain is unclear and little is known about the factors predisposing chronic pain patients to opioid misuse. Even less is known about behavioral contingencies associated with the development of aberrant opioid-use behaviors, but some basic operant conditioning processes are likely to be involved. Specifically, negative reinforcement principles may shape early opioid-use behaviors in patients with chronic pain, potentially increasing the likelihood of opioid misuse. Pain is an intrinsically aversive stimulus, and in patients with chronic pain this aversive stimulus is present most, if not all of the time. Prescription opioid medications (especially shorter acting preparations) provide for a quick but temporary reduction or elimination of the aversive stimulus and thus medication-taking behaviors are negatively reinforced. A subset of chronic pain patients learn that taking more opioid medication than prescribed, or taking them more frequently than prescribed, results in longer periods of pain relief and/or greater pain reduction. There is very little information available regarding basic neural mechanisms involved in this avoidance-learning of pain-relieving behaviors. Despite recent advances in neuroimaging technologies and development of fMRI-based human learning models, few if any models for studying negative reinforcement in the scanning environment are available. Given the widespread problem of chronic pain in the United States, increasing use of prescription opioids for the treatment of chronic pain, and the rising problem of opioid misuse, reliable and valid models are needed to begin elucidating neural processes involved in negative reinforcement in the context of chronic pain. The Investigators propose to further develop and test a unique human model of negative reinforcement in the context of pain to identify key brain areas associated with negative reinforcement of pain-avoidance behaviors. Participants from 3 cohorts (healthy adults, patients with chronic pain and a history of opioid abuse/dependence, and patients with chronic pain on opioid therapy and no history of opioid abuse/dependence) will undergo an fMRI session during which they will receive blocks of tonic, thermal pain stimuli. They will be tasked with learning a behavior to turn-off the thermal pain (negative reinforcement learning). Brain areas associated with different aspects of negative reinforcement learning in the context of pain will be examined. Findings from this study could help in the early identification of patients that might be at risk for opioid misuse, and could lead to the development of new interventions for opioid prescription misuse. PUBLIC HEALTH RELEVANCE: Prescription opioid misuse has increased dramatically over the past decade and opioid medications have surpassed cocaine and heroin as the leading drugs of abuse. Little is known about the factors predisposing chronic pain patients to opioid misuse in the outpatient setting. Negative reinforcement principles may shape early opioid-use behaviors in patients with chronic pain potentially increasing the likelihood of opioid misuse, abuse and addiction. We propose to develop and test a unique, human model of negative reinforcement in the context of pain avoidance, and subsequently use that model to explore the neural mechanisms of addiction to pain medication.