The mysterious link between migraine aura and migraine headache

Migraine aura - manifesting as transient, neurological disturbances - presents a complex and unresolved relationship with migraine headache. Cortical spreading depolarization (SD), recognized as the mechanism underlying aura symptoms, has been shown to trigger head pain through activation of trigeminal nociceptors in animal models. However, recent clinical data challenge the notion that aura causes migraine headache in patients. In this Essay, we critically examine the pathophysiology of migraine aura and migraine headache, exploring evidence from clinical observations, (genetic) mouse models, and pharmacological studies. We also discuss the role of SD, the trigeminovascular system, and the impact of pharmacological agents that both trigger and treat migraine attacks. Our essay highlights the complexities and conflicting data surrounding the interplay between aura and headache, emphasizing the need for further research to unravel this mystery and improve therapeutic strategies for individuals with migraine.