Overview

• Prevalence: ∼ 17% of females and ∼ 6% of males [1]

• Peak incidence: 30–39 years [2][3]

• Migraine is the second most common type of headache.

• The exact pathophysiology is unclear. [5]

• Genetic predisposition

• Potential triggers

  • Certain food and beverages: alcohol, nicotine, citrus fruits, dairy products, food containing tyramine (e.g., chocolate, red wine)

  • Fasting, dehydration

  • Poor sleeping habits

  • Emotional stress

  • Weather changes

  • Hormonal changes in women: menstruation, hormone intake (oral contraceptive pills)

• The pathophysiology of migraine is not fully understood.

• Various factors are thought to contribute to the development and severity of migraines.

  • Activation of meningeal nociceptors

    • Dilatation of intracranial blood vessels → activation of meningeal nociceptors

    • Activation of the trigeminovascular pathway: activation of trigeminal neurons → release of vasoactive neuropeptides such as substance P or calcitonin gene-related peptide (CGRP) → vasodilatation and release of proinflammatory molecules (histamine, bradykinin, serotonin, prostaglandins) → neurogenic inflammation → activation of meningeal nociceptors [6]

    • Cortical spreading depression: excitation and inhibition of the cerebral cortex → changes in cortical enzymatic activity (proinflammatory molecules) → neurogenic inflammation → activation of meningeal nociceptors [7]

  • Dysregulation of pain sensitization in the trigeminal system (CN V): cortical spreading depression → dysregulation of trigeminovascular neurons → neurogenic inflammation → hypersensitization → nausea, loss of appetite, yawning, fatigue, anxiety, depression [8]

  • Genetic predisposition: in individuals with migraine, the brain does not have the ability to habituate itself to external stimuli (e.g., stress, hormonal changes) → hyperexcitable brain [7]

  • Activation of the autonomic nervous system: external physiological and emotional stimulation (e.g., hormonal changes, stress) → hypothalamic response to the change in homeostasis → hypothalamic neurons influence the autonomic nervous system → shift toward a parasympathetic tone → constriction and dilatation of intracranial, especially the meningeal, blood vessels [7]

Vasodilatation is now considered an epiphenomenon rather than the primary cause of migraine headache.