Abstract
BackgroundIncreased inflammatory cytokines and matrix metalloproteinases (MMPs) have been recently implicated in migraine. Inflammation may be a key player in the pathophysiology of migraine by altering blood-brain barrier (BBB) function. As an inflammation induced MMP, MMP-9 is involved in both BBB disruption and neuropathic pain, and is largely derived by neutrophil degranulation during neutrophil-BBB interaction. The tetracycline group of antibiotics may suppress MMP production and neutrophil degranulation.Methods/DesignWe hypothesize that migraine is a primary neuroinflammatory disorder. We will address this theory by measuring serum biomarkers in healthy controls and after one of three abortive therapy strategies for acute migraine attacks and inter-ictally. We intend to investigate known neuroinflammatory biomarkers with a focus on BBB breakdown during acute migraine attacks and assess marker responses to conventional treatment (triptans), novel MMP targeted therapy (doxycycline), or a combination of triptan and doxycycline. We will measure the effects of the interventions on neuroinflammatory markers for acute migraine attacks, clinical outcomes (headache relief and recurrence) for acute migraine attacks, inter-ictal neuroinflammatory load per serum biomarkers in migraineurs versus healthy controls, and neuroinflammatory markers correlation with headache duration and peak headache intensity during acute migraine attacks.Discussion To our knowledge, this trial will be the first systematic study on the use of a MMP inhibitor in episodic migraine. Our pilot project data will supplement future projects investigating novel therapeutic strategies such as MMP inhibitors in both migraine acute treatment and prevention.Trial RegistrationClinicalTrials.gov NCT01653522, registered 07/23/2012.
Highlights
Increased inflammatory cytokines and matrix metalloproteinases (MMPs) have been recently implicated in migraine
Inflammation may be a key player in the pathophysiology of migraine by altering blood-brain barrier (BBB) function
Methods/Design: We hypothesize that migraine is a primary neuroinflammatory disorder. We will address this theory by measuring serum biomarkers in healthy controls and after one of three abortive therapy strategies for acute migraine attacks and inter-ictally
Summary
Migraine is a common neurovascular disorder that affects over 30 million Americans. There is significant economic impact secondary to headacherelated disability [1]. The BBB protects the brain against compounds and pathogens in the blood stream and maintains central nervous system homeostatsis. The origin of MMP-9 in migraine patients remains unknown, as does the effect of acute migraine treatment targeting MMP-9. Compounds such as triptans and magnesium may not cross an intact BBB, their utility in migraine may be in the setting of BBB disruption. Todd Rozen of the Geisinger Medical Group has written on doxycycline use as an antiinflammatory drug for primary headache disorders, especially new daily persistent headache He only published one abstract on his open label use [26], no peer-reviewed paper, and referred to it in a recent review [27]
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