Haidar M Al-Khazali, Rune H Christensen, David W Dodick, Basit Ali Chaudhry, Anna G Melchior, Rami Burstein, Håkan Ashina
{"title":"创伤后持续性头痛对 BKCa 通道开放的超敏反应","authors":"Haidar M Al-Khazali, Rune H Christensen, David W Dodick, Basit Ali Chaudhry, Anna G Melchior, Rami Burstein, Håkan Ashina","doi":"10.1186/s10194-024-01808-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Large conductance calcium-activated potassium (BK<sub>Ca</sub>) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BK<sub>Ca</sub> channel opener) could induce migraine-like headache in persons with PPTH.</p><p><strong>Methods: </strong>This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period.</p><p><strong>Results: </strong>Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001).</p><p><strong>Conclusions: </strong>Our results indicate that BK<sub>Ca</sub> channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BK<sub>Ca</sub> channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BK<sub>Ca</sub> channel blockers in managing PPTH.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT05378074.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":null,"pages":null},"PeriodicalIF":7.3000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186171/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hypersensitivity to BK<sub>Ca</sub> channel opening in persistent post-traumatic headache.\",\"authors\":\"Haidar M Al-Khazali, Rune H Christensen, David W Dodick, Basit Ali Chaudhry, Anna G Melchior, Rami Burstein, Håkan Ashina\",\"doi\":\"10.1186/s10194-024-01808-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Large conductance calcium-activated potassium (BK<sub>Ca</sub>) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BK<sub>Ca</sub> channel opener) could induce migraine-like headache in persons with PPTH.</p><p><strong>Methods: </strong>This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period.</p><p><strong>Results: </strong>Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001).</p><p><strong>Conclusions: </strong>Our results indicate that BK<sub>Ca</sub> channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BK<sub>Ca</sub> channels might present a novel avenue for drug discovery. 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Hypersensitivity to BKCa channel opening in persistent post-traumatic headache.
Background: Large conductance calcium-activated potassium (BKCa) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could induce migraine-like headache in persons with PPTH.
Methods: This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period.
Results: Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001).
Conclusions: Our results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BKCa channel blockers in managing PPTH.
期刊介绍：
The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data.
With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.
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