Impact and Mechansims of Migraine Comorbidites on Migraine Onset and Progression

描述（由申请人提供）：这是一个指导病人为导向的研究职业发展奖的申请。拟议项目的目标是为候选人提供建立偏头痛研究独立项目所需的高级技能，评估影响偏头痛产生和进展的因素以及如何改善偏头痛治疗。为了促进这一长期的职业目标，候选人将研究合并症，特别是肥胖，对偏头痛发作和严重程度的影响，以及这种关联的潜在机制。候选人提出一个全面的培训计划，结合由她的导师，正式课程，与个人顾问应用培训经验的参与，并参加研讨会和讲习班监督教学。具体的培训目标包括：（1）临床疼痛研究的高级培训，（2）分子蛋白质组学方法的培训，（3）身体成分评估的培训，（4）生物统计学的培训，（5）神经流行病学的培训，以及（6）负责任的研究行为的培训。培训计划的执行将与根据候选人收集的初步数据拟定的一套研究相协调，证明了育龄个体中偏头痛和肥胖之间的流行病学关联以及炎症相关脂肪因子的差异表达（主要从脂肪组织中的脂肪细胞分泌的蛋白质）在患有慢性偏头痛的那些人与患有发作性偏头痛的那些人或对照组中的差异。拟议的研究将建立在这些初步研究结果的基础上，通过研究脂肪因子的表达和身体组成，使用双能X射线吸收测定法和腹部MRI成像，在肥胖和非肥胖偏头痛患者的临床队列中与对照组进行比较。此外，来自社区流行病学研究的数据也将用于研究肥胖参与者新发偏头痛的相关因素。因此，所提出的申请将进一步定义偏头痛-肥胖症关联，鉴定偏头痛与肥胖症关联的潜在神经生物学机制，并鉴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.