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Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine

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@article{001eb8f1d5534c34b3eb8139c17b5939,
title = "Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine",
abstract = "ABSTRACT: Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six patients with migraine without aura were randomly allocated to receive an infusion of MaxiPost or placebo on 2 study days separated by at least 1 week. The primary endpoint was the difference in incidence of migraine attacks after MaxiPost compared with placebo. The secondary endpoints were the difference in incidence of headaches and the difference in area under the curve for headache intensity scores (0-12 hours), for middle cerebral artery blood flow velocity (VMCA) (0-2 hours), and for superficial temporal artery and radial artery diameter. Twenty-two patients completed the study. Twenty-one of 22 (95%) developed migraine attacks after MaxiPost compared with none after placebo (P < 0.0001); the difference of incidence is 95% (95% confidence interval 86%-100%). The incidence of headache over the 12-hour observation period was higher after MaxiPost day (n = 22) than after placebo (n = 7) (P < 0.0001). We found a significant increase of VMCA and superficial temporal and radial arteries' diameter. Because BKCa channel opening initiates migraine attacks, we suggest that BKCa channel blockers could be potential candidates for novel antimigraine drugs.",
author = "Al-Karagholi, {Mohammad Al-Mahdi} and Hashmat Ghanizada and {Waldorff Nielsen}, {Cherie Amalie} and Camilla Skandarioon and Josefin Snellman and Cristina Lopez-Lopez and Hansen, {Jakob M{\o}ller} and Messoud Ashina",
note = "Copyright {\textcopyright} 2021 International Association for the Study of Pain.",
year = "2021",
month = oct,
day = "1",
doi = "10.1097/j.pain.0000000000002238",
language = "English",
volume = "162",
pages = "2512--2520",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier BV",
number = "10",

}

RIS

TY - JOUR

T1 - Opening of BKCa channels causes migraine attacks

T2 - a new downstream target for the treatment of migraine

AU - Al-Karagholi, Mohammad Al-Mahdi

AU - Ghanizada, Hashmat

AU - Waldorff Nielsen, Cherie Amalie

AU - Skandarioon, Camilla

AU - Snellman, Josefin

AU - Lopez-Lopez, Cristina

AU - Hansen, Jakob Møller

AU - Ashina, Messoud

N1 - Copyright © 2021 International Association for the Study of Pain.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - ABSTRACT: Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six patients with migraine without aura were randomly allocated to receive an infusion of MaxiPost or placebo on 2 study days separated by at least 1 week. The primary endpoint was the difference in incidence of migraine attacks after MaxiPost compared with placebo. The secondary endpoints were the difference in incidence of headaches and the difference in area under the curve for headache intensity scores (0-12 hours), for middle cerebral artery blood flow velocity (VMCA) (0-2 hours), and for superficial temporal artery and radial artery diameter. Twenty-two patients completed the study. Twenty-one of 22 (95%) developed migraine attacks after MaxiPost compared with none after placebo (P < 0.0001); the difference of incidence is 95% (95% confidence interval 86%-100%). The incidence of headache over the 12-hour observation period was higher after MaxiPost day (n = 22) than after placebo (n = 7) (P < 0.0001). We found a significant increase of VMCA and superficial temporal and radial arteries' diameter. Because BKCa channel opening initiates migraine attacks, we suggest that BKCa channel blockers could be potential candidates for novel antimigraine drugs.

AB - ABSTRACT: Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six patients with migraine without aura were randomly allocated to receive an infusion of MaxiPost or placebo on 2 study days separated by at least 1 week. The primary endpoint was the difference in incidence of migraine attacks after MaxiPost compared with placebo. The secondary endpoints were the difference in incidence of headaches and the difference in area under the curve for headache intensity scores (0-12 hours), for middle cerebral artery blood flow velocity (VMCA) (0-2 hours), and for superficial temporal artery and radial artery diameter. Twenty-two patients completed the study. Twenty-one of 22 (95%) developed migraine attacks after MaxiPost compared with none after placebo (P < 0.0001); the difference of incidence is 95% (95% confidence interval 86%-100%). The incidence of headache over the 12-hour observation period was higher after MaxiPost day (n = 22) than after placebo (n = 7) (P < 0.0001). We found a significant increase of VMCA and superficial temporal and radial arteries' diameter. Because BKCa channel opening initiates migraine attacks, we suggest that BKCa channel blockers could be potential candidates for novel antimigraine drugs.

UR - http://www.scopus.com/inward/record.url?scp=85106457630&partnerID=8YFLogxK

U2 - 10.1097/j.pain.0000000000002238

DO - 10.1097/j.pain.0000000000002238

M3 - Journal article

C2 - 34252916

VL - 162

SP - 2512

EP - 2520

JO - Pain

JF - Pain

SN - 0304-3959

IS - 10

ER -

ID: 66964894