From the Guidelines
Migraine pathophysiology involves a complex interplay of peripheral and central activation of the trigeminovascular system, with cortical spreading depression thought to be the underlying neurophysiological substrate of migraine aura. The condition is believed to manifest clinically as recurrent attacks of headache with accompanying symptoms, including transient neurological disturbances referred to as migraine aura in approximately one third of individuals with migraine 1. This complex pathophysiology is supported by the fact that migraine is a highly disabling primary headache disorder with a 1-year prevalence of ~15% in the general population, and is responsible for more disability than all other neurological disorders combined 1.
Key aspects of migraine pathophysiology include:
- Activation of the trigeminovascular system, which triggers the release of inflammatory neuropeptides like calcitonin gene-related peptide (CGRP) 1
- Cortical spreading depression, a wave of neuronal depolarization followed by inhibition, which is believed to underlie migraine aura and may activate the trigeminovascular system 1
- Genetic factors, with mutations in ion channel genes contributing to familial hemiplegic migraine 1
- Neurotransmitter imbalances, particularly involving serotonin, dopamine, and glutamate, which further contribute to migraine development 1
- Central sensitization in the trigeminal nucleus caudalis and thalamus, which explains symptoms like allodynia 1
- Environmental triggers, such as stress, hormonal fluctuations, certain foods, and sleep disturbances, which can precipitate attacks by affecting these underlying mechanisms 1
Overall, the pathophysiology of migraine is complex and multifaceted, involving both neural and vascular mechanisms, and is supported by recent evidence from a consensus statement on the diagnosis and management of migraine 1.
From the Research
Migraine Pathophysiology Overview
- Migraine is a complex neurological disorder characterized by multiple phases, including premonitory, aura, headache, postdrome, and interictal phases 2
- The pathophysiology of migraine involves a complex interplay between various cortical and subcortical brain regions, including the hypothalamus and brainstem nuclei that modulate nociceptive signaling 2
Key Brain Regions and Systems Involved
- The trigeminovascular system, a pathway that is well characterized, is involved in the headache phase of migraine 2, 3
- The hypothalamus and brainstem nuclei play a crucial role in modulating nociceptive signaling 2
- The brain's neurochemistry, including monoaminergic and peptidergic systems, such as those involving calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide, are implicated in migraine pathophysiology 4
Neurotransmitters and Neuropeptides
- Calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and substance P are sensory neuropeptides that may contribute to neurogenic inflammation and peripheral and central sensitization of the trigeminal system 3
- Sympathetic and parasympathetic neuropeptides, such as neuropeptide Y and vasoactive intestinal peptide, may also play a role in migraine pathophysiology 3
Current Understanding and Future Directions
- Recent advances in human migraine research have provided novel insights into migraine attack initiation, neurochemistry, neuroanatomy, and therapeutic substrates 4
- Targeting various therapeutic substrates within the complex networks involved in migraine pathophysiology provides an exciting avenue for future migraine therapeutics 4