Impact and Mechansims of Migraine Comorbidites on Migraine Onset and Progression

描述(由申请人提供)：这是一份以患者为导向的研究事业发展奖的申请表。拟议项目的目标是为候选人提供所需的高级技能，以建立一个独立的偏头痛研究计划，评估影响偏头痛发生和发展的因素，以及如何改进偏头痛治疗。为了促进这一长期的职业目标，候选人将研究共病条件，特别是肥胖，对偏头痛发作和严重程度的影响，以及这种联系的潜在机制。候选人提出了一个全面的培训计划，包括由她的导师指导的教学、正式的课程作业、与个人顾问一起参加应用培训经验，以及参加研讨会和研讨会。具体的培训目标包括：(1)临床疼痛研究方面的高级培训，(2)分子蛋白质组学方法学方面的培训，(3)身体成分评估方面的培训，(4)生物统计学方面的培训，(5)神经流行病学方面的培训，以及(6)负责任的研究操作方面的培训。培训计划的执行将与一系列拟议的研究相协调，这些研究基于候选人收集的初步数据，证明了生育年龄个人中偏头痛和肥胖之间的流行病学联系，以及与炎症相关的脂肪因子(主要由脂肪组织中的脂肪细胞分泌的蛋白质)在慢性偏头痛与发作性偏头痛或对照组中的差异表达。这项拟议的研究将建立在这些初步发现的基础上，通过使用双能量X射线吸收测量仪和腹部MRI成像来研究肥胖和非肥胖偏头痛临床队列中脂肪因子的表达和身体组成，并与对照组进行比较。此外，一项基于社区的流行病学研究的数据也将被用来检查肥胖参与者新发偏头痛的相关因素。因此，这项拟议的应用将进一步定义偏头痛与肥胖之间的联系，确定偏头痛与肥胖之间的潜在神经生物学机制，并确定偏头痛的潜在新治疗靶点。

DESCRIPTION (provided by applicant): This is an application for a Mentored Patient-Oriented Research Career Development Award. The goal of the proposed project is to provide the candidate with advanced skills needed to establish an independent program of migraine research evaluating the factors that influence the generation and progression of migraine and how to improve migraine treatment. To facilitate this long-term career goal the candidate will examine the impact of co-morbid conditions, particularly obesity, on migraine onset and severity, as well as potential mechanisms for this association. The candidate proposes a comprehensive training plan, combining didactic instruction overseen by her mentors, formal coursework, participation in applied training experiences with individual advisors, and participation in seminars and workshops. Specific training goals include: (1) advance training in clinical pain research, (2) training in the methodologies of molecular proteomics, (3) training in body composition assessment, (4) training in biostatistics, (5) training in neuroepidemiology, and (6) training in the responsible conduct of research. The training plan will be executed in coordination with a proposed set of research studies that are based upon preliminary data collected by the candidate, demonstrating an epidemiological association between migraine and obesity in individuals of reproductive age as well as the differential expression of inflammatory-related adipokines (proteins secreted primarily from adipocytes in adipose tissue) in those with chronic migraine vs. those with episodic migraine or controls. The proposed research will build upon these preliminary findings by studying adipokine expression and body composition using dual energy x-ray absorptiometry and abdominal MRI imaging in a clinical cohort of obese and nonobese migraineurs as compared to controls. Additionally, data from a community-based epidemiological study will also be used to examine factors related to the development of new onset migraine in obese participants. The proposed application will therefore further define the migraine-obesity association, identify potential neurobiological mechanisms for the association of migraine with obesity and identify potential novel treatment targets for migraine.