VIPR2 and Headache: Nonetheless, the PACAP signalling pathway is of interest as both the ligand and its receptors are expressed within the trigeminovascular system.5 In humans, PACAP binds to three different receptors (VPAC1, VPAC2 and PAC1), and experimental data have shown that activation of these receptors can increase intracellular levels of cAMP.5 Furthermore, a recent clinical trial demonstrated that Lu AG09222, an anti-PACAP mAb, was effective in inhibiting PACAP38-induced cephalic vasodilation and reducing concomitant headache in healthy volunteers.28