Sensory Amplifications as Biomarkers of Migraine Progression

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PROJECT SUMMARY/ABSTRACT Migraine affects an estimated 12-15% of the world population. Chronic migraine, which completely disrupts the lives of sufferers, affects close to 3% and accounts for the vast majority of the disability and cost of the disorder. It also contributes to the epidemic of opioid overuse that has been a major impediment to pain care in the past 20 years. One of the highest priorities in migraine research is to understand the progression from episodic to chronic migraine, so it can be prevented. Current clinical criteria are useful for diagnosing episodic and chronic migraine, but they have not necessarily been predictive of progression, and thus are not helpful in identifying subjects at risk.This proposal aims to discover and validate biomarkers of migraine progression. Our key hypothesis is that the sensory amplifications that characterize migraine – photophobia, phonophobia, allodynia, and others – constitute psychophysical and physiological biomarkers, and that they will better predict migraine progression than the current clinically-based gold standard. Our group has shown that different individual sensory amplifications scale with disease severity; our preliminary data shows that their sensitivity is amplified when they are combined. We also propose that though psychophysical/physiological biomarkers are conceptually novel, they are also practical in the clinical setting and indeed consistent with routine neurological evaluation. Our group’s expertise spans the full range of sensory amplifications in migraine and importantly incorporates expertise in developing and validating practical instruments for migraine research and clinical use. The R61 Phase (3 years; 300 high frequency episodic migraineurs followed longitudinally; Aims 1 and 2) will deploy a multimodal, multilevel assessment of sensory amplifications with the goal of identifying the most sensitive measures for prognostication. Aim 1 will provide performance parameters of sensory amplifications as biomarkers of migraine progression. Aim 2 will develop a tool (predictive model) for prognosticating disease progression. This predictive model will explicitly consider sex, aura, and medication use/overuse, as these variables are also well-known to contribute to both sensory amplifications and chronification. Milestones for transition from R61 to R33 will include successful development of a refined battery of sensory tests for formal validation as biomarkers in the R33 Phase. If milestones are met, the R33 Phase (2 years; 100 subjects each in US and Brazil; Aim 3) will validate the refined battery, with the goal of providing optimized tools for use in clinical trials. Thus, Aim 3 will confirm (or refute) the prognostic predictive utility of the model identified in the R61 Phase in two different populations. If successful, this work will deliver the first ever validated prognostic tools to be used in migraine. Their purpose will be to help prevent the progression of episodic to chronic migraine, reduce the attendant opioid overuse that this progression often brings, and ultimately mitigate the overwhelming burden of chronic migraine on patients and society.