Central Pain Mechanisms in Primary Dysmenorrhea

描述（由申请人提供）：拟议的指导患者导向研究职业发展奖（K23）题为“原发性痛经的中枢疼痛机制”的候选人是加州大学洛杉矶分校David Geffen医学院的临床讲师。这个为期五年的奖项旨在帮助候选人过渡到独立的临床科学家职业生涯，并通过探索青春期女孩和年轻成年女性原发性痛经（PD）的中枢性疼痛机制，扩大候选人在儿科疼痛方面的背景和培训。候选人的近期职业目标是获得妇女健康和慢性盆腔疼痛（特别是痛经）方面的培训和研究经验，使用复杂的疼痛评估技术来评估兴奋性和抑制性中枢疼痛过程，以及唾液评估和分析压力和性激素。她的长期职业目标是成为一名独立的研究人员，在与女性健康相关的疼痛机制方面拥有专业知识，通过解开一种非常常见但研究不足的疾病（PD）的疼痛过程来推进慢性疼痛领域，并为最终的R01应用程序获取数据，重点是测试青少年和成人PD的潜在行为干预措施。候选人已经确定了全国知名的导师作为其指导团队的一部分，其中包括一名儿童慢性疼痛专家，一名专门研究骨盆疼痛的产科医生/妇科医生，以及一名在压力心理生理测量方面的权威心理学家。指导小组的其他成员将在痛经、盆腔疼痛与其他慢性疼痛的关系、唾液压力和性激素的评估和分析等方面提供指导。除了正式和非正式的指导外，候选人还在国家认可的大学和医院工作，因此职业发展计划包括参加生殖内分泌学的教学和诊所，课程，研讨会和会议，产科/妇科，压力心理生理学，定性研究方法，研究课题的伦理考虑，拨款写作和职业发展，以及数据分析的统计方法。该候选人提出的研究涉及比较青春期和年轻成年女孩（16-21岁）在月经周期的三个阶段（月经、排卵期、黄体期）中患有和不患有PD的青少年和年轻成年女孩，通过各种标准化的实验性疼痛测试范式，旨在评估疼痛敏感性和中枢兴奋和抑制机制。该项目的具体目标是：1)确认PD女性疼痛敏感性增强的研究结果；2)评估PD女性和非PD女性中枢兴奋性和抑制性疼痛调节的差异；3)检测有PD和无PD的aya患者自主神经系统（ANS）和下丘脑-垂体轴（HPA）对疼痛反应的差异；4)评估心理因素（抑郁、焦虑和情绪调节）在两组疼痛反应中的作用。这项创新的研究使用了最近发展的疼痛范式来更好地理解青少年和女性PD患者如何以及为什么经历疼痛。此外，这项研究是同类研究中首次探索PD在整个发育谱中的疼痛反应，这有可能确定未来慢性疼痛问题发展的风险个体，并为新的干预和预防策略提供信息。从候选人拟议的研究和职业发展计划中获得的培训和经验将提供关键的早期职业支持，使候选人能够充分发展成为一名成功的独立研究人员，能够获得校外资金，并在妇女健康和疼痛方面建立长期的研究生涯。

DESCRIPTION (provided by applicant): The candidate for the proposed Mentored Patient-Oriented Research Career Development Award (K23) entitled 'Central Pain Mechanisms in Primary Dysmenorrhea' is a clinical instructor at the David Geffen School of Medicine at the University of California, Los Angeles. This five year award is expected to help the candidate transition to an independent career as a clinical scientist and to expand on the candidate's background and training in pediatric pain by exploring central pain mechanisms in adolescent girls and young adult women with primary dysmenorrhea (PD). The candidate's immediate career goals are to gain training and research experience in women's health and chronic pelvic pain (specifically, dysmenorrhea), using complex pain assessment techniques designed to evaluate excitatory and inhibitory central pain processes, and salivary assessment and analysis of stress and sex hormones. Long-term career goals are to become an independent investigator with expertise in pain mechanisms related to women's health, advance the field of chronic pain by disentangling pain processes in a highly common but understudied condition (PD), and obtain data for an eventual R01 application focused on testing potential behavioral interventions for adolescents and adults with PD. The candidate has identified nationally renowned mentors as part of her mentoring team, including an expert in chronic pain in children, an obstetrician/gynecologist who specializes in pelvic pain, and a psychologist who is an authority on psychophysiological measurement of stress. Other members of the mentoring team will provide guidance in dysmenorrhea and the relationship of pelvic pain to other chronic pain conditions, and salivary assessment and analysis of stress and sex hormones. In addition to formal and informal mentoring, the candidate is located at a nationally recognized university and hospital, such that the career development plan includes attending reproductive endocrinology didactics and clinic, classes, seminars, and meetings in obstetrics/gynecology, psychophysiology of stress, qualitative research methods, ethical considerations for research subjects, grant writing and career development, and statistical approaches to data analysis. The candidate's proposed research involves comparing adolescent and young adult girls (ages 16-21) with and without PD during each of 3 phases of the menstrual cycle (menstruation, ovulatory, luteal) across a variety of standardized experimental pain testing paradigms designed to evaluate pain sensitivity and central excitatory and inhibitory mechanisms. The specific aims for this project are: 1) to confirm previous findings of enhanced pain sensitivity in women with PD, 2) to evaluate differences in central excitatory and inhibitory pain modulation in women with and without PD, and 3) to test for differences in autonomic nervous system (ANS) and hypothalamic-pituitary axis (HPA) responses to pain in AYAs with and without PD, and 4) to assess the role of psychological factors (depression, anxiety, and emotion regulation) in relation to pain responses in both groups. This innovative study uses recently developed pain paradigms to better understand how and why adolescents and women with PD experience pain. In addition, this study is the first of its kind to explore pain responses in PD across the developmental spectrum, which has the potential to identify individuals at risk for the development of future chronic pain problems and inform new interventions and prevention strategies. The training and experience gained from the candidate's proposed research and career development plan will provide the critical early career support necessary for the candidate to fully develop as a successful independent researcher capable of obtaining extramural funding and establishing a long-term research career in women's health and pain.