Ghanizada H, Al-Karagholi MAM, Arngrim N, et al. - The headache preventive effect of sumatriptan and ketorolac on pituitary adenylate cyclase-activating polypeptide-38 (PACAP38)-induced headache was in healthy volunteers was investigated. Further, an exploration was conducted concerning the contribution of vascular mechanisms to PACAP38-induced headache using high-resolution magnetic resonance angiography. Researchers divided 34 healthy volunteers in two groups (A and B) and provided them an infusion of PACAP38 (10 picomol/kg/min) over 20 min. Pretreatment with intravenous sumatriptan (4 mg) or ketorolac (30 mg) 20 min before infusion of PACAP38 was performed in group A. In group B, sumatriptan or ketorolac was infused as posttreatment 90 min after infusion of PACAP38. Outcomes revealed higher efficacy of posttreatment with ketorolac vs sumatriptan in attenuating PACAP38-induced headache. Ketorolac exerted its impact without altering PACAP38-induced arterial dilation, whereas sumatriptan posttreatment reduced PACAP38-induced dilation of MMA and STA. Pretreatment with sumatriptan reduced PACAP38-induced headache without altering PACAP38-induced arterial dilation. Based on these findings, they suggest that in healthy volunteers, ketorolac and sumatriptan attenuated PACAP38-induced headache without vascular effects.