Sleep disturbance as a putative mechanism for reward system dysfunction

描述(由申请人提供)：这项以患者为导向的研究职业发展奖(K23)建议包括一个协调的培训计划和研究项目，将促进候选人向独立调查员的过渡。它将为候选人提供工具，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，并开发一个独立的基础和临床研究项目，研究阿片类药物依赖患者睡眠障碍、奖励系统和慢性疼痛的相互关系。这个主题领域很重要，因为阿片类药物依赖是一个日益严重的公共健康问题，睡眠障碍和慢性疼痛越来越被认为是普遍和有问题的并存疾病，了解睡眠障碍如何改变行为和奖励系统功能的情感测量可能会增加阿片类药物依赖患者治疗慢性疼痛的有限选择。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)获得实验性睡眠方法和睡眠障碍评估方面的专业知识；2)获得神经生物学和奖励系统评估方面的培训；3)获得阿片类药物依赖患者研究方面的培训；4)获得负责任进行研究方面的培训。拟议的短期开发活动将使应聘者能够通过提供必要的技能集来实现其长期目标：a)安全有效地操作睡眠；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)从生物行为角度自信地解释功能性奖励系统变化的证据；e)招募、保留并负责任地执行阿片依赖患者的研究方案；以及f)了解阿片成瘾的精神药理学基础和慢性共病疼痛的临床细微差别。建议的研究项目分为两个研究。研究1将在健康受试者的人内睡眠剥夺实验中建立一个睡眠干扰引起的奖赏系统功能障碍的基本行为模型。研究2将收集横断面试验数据，以确定在有慢性疼痛的阿片依赖患者与没有慢性疼痛的阿片依赖患者中，睡眠障碍与回报系统功能障碍的相关性是否更大。协调的培训和研究计划从逻辑上扩展了候选人之前在慢性肌肉骨骼疼痛的情绪调节方面的工作，并形成了一个新的研究方向，解决了我们目前对睡眠障碍如何影响奖赏系统功能，以及这一途径如何导致阿片类药物依赖患者慢性疼痛的理解中的空白。

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.