| Summary: | Migraine results in an enormous burden on individuals and societies due to its high prevalence, significant disability, and considerable economic costs. Current treatment options for migraine remain inadequate, and the development of novel therapies is severely hindered by the incomplete understanding of the mechanisms responsible for the pain. The sensory innervation of the cranial meninges is now considered a key player in migraine headache genesis. Recent studies have significantly advanced our understanding of some of the processes that drive meningeal nociceptive neurons, which may be targeted therapeutically to abort or prevent migraine pain. In this review we will summarize our current understanding of the mechanisms that contribute to the genesis of the headache in one migraine subtype – migraine with aura. We will focus on animal studies that address the notion that cortical spreading depression is a critical process that drives meningeal nociception in migraine with aura, and discuss recent insights into some of the proposed underlying mechanisms.
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