Migraine Pathophysiology

Migraine is the leading cause of years lost due to disability in individuals aged 15 to 49 years. Much has changed over the last three decades about our understanding of this complex neurological disorder. Various phases of migraine have been characterized and are the focus of this review. The premonitory phase involves bothersome symptoms experienced hours to days before migraine pain. Behavioral changes and functional neuroimaging studies point toward hypothalamic involvement during the premonitory and other migraine phases. Migraine aura is a disruptive, reversible neurological phenomenon that affects up to one-third of all migraineurs, and can overlap with the headache phase. The mechanism responsible for this phase is thought to be cortical spreading depolarization through the cortex. This process leads to temporary disruptions in ion homeostasis and the ensuing neuronal dysfunction. The headache phase involves activation of the trigeminocervical complex. Neuropeptides are implicated in trigeminal activation, and calcitonin gene-related peptide in particular has become a promising target of therapeutic intervention for migraine. The final phase of migraine is the postdrome, the period of time from the resolution of headache symptoms until return to baseline following a migraine. People often report neuropsychiatric, sensory, gastrointestinal, and general symptoms during this time, which can limit activity. Elucidating the neuroanatomical, chemical, and neuroimaging correlates of these migraine phases allows for an improved comprehension of the underlying changes associated with migraine symptomatology and can assist with evaluation of arising therapeutics for migraine management.