20 Chapter 1 even higher plasma CGRP levels.35 A recent study on menstrual migraine suggested that CGRP concentrations (in serum and tear fluid) in women with migraine during menstruation are higher compared to those in women without migraine.36 However, it is important to note that there are both peripheral and cranial levels of CGRP, which presents some challenges in measuring CGRP. Interestingly, migraine with aura seems to be differentially affected by sex hormones compared to migraine without aura (Figure 3). In contrast to migraine without aura, it is hypothesized that increased estradiol levels during pregnancy and breastfeeding may increase the susceptibility to CSD, thereby initiating or exacerbating migraine attacks with aura.37-39 Studies in CACNA1A knock-in migraine mouse models have shown that female mice exhibit higher susceptibility to CSD compared to males.37, 40 This sex difference was eliminated after ovariectomy in female mice and partially reappeared following treatment with 17β-estradiol.37 Similar findings have been observed in other studies with rodents.39, 41, 42 APPROACHES TO TREATING (MENSTRUAL) MIGRAINE Acute treatment Paracetamol or an Non Steroid Anti Inflammatory Drug (NSAID) in combination with an antiemetic (metoclopramide or domperidone) is the first step. There is no clear benefit of opioids.43 If non-migraine-specific attack medication is ineffective, the next step is acute migraine-specific medication. Triptans are agonists of 5-hydroxytryptamine (5-HT; serotonin) receptors, binding to 5-HT1B and 5-HT1D receptors and some also to the 5-HT1F receptor. The 5-HT1B receptors are responsible for vasoconstriction. In addition, triptans induce central and peripheral inhibition of the trigemino-vascular system, where 5-HT1D and 5-HT1F receptors appear to play an important role. Lasmiditan is a selective 5-HT1F receptor agonist (ditan), and therefore has no vasoconstrictive effects. This is seen as an advantage over triptans, which have a (relative) contraindication in patients with a (severe) CVD risk profile. Lasmiditan demonstrates similar efficacy to triptans; however, its side-effect profile, including dizziness and drowsiness, keeps triptans the preferred choice.44 Among triptans, sumatriptan is also available as a subcutaneous injection, with higher bioavailability.45 It is recommended for a patient to treat at least three attacks with a medication before evaluating its effectiveness. If there is no response during an attack, repeated dosing of a triptan or ditan is not useful, as central sensitization occurs, with activation of second- and third-order neurons in the brainstem and thalamus.46 The timing of
RkJQdWJsaXNoZXIy MjY0ODMw