Episodic migraine (EM) is the most prevalent neurologic disorder, affecting 12% of the adult population. Positive and negative neurological symptoms may precede or accompany head pain though the pain of migraine may ensue without warning signs. Autonomic, gastrointestinal, somatosensory and cognitive changes many accompany migraine, compounding the impact and burden of EM. Imaging and neurophysiology studies confirm involvement of cortical, subcortical, brainstem and central and peripheral trigeminal structures. Effective treatments have been slow to emerge and are few in number. EM is co-morbid with mood disorders as well as a host of Complex Persistent Pain Conditions (CPPCs) including IBS, FM, WS and TMD. Peripheral and central sensitization occur during attacks while Quantitative Sensory Testing is typically normal between attacks. Evoked potentials show decreased habituation between attacks. Although genes have been identified for Familial Hemiplegic Migraine, implicating changes in glial and synaptic function in that condition, no gene has been identified in common migraine. EM has an increased prevalence in patients with inflammatory/immunologic diseases and is associated with structural changes in deep white matter at times. EM becomes chronic in some with resultant permanent changes in brain structures subserving pain recognition and modulation. We propose that EM shares behavioral, phenotypic and genetic factors with other CPPCs including FM, IBS, W S and TMD. In addition, we expect that these factors will predict variations in testable cortical responses. Our objective is to fully characterize a large group of patients with EM. We have assembled a multi-disciplinary team of investigators with expertise in neurology, pain medicine, neurophysiology, orofacial pain and dentistry, genetics, psychophyslcs, psychology, biostatistics and epidemiology. The proposed aims will provide converging evidence for the mechanisms underlying EM with respect to: 1) psychosocial profiles in EM commonly observed with other CPPCs;2) response characteristics and adaptation to sensory stimuli;and 3) candidate genes that influence pain, sensory processing, and psychological profiles. This evidence will guide development of mechanism-based treatments for EM and other prevalent, disabling and painful disorders.

National Institute of Health (NIH)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of North Carolina Chapel Hill
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