Discussion
migraine, flushing and heart rate increase, migraine-related disability, headache
MIGRAINE, VASODILATION
Mechanism-specific migraine preventive therapy can reduce frequency and severity of migraine attacks and improve migraine-related disability [Endogenous PACAP plays a role in the regulation of cephalic haemodynamics and is present in perivascular parasympathetic and trigeminal afferent fibers [The PAC1 receptor has previously been suggested as a potential target for treating migraine, inhibiting a key part of the PACAP signalling pathway, since PACAP38 has high affinity on this receptor [Lu AG09222—which in this study prevents PACAP38-induced vasodilatory responses and headache, thereby confirming target engagement—is not dependent on receptors but instead binds and neutralizes the PACAP ligand; therefore, by inhibiting PACAP from binding to its target receptors (PAC1, VPAC1 and VPAC2), the PACAP signalling cascade may be prevented from initiating any physiological responses [VIP infusion induced a short-lived vasodilation of STA, facial flushing and heart rate increase, compared to saline, in the placebo group. This is consistent with previous findings of VIP-induced cephalic vasodilation in healthy volunteers [