The under-recognized but essential role of the limbic system in the migraine brain: a narrative review

Migraine is a very common brain disorder that causes throbbing headaches of moderate-to-severe intensity that are associated with a variety of symptoms like nausea, vomiting, multisensory hypersensitivity, dizziness, fatigue, cognitive dysfunction, and sleep problems, among others. The diverse symptomatology of migraine hints at the complexity of the disease and implies the involvement of multiple nervous system components, including the somatosensory, executive, autonomic, endocrine, and arousal networks. The major pathophysiologic mechanisms responsible for migraine attacks have been identified over the past several decades, and the elucidation of these mechanisms has brought about remarkable advances in therapeutic strategies, including the creation of anti-calcitonin gene-related peptide therapeutics—the newest addition to the list of anti-migraine therapies. However, current knowledge on the pathophysiologic mechanisms of migraine remains incomplete and treatments are only partially effective, with the involvement of the limbic system being less often recognized and symptoms related to the limbic system being undertreated. This article reviews recent advances in understanding the pathophysiologic roles of the limbic system in migraine and how the limbic system contributes to clinical features observed in migraine.