Career Development in Biobehavioral Risk Factors for Pain: Sleep and the HPA Axis

描述（由申请人提供）：有大量新兴且令人震惊的证据证明睡眠不足在诱发和持续疼痛报告中的作用，以及疼痛在诱发和持续睡眠障碍中的作用;三分之一的成年人归因于每月因疼痛而睡眠不足超过20小时。鉴于我们的社会有一个快速增长的睡眠债务，其次是减少睡眠机会的生活方式，长期睡眠限制对健康的影响，特别是疼痛是巨大的。将疼痛和睡眠障碍联系在一起的机制尚未得到很好的理解，这极大地限制了改善疼痛和睡眠障碍以及改善功能和生活质量的循证策略。拟议的职业发展奖是候选人长期目标的关键下一步，成为一名独立的研究科学家，进行床边到长凳的转化研究，其中疼痛，睡眠障碍和其他症状的前因和后果在受控实验室环境中的各种急性和慢性疾病状态的背景下进行机械研究。为了实现这一长期目标，候选人必须继续通过神经免疫学和神经科学课程，以及各种啮齿动物疼痛模型和啮齿动物睡眠分析的额外指导和技能，在临床前研究中奠定基础。在整个职业发展奖励期间，候选人将在盖勒博士的监督下工作。Page博士和Mark R. Opp，密歇根大学，临床前疼痛模型和啮齿动物睡眠采集和分析专家，分别。本研究计划使用雄性和雌性大鼠，旨在确定：（1）睡眠限制对紫杉醇诱导的机械超敏反应的影响;（2）大鼠在紫杉醇诱导的机械超敏反应引起的睡眠变化中的HPA轴反应性。成功完成职业发展和研究计划将促进独立科学家的发展，准备领导跨学科团队应对共同发生的疼痛和睡眠障碍的复杂挑战。 公共卫生相关性：疼痛和睡眠障碍是重要的公共卫生问题。关于疼痛和睡眠障碍之间的联系机制，或者相对于睡眠障碍的疼痛是否存在性别差异，我们知之甚少。这项研究的结果有可能指导制定有针对性的干预措施，以减少疼痛和睡眠障碍，并改善忍受疼痛和睡眠障碍的人的功能和生活质量。

DESCRIPTION (provided by applicant): There is a burgeoning and alarming body of evidence that testifies to the role of sleep loss in precipitating and perpetuating pain reports, and to the role of pain in precipitating and perpetuating sleep disturbance; 1 in 3 adults attribute a sleep loss of more than 20 hours each month due to pain. Given that our society has a rapidly growing sleep debt, secondary to lifestyles that reduce sleep opportunities, the implications of chronic sleep restriction on well being in general and pain in particular are immense. The mechanisms that link together pain and sleep disturbance are not well understood, greatly limiting evidence-based strategies to ameliorate pain and sleep disturbance, and improve functioning and quality of life. The proposed career development award is the pivotal next step in the candidate's long term goal to become an independent research scientist who conducts bedside-to-bench translational research in which the antecedents and consequences of pain, sleep disturbance, and other symptoms are mechanistically studied in the context of a variety of acute and chronic disease states within a controlled laboratory environment. In order to accomplish this long term goal, the candidate must continue building her foundation in pre-clinical research through coursework in neuroimmunology and neuroscience, and additional mentoring and skills in a variety of rodent pain models and rodent sleep analysis. Throughout the career development award period, the candidate will work under the supervision of Dr. Gayle G. Page, Johns Hopkins University, and Dr. Mark R. Opp, the University of Michigan, experts in pre-clinical pain models and rodent sleep acquisition and analysis, respectively. The specific aims of the research plan, using male and female rats, are to determine: (1) The effects of sleep restriction on paclitaxel-induced mechanical hypersensitivity; and (2) HPA axis responsivity of rats in sleep changes due to paclitaxel-induced mechanical hypersensitivity. Successful completion of the career development and research plans will foster the development of an independent scientist, poised to lead interdisciplinary teams in responding to the complex challenges of co-occurring pain and sleep disturbance. PUBLIC HEALTH RELEVANCE: Pain and sleep disturbance are significant public health problems. Little is known about the mechanisms that link pain and sleep disturbance, or whether there are sex differences in pain relative to sleep disturbance. The results from this study have the potential to guide the development of targeted interventions to reduce pain and sleep disturbance, and improve functioning and quality of life for persons who endure them.