偏头痛，美国在研项目简述（2024）
Bringing medical advances from the lab to the clinic.
偏头痛（Migraine）是一种常见的慢性神经系统疾病，以反复发作的中至重度头痛为特征。头痛通常是单侧的，呈脉动性质，持续时间可以从几小时到几天。
活动性偏头痛的高峰发病年龄为40岁左右，其中35%左右的女性和15%左右的男性受到影响。
尽管偏头痛的治疗已取得一定进展，但其病因复杂、治疗响应个体差异大等特点使得临床上仍面临诸多挑战：
病因未明：尽管已知偏头痛与大脑的异常化学和神经信号有关，其确切病因仍不完全清楚，这限制了更有效治疗方法的开发。 治疗反应个体差异大：现有治疗方法在不同患者间的效果差异较大，且有些患者对常用的治疗药物不响应。 慢性化风险：部分患者的偏头痛会逐渐发展为慢性偏头痛，治疗难度增加，影响生活质量。 长期管理策略：如何有效地进行长期管理和预防偏头痛发作，尤其是在无法避免诱因的情况下，仍然是一个挑战。 并发症：偏头痛与多种心血管疾病、精神健康问题有关联，但这些并发症的管理和预防策略尚未充分研究。
未来的研究需进一步探索偏头痛的生物机制，以期开发更为个性化和有效的治疗方法。
CINCINNATI CHILDRENS HOSP MED CTR 的 POWERS, SCOTT W
WASHINGTON UNIVERSITY 的 NAHMAN-AVERBUCH, HADAS BETH ISRAEL DEACONESS MEDICAL CENTER 的 LEVY, DAN UNIVERSITY OF UTAH 的 BRENNAN, KEVIN CHRISTOPHER MASSACHUSETTS GENERAL HOSPITAL 的 HOULE, TIMOTHY T
麻省总医院 辛辛那提儿童医院医疗中心 华盛顿大学 贝斯以色列女执事医疗中心 犹他大学等
Migraine is a debilitating pain condition and ranks globally in the top five for years lived with disability. Approximately 15% of the general US population experiences migraine, with women afflicted approximately twice as often as men.
We propose an investigation that is responsive to PAR-19-315 through a goal of identifying and validating plasma-based biomarkers diagnostic of migraine and its potential subclasses.
During the R61 phase of the research, we will measure a comprehensive panel of >1300 plasma metabolites and 92 vascular related proteins among three groups of women from the Women’s Genome Health Study (WGHS): those with active migraine, non-migraine headache, and no headache symptoms. In these data, we will use state-of-the-art statistical modeling to identify plasma-based metabolite and protein signatures of migraine that formally discriminate individuals with active migraine from those never reporting headache and also those reporting non-migraine headache as well as among sub-classes of migraine defined by specific migraine symptoms, e.g. aura. Using existing genetic data, we will apply a genetic instrumental variable method termed “Mendelian Randomization” to assess whether these metabolite signatures may have causal effects on migraine.
During the R33 phase, we will develop and apply a validated assay(s) targeting the metabolite(s) and/or protein(s) identified in the R61 to perform an initial validation study our biomarker signature within a new cohort of men and women recruited for this project.
We anticipate that findings from the proposed research have the potential to help refine the analysis of response in clinical trials, optimize current prophylactic strategies, suggest new therapeutics, and resolve uncertainty in assignment of diagnostic aura status and other potential sub-classes of migraine.
Migraine is a highly prevalent and disabling disorder that affects ~15% of children and adolescents worldwide.
In the proposed study, we aim to identify the baseline factors determining migraine prognoses in adolescents (Aim 1), determine the hormonal, neural, and psychophysical changes related to migraine prognoses in adolescents (Aim 2a), and identify the temporal relationships between hormonal, neural, and psychophysical changes preceding vs. following changes in headache frequency (Aim 2b).
We hypothesize that male sex and greater CPM responses, lower amygdala-prefrontal cortex (PFC) FC, and higher testosterone levels at baseline will be associated with a decrease in headache frequency after two years.
We expect that adolescents with increased headache frequency will have a greater reduction in CPM efficiency, increased amygdala-PFC FC, and a smaller increase in testosterone levels compared to adolescents with a decrease or no change in headache frequency and healthy adolescents.
We expect smaller increases in testosterone levels to precede increases in headache frequency and greater reductions in CPM efficiency and increases in amygdala-PFC FC to follow increases in headache frequency.