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.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
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 - PACAP isoforms
KW - headache
KW - mast cell degranulation
KW - serotonin
KW - triptans
UR - http://www.scopus.com/inward/record.url?scp=85100974420&partnerID=8YFLogxK
U2 - 10.1177/0333102420975395
DO - 10.1177/0333102420975395
M3 - Journal article
C2 - 33567890
VL - 41
SP - 731
EP - 748
JO - Cephalalgia
JF - Cephalalgia
SN - 0333-1024
IS - 6
ER -