Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache. / Ghanizada, Hashmat; Al-Karagholi, Mohammad Al Mahdi; Arngrim, Nanna; Mørch-Rasmussen, Mette; Metcalf-Clausen, Matias; Larsson, Henrik Bo Wiberg; Amin, Faisal Mohammad; Ashina, Messoud.
I: Journal of Headache and Pain, Bind 21, Nr. 1, 19, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache
AU - Ghanizada, Hashmat
AU - Al-Karagholi, Mohammad Al Mahdi
AU - Arngrim, Nanna
AU - Mørch-Rasmussen, Mette
AU - Metcalf-Clausen, Matias
AU - Larsson, Henrik Bo Wiberg
AU - Amin, Faisal Mohammad
AU - Ashina, Messoud
PY - 2020
Y1 - 2020
N2 - 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).
AB - 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).
KW - Arterial dilation
KW - Headache
KW - Mast cell degranulation
KW - MRA
KW - Neuroinflammation
KW - NSAIDs
KW - PACAP38
KW - Pain
KW - Plasma protein extravasation
U2 - 10.1186/s10194-020-01089-3
DO - 10.1186/s10194-020-01089-3
M3 - Journal article
C2 - 32093617
AN - SCOPUS:85080944584
VL - 21
JO - Journal of Headache and Pain
JF - Journal of Headache and Pain
SN - 1129-2369
IS - 1
M1 - 19
ER -
ID: 250208548