Calcitonin gene-related peptide antagonism and cluster headache: an emerging new treatment
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Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov. The search term used was “cluster headache and calcitonin gene related peptide” and “primary headaches and calcitonin gene related peptide.” Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play an important role in cluster headache pathophysiology. More refined human studies are warranted with regard to assay validation and using larger sample sizes. The results from RCTs may reveal the therapeutic potential of CGRP monoclonal antibodies and antagonists for cluster headache treatment.
KeywordsCalcitonin gene-related peptide Cluster headache Antagonism Trigeminal system Pathophysiology Pain
HA conducted the literature search. All the authors contributed with data interpretation, drafting, and revision of the manuscript. All the authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
Håkan Ashina has no disclosures. Lawrence Newman has received honoraria for his work as a consultant for Allergan, Amgen, Alder, Avanir, Depomed, E Neura, and Supernus. Sait Ashina received honoraria for lecturing from Allergan and Avanir Pharmaceuticals. Sait Ashina is also a principal investigator for Alder Pharmaceuticals trial NCT02974153.
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