Migraine Onset in Adolescent Girls - Project Summary Migraine is one of the most common chronic pain conditions worldwide, but prevalence differs based on sex and age, with prevalence of migraine being higher in females. In addition to female sex, family history of migraine represents a further risk factor for migraine. However, the factors which contribute to or protect from migraine onset remain uncharacterized, and it is not yet possible to predict whether an individual will experience migraine onset, even among individuals with both risk factors. Thus, this study aims to investigate: Aim 1 – identify the psychophysical and neural factors which can predict migraine onset in adolescent girls; Aim 2a – determine the hormonal, psychophysical, and neural changes associated with migraine onset; and Aim 2b – characterize the temporal relationships between hormonal, psychophysical, and neural changes preceding vs. following migraine onset. Preliminary data support the use of psychophysical and neural factors as predictors of migraine onset. In addition, changes in pain sensitivity and in the functional connectivity of the amygdala are observed in patients with migraine and following changes in headache frequency, and thus support the use of these assays for the investigation of longitudinal changes related to migraine onset. Study participants will be healthy girls (age 10–13) with either a family history of migraine (Fam-His, N = 160) or with no family history of migraine (No-Fam-His, N = 40). In this study, we will perform assessments of psychophysical (pressure pain thresholds [PPT] and conditioned pain modulation [CPM]), neural (functional connectivity [FC] of the amygdala), and hormonal (testosterone levels) factors at baseline, and at 1- and 2-year follow-up time points. For all study visits, participants will also meet with a pediatric headache/pain specialist to determine whether or not they meet the diagnosis criteria for migraine (participants meeting diagnosis criteria at baseline will be excluded from the study). We hypothesize that a pre-existing pronociceptive psychophysical (lower PPT and lower inhibitory capabilities) and neural (greater FC between the right- amygdala and posterior cingulate cortex) profile at baseline will predispose Fam-His girls to migraine onset during adolescence and can be used to predict this onset. We expect that after 2 years, Fam-His girls diagnosed with migraine will have distinct psychophysical, neural, and hormonal changes as compared to those with no migraine onset and No-Fam-His girls. Moreover, we predict that lower increase in testosterone levels will precede migraine onset, while further transition towards a pronociceptive profile will be observed after migraine onset (reduction in PPT and CPM responses, and increase in amygdala FC). Early identification of individuals most likely to be diagnosed with migraine will facilitate the development of a precision medicine approach, allowing for the implementation of early preventive strategies, thereby reducing patient burden and healthcare system costs. In addition, identifying the sensory, neural, and hormonal mechanisms associated with migraine onset will be foundational to the development of novel migraine treatments.
