• Marta Vila-Pueyo, Jan Hoffmann, Marcela Romero-Reyes, and Simon Akerman.
• Headache Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
• Cephalalgia. 2019 Nov 1; 39 (13): 1635-1660.

ObjectiveTo review and discuss the literature relevant to the role of brainstem structure and function in headache.BackgroundPrimary headache disorders, such as migraine and cluster headache, are considered disorders of the brain. As well as head-related pain, these headache disorders are also associated with other neurological symptoms, such as those related to sensory, homeostatic, autonomic, cognitive and affective processing that can all occur before, during or even after headache has ceased. Many imaging studies demonstrate activation in brainstem areas that appear specifically associated with headache disorders, especially migraine, which may be related to the mechanisms of many of these symptoms. This is further supported by preclinical studies, which demonstrate that modulation of specific brainstem nuclei alters sensory processing relevant to these symptoms, including headache, cranial autonomic responses and homeostatic mechanisms.Review FocusThis review will specifically focus on the role of brainstem structures relevant to primary headaches, including medullary, pontine, and midbrain, and describe their functional role and how they relate to mechanisms of primary headaches, especially migraine.

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