Currently, three major focus areas of the Migraine Resarch Program at Mayo Clinic include:
- Genomics of migraine
Genomics of migraine
In contrast to the candidate gene studies carried out since the mid-1990s, the last few years have seen the rise of genetic studies, which assume polygenic variability with a small effect are of importance in human disease.
Genotyping allows researchers to study genetic variations and mutations that may contribute to migraines.
A genomic library is a collection of biological samples (such as blood) and health information that is used in research to gain a better understanding of how a person's genes (DNA) may influence overall health and wellness.
The Mayo Clinic Migraine Genomic Library focuses on identifying genetic differences that might affect an individual's risk of experiencing certain migraine symptoms and on examining how differences in DNA influence responses to different migraine medications. By gaining a deeper understanding of the genetic causes of migraine, physicians can offer better treatment for migraine patients.
The Migraine Genomic Library research team is currently enrolling participants who experience migraine, as well as individuals who do not experience migraine.
That environmental factors have a huge impact on people with migraine is undeniable, both in terms of their importance in triggering acute attacks and their impact on the course of the disorder throughout a person's life.
Trigger factors from the internal environment (for example, gonadal hormonal fluctuations, changes in blood glucose with fasting) as well as from the external environment (for example, changes in barometric pressure, environmental stress, exposure to exogenous chemicals such as nitric oxide, histamine, or other chemicals in foods or food additives) are well known modulators of migraine. How these environmental factors impact migraine remains unknown.
There is increasing evidence that environmental factors may actually impact people at a basic cellular level through what are known as epigenetic effects on the DNA. These include epigenetic methylation (adding a –CH3 group) of the DNA, the basic instruction set for cellular activity and alterations of the winding pattern of DNA around histone proteins inside the cell nucleus. Both of these alterations, which can be caused by environmental exposures, may result in altered expression of the DNA and subsequent changes in activity of the cells within the brain. This new emerging field, thus far unexplored in people with migraine, promises to begin to explain how the environment affects the course of migraine in an individual.
Mayo investigators are uniquely well positioned for future epigenetic studies because of its large library of genomic DNA linked to detailed clinical phenotypic information stored as elemental data.
Neuoimaging-based investigations on migraine pathophysiology recognize that migraine may clinically exist as either an episodic or chronic neurologic disorder, of which headache is only one feature.
Pain processing in the central nervous system is complex and involves a synthesis of sensory-discriminative, emotional-affective and cognitive-evaluative components represented in a neural network termed the pain matrix. Further, migraine may be associated with aura referable to all lobes of the brain, in addition to autonomic symptoms. Therefore, neuroimaging biomarkers in migraine need to capture functional information elements across multiple neuroanatomic regions.
Neuroimaging research has driven major advances in the understanding of many important aspects of migraine pathophysiology, including generation, chronification, consequences and treatment.
Clinicians and researchers alike have long suspected that dynamic extra- and intracranial arterial changes are associated with migraine attacks.
Functional imaging techniques are able to capture dynamic, real-time data regarding cerebral blood flow, neuronal activity and metabolism.
The Mayo team is studying application of the following imaging techniques to study episodic and chronic migraine, both during attacks and in the attack-free state:
- High-resolution magnetic resonance angiography (MRA)
- Perfusion-weighted imaging (PWI)
- Single-photon emission computerized tomography (SPECT)
- Functional magnetic resonance imaging (fMRI)
- Positron emission tomography (PET)
- Diffusion-weighted imaging (DWI)
- Blood-oxygen-level-dependent (BOLD) imaging
Major advances in the understanding of migraine pathophysiology have emerged from neuroimaging research.