Sleep disturbance as a putative mechanism for reward system dysfunction

描述（由申请人提供）：该指导以患者为导向的研究职业发展奖（K23）提案包括协调的培训计划和研究项目，将促进候选人向独立研究者的过渡。它将为候选人提供工具，使其成为睡眠障碍和奖励系统功能关联背后的基础人类行为科学的领先专家，并开发关于睡眠障碍，奖励系统和阿片类药物依赖患者慢性疼痛相互关系的基础和临床研究的独立计划。该主题领域很重要，因为阿片类药物依赖是一个日益严重的公共卫生问题，睡眠障碍和慢性疼痛越来越被认为是普遍存在且有问题的合并症，了解睡眠障碍如何改变奖励系统功能的行为和情感指标可能会增强有限的治疗选择阿片类药物依赖慢性疼痛患者。从长远来看，候选人的研究计划将采用多模式评估策略，包括人类生物行为实验室实验和纵向临床研究。候选人需要精通睡眠和奖励系统的病理生理学和神经生物学基础。具体的短期培训目标是：1）获得实验睡眠方法和睡眠障碍评估的专业知识; 2）获得神经生物学和奖励系统评估的培训; 3）获得阿片类药物依赖患者研究的培训; 4）获得负责任的研究行为的培训。建议的短期发展活动将使候选人能够通过提供必要的技能来实现其长期目标，以a）安全有效地操纵睡眠; B）客观地测量睡眠心理生理学; c）客观地测量行为奖励系统功能d）从生物行为的角度自信地解释功能性奖励系统变化的证据; e）招募，保留和负责任地执行阿片类药物依赖患者的研究方案;和f）了解阿片类药物成瘾的心理药理学基础和共病慢性疼痛的临床细微差别。该研究项目分为两个研究。研究一将在健康受试者的睡眠剥夺实验中建立睡眠障碍诱导的奖励系统功能障碍的基本行为模型。研究2将收集横断面试点数据，以确定睡眠障碍与奖励系统功能障碍的关联是否在有慢性疼痛的阿片类药物依赖患者中更大。协调的培训和研究计划从逻辑上扩展了候选人先前在慢性肌肉骨骼疼痛中的情绪调节方面的工作，并形成了一个新的研究方向，该方向解决了我们目前对睡眠障碍如何影响奖励系统功能的理解中的差距，以及该途径如何有助于阿片类药物依赖患者的慢性疼痛。

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award (K23) proposal includes a coordinated training plan and research project that will facilitate the Candidate's transition to independent investigator. It will provide the Candidate with the tools to become a leading expert on the basic human behavioral science behind the association of sleep disturbance and reward system function, and to develop an independent program of basic and clinical research on the interrelations of sleep disturbance, the reward system, and chronic pain in opioid-dependent patients. This topic area is important because opioid dependence is a growing public health problem, sleep disturbance and chronic pain are increasingly recognized as prevalent and problematic comorbidities, and understanding how sleep disturbance alters behavioral and affective measures of reward system function may enhance the limited treatment options for opioid-dependent patients with chronic pain. Long-term, the Candidate's program of research will employ a multimodal assessment strategy involving human biobehavioral laboratory experiments and longitudinal clinical research. The Candidate will need to become well-versed in the pathophysiological and neurobiological underpinnings of sleep and the reward system. Specific short-term training goals are: 1) Gain expertise in experimental sleep methods and assessment of sleep disturbance; 2) Gain training in the neurobiology and assessment of the reward system; 3) Gain training in research with opioid-dependent patients and 4) Gain training in the responsible conduct of research. The proposed short-term development activities will enable the Candidate to achieve his long-term goals by providing the necessary skill set to a) safely and effectively manipulate sleep; b) objectively measure sleep psychophysiology; c) objectively measure behavioral reward system function d) confidently interpret evidence of functional reward system changes from a biobehavioral perspective; e) recruit, retain, and responsibly execute research protocols with opioid dependent patients; and f) understand the psychopharmacological basis of opioid addiction and the clinical nuances of comorbid chronic pain. The proposed research project is divided into 2 studies. Study 1 will establish a basic behavioral model of sleep disturbance-induced reward system dysfunction in a within-person sleep deprivation experiment with healthy subjects. Study 2 will gather cross-sectional pilot data to determine if the association of sleep disturbance with reward system dysfunction is greater in opioid-dependent patients with versus without chronic pain. The coordinated training and research plans logically extend from the Candidate's prior work on emotion regulation in chronic musculoskeletal pain, and forge a novel research direction that addresses gaps in our current understanding of how sleep disturbance affects reward system function, and how that pathway contributes to chronic pain in patients with opioid dependence.