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Headache. 2019 Jul;59 Suppl 2:50-65. doi: 10.1111/head.13585.

Emerging Treatment Targets for Migraine and Other Headaches.

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Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.


Migraine is a complex disorder that is characterized by an assortment of neurological and systemic effects. While headache is the most prominent feature of migraine, a host of symptoms affecting many physiological functions are also observed before, during, and after an attack. Furthermore, migraineurs are heterogeneous and have a wide range of responses to migraine therapies. The recent approval of calcitonin gene-related-peptide based therapies has opened up the treatment of migraine and generated a renewed interest in migraine research and discovery. Ongoing advances in migraine research have identified a number of other promising therapeutic targets for this disorder. In this review, we highlight emergent treatments within the following biological systems: pituitary adenylate cyclase activating peptdie, 2 non-mu opioid receptors that have low abuse liability - the delta and kappa opioid receptors, orexin, and nitric oxide-based therapies. Multiple mechanisms have been identified in the induction and maintenance of migraine symptoms; and this divergent set of targets have highly distinct biological effects. Increasing the mechanistic diversity of the migraine tool box will lead to more treatment options and better patient care.


delta opioid receptor; kappa opioid receptor; nitric oxide synthase; orexin; pituitary adenylate cyclase activating peptide; soluble guanylyl cyclase


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