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

描述(申请人提供)：在过去的十年里，阿片类止痛剂在慢性疼痛患者中的使用有了很大的扩展。然而，滥用处方阿片类止痛药是一个日益严重的公共卫生问题，阿片类药物已超过可卡因和海洛因成为主要的滥用药物。慢性疼痛是另一个影响5000多万美国人的重要公共卫生问题，每年在医疗费用、残疾、工资损失和生产力方面造成超过700亿美元的损失。阿片类药物滥用在治疗慢性疼痛患者中的发生率和流行率尚不清楚，对导致慢性疼痛患者滥用阿片类药物的因素也知之甚少。对于与异常阿片类药物使用行为的发展相关的行为偶然性更是知之甚少，但可能涉及一些基本的可操作性条件作用过程。具体地说，负强化原则可能会塑造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。疼痛是一种本质上令人厌恶的刺激，在慢性疼痛患者中，这种讨厌的刺激即使不是一直存在，也是最常见的。处方阿片类药物(特别是短效制剂)可以迅速但暂时地减少或消除令人厌恶的刺激，因此服药行为会得到负面强化。一组慢性疼痛患者了解到，服用比处方更多的阿片类药物，或者比处方更频繁地服用阿片类药物，会导致更长的疼痛缓解时间和/或更大的疼痛缓解。关于这种回避的基本神经机制--疼痛缓解行为的学习--可用的信息很少。尽管最近在神经成像技术和基于功能磁共振成像的人类学习模型方面取得了进展，但在扫描环境中研究负强化的模型即使有也很少。鉴于慢性疼痛在美国的普遍问题，处方阿片类药物用于治疗慢性疼痛的日益增多，以及阿片类药物滥用问题的日益严重，需要可靠和有效的模型来开始阐明在慢性疼痛的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在疼痛背景下负强化的独特人类模型，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(健康成年人、有阿片类药物滥用/依赖史的慢性疼痛患者，以及接受阿片类药物治疗但没有阿片类药物滥用/依赖史的慢性疼痛患者)将接受功能磁共振成像治疗，在此期间，他们将接受强效、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及早识别可能有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。 与公共卫生相关：处方阿片类药物滥用在过去十年中急剧增加，阿片类药物已超过可卡因和海洛因成为主要的滥用药物。对于导致慢性疼痛患者在门诊环境中滥用阿片类药物的因素，人们知之甚少。负强化原则可能会塑造慢性疼痛患者的早期阿片类药物使用行为，可能会增加阿片类药物滥用、滥用和成瘾的可能性。我们建议在疼痛避免的背景下开发和测试一个独特的人类负强化模型，并随后使用该模型来探索对止痛药上瘾的神经机制。

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.