Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain

Pain. 2013 Dec:154 Suppl 1:S44-53. doi: 10.1016/j.pain.2013.07.021. Epub 2013 Jul 25.


Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory, and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. In addition, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex.

Keywords: Aura; Cortical spreading depression; Headache; Meningeal nociceptors; Migraine; Neuronal excitability; Pain modulation; Photophobia; Sensitization; Trigeminovascular system.

Publication types

  • Review

MeSH terms

  • Afferent Pathways / pathology
  • Afferent Pathways / physiopathology
  • Animals
  • Brain / pathology
  • Brain / physiopathology*
  • Cerebral Arteries / innervation*
  • Cerebral Arteries / physiopathology*
  • Cortical Spreading Depression*
  • Humans
  • Migraine Disorders / physiopathology*
  • Models, Cardiovascular
  • Models, Neurological
  • Pain / pathology
  • Pain / physiopathology*
  • Trigeminal Nerve / physiopathology*