Abstract
Migraine is a neurovascular disorder that is three times more prevalent in women than in men and represents a large socio-economic burden. Therefore, the development of new preventive medications is an urgent matter. Currently, calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal fibres, is an important target for migraine treatment. Accordingly, antibodies directed against CGRP or its receptor, as well as small-molecule CGRP receptor antagonists, have been developed for the prophylactic and acute treatment of migraine. Results from clinical phase III trials show a significant decrease in migraine days and relatively mild side-effects. However, CGRP is not only present in the trigeminal nerve, but it is also abundant in perivascular nerve fibres. Moreover, CGRP levels and hormones vary between sexes and during different life stages, and hormones affect CGRP, with a seemingly greater role for CGRP in females. In this review we discuss whether these aspects could be associated with differences in response and efficacy of drugs interfering with the CGRP pathway. Furthermore, CGRP has been described as playing a protective role in ischemic events, and CGRP seems to play a larger role in cardiac ischemic events in female patients. As cardiovascular risk is increased in female migraine patients and also increases significantly in females after menopause, further research into the risk of blocking CGRP in these patients is needed.
Highlights
A crucial role in the development of a migraine attack is attributed to the activation of the trigeminovascular system [3]
Search terms used to identify literature included: migraine, menopause, pregnancy, cerebrovascular risk, cardiovascular risk, all separately combined with calcitonin gene-related peptide (CGRP)
CGRP has been marked as a specific target for migraine, not all migraine patients benefit from treatment
Summary
It is estimated that 15 % of the world population suffers from migraine, representing a large socioeconomic burden [1]. It is characterized by unilateral pulsating pain of moderate to severe intensity, often aggravated by physical activity and accompanied by nausea, vomiting, photophobia and phonophobia. A crucial role in the development of a migraine attack is attributed to the activation of the trigeminovascular system [3]. This system consists of sensory neurons of the trigeminal nucleus caudalis and the trigeminal ganglion, with the latter innervating cranial blood vessels. Infusion of CGRP in migraine patients induces a migraine-like headache [7]
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