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Rigshospitalet - a part of Copenhagen University Hospital
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Pathophysiological Mechanisms in Migraine and the Identification of New Therapeutic Targets

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  1. Targeting BKCa Channels in Migraine: Rationale and Perspectives

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  2. Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis

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  3. Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential

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  1. Ovariectomy reduces vasocontractile responses of rat middle cerebral arteries after focal cerebral ischemia

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  2. CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine

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  3. Hormonal influences in migraine - interactions of oestrogen, oxytocin and CGRP

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Migraine is a strongly disabling disease characterized by a unilateral throbbing headache lasting for up to 72 h for each individual attack. There have been many theories on the pathophysiology of migraine throughout the years. Currently, the neurovascular theory dominates, suggesting clear involvement of the trigeminovascular system. The most recent data show that a migraine attack most likely originates in the hypothalamus and activates the trigeminal nucleus caudalis (TNC). Although the mechanisms are unknown, activation of the TNC leads to peripheral release of calcitonin gene-related protein (CGRP), most likely from C-fibers. During the past year monoclonal antibodies against CGRP or the CGRP receptor have emerged as the most promising targets for migraine therapy, and at the same time established the strong involvement of CGRP in the pathophysiology of migraine. The viewpoint presented here focuses further on the activation of the CGRP receptor on the sensory Aδ-fiber, leading to the sensation of pain. The CGRP receptor activates adenylate cyclase, which leads to an increase in cyclic adenosine monophosphate (cAMP). We hypothesize that cAMP activates the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, triggering an action potential sensed as pain. The mechanisms behind migraine pain on a molecular level, particularly their importance to cAMP, provide clues to potential new anti-migraine targets. In this article we focus on the development of targets related to the CGRP system, and further include novel targets such as the pituitary adenylate cyclase-activating peptide (PACAP) system, the serotonin 5-HT1F receptor, purinergic receptors, HCN channels, adenosine triphosphate-sensitive potassium channels (KATP), and the glutaminergic system.

Original languageEnglish
JournalCNS Drugs
Volume33
Issue number6
Pages (from-to)525-537
Number of pages13
ISSN1172-7047
DOIs
Publication statusPublished - 2019

ID: 57158518