Sir,
Thank you for sending along correspondence with regard to a recent review.[1] I am grateful for your correspondents’ interest. They make three points:
They comment that citation of data from regional cerebral blood-flow studies[2] to demonstrate a disconnection between migraine pain and vasodilation is insufficient. I would agree. In a wide-reaching review sometimes not all data is cited. It is clear from other work from the same group that superficial temporal artery changes are not seen in migraine triggered by sildenafil,[3] among other examples one could adduce to this point
With regard to magnetic resonance angiography (MRA) work that does not demonstrate any change in extracranial vessel diameter in migraine,[4] the argument regarding vessel size is somewhat circular. While it is possible smaller vessels are the generator of pain; that has not been demonstrated and directly opposes all the more recent pharmacological data. If small vessels are important why does the non-vascular ditan class work?[5,6]
Your correspondent regards the claim that gepants are without vascular effects as a serious misrepresentation. As your correspondent admits olcegepant is not a vasoconstrictor.[7] The statement made was that olcegepant has no vascular action, not that it stops calcitonin gene-related peptide (CGRP) having vasodilation. Nothing about olcegepant was misrepresented. Your correspondent tendentiously pursues vasodilation with a single example, while ignoring that the gepant data sits with the entirety of the clinical trial literature, conveniently ignoring the ditan data cited above or indeed simple things, such as the data on intravenous aspirin in migraine,[8] again as a non-vascular acute treatment.
May I add on a personal note, whatever reason some may have for developing CGRP receptor antagonists, I can assure you that the first rationale was to look at CGRP release in terms neural mechanisms.[9,10] Migraine is a brain disorder;[11] the sooner the organ of the disorder receives full focus, the nearer we come to both enhanced understanding and better therapies.
References
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