Mohammad Al-Mahdi Al-Karagholi1, Hashmat Ghanizada2, Jakob M Hansen1, Lene T Skovgaard3, Jes Olesen1,2, Henrik B W Larsson4, Faisal M Amin1, Messoud Ashina1. 1. Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 2. Glostrup Research Park, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 3. Department of Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND:ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migraine patients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown. OBJECTIVE: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relationship between the middle meningeal artery (MMA) dilation and headache. METHODS: In a double-blind, randomized, placebo-controlled study, 20 healthy volunteers were scanned at the baseline and repeatedly after infusion of levcromakalim (n = 14) and placebo (n = 6). All participants received a subcutaneous injection of sumatriptan 6 mg before the last scanning. RESULTS: The MMA circumference was significantly larger after levcromakalim compared with placebo (P < .0001). The MMA dilation lasted over 5 hours during observational period. We found a significant association between headache and MMA dilation (P < .0001). The superficial temporal artery (STA) circumference was significantly larger after levcromakalim compared with placebo (P = .03) over the initial period (110 minutes). Over the entire observational period, there was no difference in circumference of the STA and the middle cerebral artery (MCA) between levcromakalim and placebo. CONCLUSION:Levcromakalim dilated the MMA but not MCA. The MMA dilation was associated with headache. Future studies should investigate whether opening of KATP channels can activate and sensitize the perivascular nociceptors.
RCT Entities:
BACKGROUND:ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migrainepatients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown. OBJECTIVE: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relationship between the middle meningeal artery (MMA) dilation and headache. METHODS: In a double-blind, randomized, placebo-controlled study, 20 healthy volunteers were scanned at the baseline and repeatedly after infusion of levcromakalim (n = 14) and placebo (n = 6). All participants received a subcutaneous injection of sumatriptan 6 mg before the last scanning. RESULTS: The MMA circumference was significantly larger after levcromakalim compared with placebo (P < .0001). The MMA dilation lasted over 5 hours during observational period. We found a significant association between headache and MMA dilation (P < .0001). The superficial temporal artery (STA) circumference was significantly larger after levcromakalim compared with placebo (P = .03) over the initial period (110 minutes). Over the entire observational period, there was no difference in circumference of the STA and the middle cerebral artery (MCA) between levcromakalim and placebo. CONCLUSION:Levcromakalim dilated the MMA but not MCA. The MMA dilation was associated with headache. Future studies should investigate whether opening of KATP channels can activate and sensitize the perivascular nociceptors.
Authors: Hashmat Ghanizada; Mohammad Al-Mahdi Al-Karagholi; Christopher S Walker; Nanna Arngrim; Tayla Rees; Jakeb Petersen; Andrew Siow; Mette Mørch-Rasmussen; Sheryl Tan; Simon J O'Carroll; Paul Harris; Lene Theil Skovgaard; Niklas Rye Jørgensen; Margaret Brimble; Jayme S Waite; Brandon J Rea; Levi P Sowers; Andrew F Russo; Debbie L Hay; Messoud Ashina Journal: Ann Neurol Date: 2021-04-08 Impact factor: 11.274