Studies of familial hemiplegic migraine transgenic mouse models and patients to investigate the crosstalk between sensory neurons and neuroinflammatory cells in trigeminal ganglia in relation to migraine pain

According to the WHO migraine is a common disorder affecting 15% adults in the Western World. Despite recent advances in its treatment, a significant number of patients still experience recurrent headache attacks, that can become increasingly frequent with associated health risks, or that are even incorrectly diagnosed. To improve migraine therapy it is necessary to act on three fronts: 1. blocking the acute attack; 2. preventing recurrence; 3. improving diagnosis. These are daunting tasks when considering how diverse the population of migraneurs is, and that clinical studies cannot be patient-invasive. Recent genetic studies have demonstrated that a monogenic mutation is responsible for hereditary migraine subtypes, the most frequent of which is familial hemiplegic migraine1 (FHM1). This discovery led to produce a transgenic mouse model in which a single gene mutation found in FHM1 patients replicates relevant migraine symptoms, including trigeminal pain hypersensitivity as shown in our labs. We wish to combine basic studies of this model with clinical investigations of FHM1 blood samples to find out what cellular and molecular mechanisms predispose trigeminal neurons to signal strong headache, whether there is a hidden pathological process in trigeminal ganglia between attacks, and what substances detected in the blood of FHM1 patients may be responsible for trigeminal ganglion hypersensitivity. We will then study what chemicals found in transgenic mouse ganglia and reputed to facilitate pain are also present in FHM1 blood. Our focus is on ATP-activated pain receptors of ganglion neurons and closely associated satellite cells that work together as a functional unit in which we posit that a latent pathological change confers increased pain sensitivity and predisposition to attacks. Identification of chemicals in FHM1 blood may help to establish migraine biomarkers in relation to the disease stage and, thus, be helpful for diagnostic purposes and to correctly address future therapeutic interventions.