TY - JOUR

T1 - Early treatment with sumatriptan prevents PACAP38-induced migraine

T2 - A randomised clinical trial

AU - Wienholtz, Nita Katarina Frifelt

AU - Christensen, Casper Emil

AU - Zhang, Ditte Georgina

AU - Coskun, Hande

AU - Ghanizada, Hashmat

AU - Al-Karagholi, Mohammad Al Mahdi

AU - Hannibal, Jens

AU - Egeberg, Alexander

AU - Thyssen, Jacob P.

AU - Ashina, Messoud

N1 - Publisher Copyright: © International Headache Society 2021.

PY - 2021

Y1 - 2021

N2 - Objective: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. Results: Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo (p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) (p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo (p < 0.001). Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system. Trial Registration: ClinicalTrials.gov (NCT03881644).

AB - Objective: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. Results: Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo (p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) (p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo (p < 0.001). Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system. Trial Registration: ClinicalTrials.gov (NCT03881644).

KW - Blood vessels

KW - headache

KW - mast cell degranulation

KW - PACAP isoforms

KW - serotonin

KW - triptans

U2 - 10.1177/0333102420975395

DO - 10.1177/0333102420975395

M3 - Journal article

C2 - 33567890

AN - SCOPUS:85100974420

VL - 41

SP - 731

EP - 748

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 6

ER -