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- Title
Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache.
- Authors
Ghanizada, Hashmat; Al-Karagholi, Mohammad Al-Mahdi; Arngrim, Nanna; Mørch-Rasmussen, Mette; Metcalf-Clausen, Matias; Larsson, Henrik Bo Wiberg; Amin, Faisal Mohammad; Ashina, Messoud
- Abstract
Background: Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces headache in healthy volunteers but the precise mechanisms by which PACAP38 leads to headache are unclear. We investigated the headache preventive effect of sumatriptan and ketorolac on PACAP38-induced headache in healthy volunteers. In addition, we explored contribution of vascular mechanisms to PACAP38-induced headache using high resolution magnetic resonance angiography. Methods: Thirty-four healthy volunteers were divided in two groups (A and B) and received infusion of PACAP38 (10 picomol/kg/min) over 20 min. Group A was pretreated with intravenous sumatriptan (4 mg) or ketorolac (30 mg) 20 min before infusion of PACAP38. Group B received infusion of sumatriptan or ketorolac as post-treatment 90 min after infusion of PACAP38. In both experiments, we used a randomized, double-blind, cross-over design. We recorded headache characteristics and circumference of extra-intracerebral arteries. Results: We found no difference in AUC (0–6 h) of PACAP38-induced headache in group A, pretreated with sumatriptan or ketorolac (p = 0.297). There was no difference between sumatriptan and ketorolac in PACAP38-induced circumference change (AUCBaseline-110 min) of MMA (p = 0.227), STA (p = 0.795) and MCA (p = 0.356). In group B, post-treatment with ketorolac reduced PACAP38-headache compared to sumatriptan (p < 0.001). Post-treatment with sumatriptan significantly reduced the circumference of STA (p = 0.039) and MMA (p = 0.015) but not of MCA (p = 0.981) compared to ketorolac. In an explorative analysis, we found that pre-treatment with sumatriptan reduced PACAP38-induced headache compared to no treatment (AUC0-90min). Conclusions: Post-treatment with ketorolac was more effective in attenuating PACAP38-induced headache compared to sumatriptan. Ketorolac exerted its effect without affecting PACAP38-induced arterial dilation, whereas sumatriptan post-treatment attenuated PACAP38-induced dilation of MMA and STA. Pre-treatment with sumatriptan attenuated PACAP38-induced headache without affecting PACAP38-induced arterial dilation. Our findings suggest that ketorolac and sumatriptan attenuated PACAP38-induced headache in healthy volunteers without vascular effects. Trial registration: Clinicaltrials.gov (NCT03585894). Registered 13 July 2018,
- Subjects
VASODILATION; CARDIOVASCULAR disease diagnosis; CEREBRAL arteries; CROSSOVER trials; HEADACHE; INTRAVENOUS therapy; MENINGEAL artery; NEUROPEPTIDES; SUMATRIPTAN; KETOROLAC; RANDOMIZED controlled trials; TREATMENT effectiveness; BLIND experiment; TREATMENT duration; TROMETHAMINE; MAGNETIC resonance angiography; TEMPORAL arteries
- Publication
Journal of Headache & Pain, 2020, Vol 21, Issue 1, p1
- ISSN
1129-2369
- Publication type
Article
- DOI
10.1186/s10194-020-01089-3