Hypersensitivity to BK_Ca channel opening in persistent post-traumatic headache.

IF 7.3 1区医学 Q1 CLINICAL NEUROLOGY Journal of Headache and Pain Pub Date : 2024-06-18 DOI:10.1186/s10194-024-01808-0

Haidar M Al-Khazali, Rune H Christensen, David W Dodick, Basit Ali Chaudhry, Anna G Melchior, Rami Burstein, Håkan Ashina

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Abstract

Background: Large conductance calcium-activated potassium (BK_Ca) 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_Ca 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 BK_Ca channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BK_Ca 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_Ca channel blockers in managing PPTH.

Clinicaltrials:

Gov identifier: NCT05378074.

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创伤后持续性头痛对 BKCa 通道开放的超敏反应

背景：大电导钙激活钾（BKCa）通道与偏头痛的神经生物学基础有关。考虑到偏头痛和持续性创伤后头痛（PPTH）之间的临床相似性，我们旨在研究 MaxiPost（一种 BKCa 通道开放剂）是否能诱发 PPTH 患者的偏头痛样头痛：这是一项随机双盲、安慰剂对照、双向交叉研究，研究时间为2023年9月至2023年12月。符合条件的参与者均为轻度脑外伤后患有 PPTH 的成年人，且自述无偏头痛病史。随机参与者在20分钟内接受单剂量MaxiPost（0.05毫克/分钟）或安慰剂（等渗盐水）静脉注射。两次实验至少间隔一周，以避免潜在的带入效应。主要终点是与安慰剂相比，MaxiPost 在用药后 12 小时内诱发偏头痛样头痛。次要终点是在相同的12小时观察期内，MaxiPost与安慰剂的头痛强度评分曲线下面积（AUC）值：21名患有PPTH的成年参与者（包括14名女性和7名男性）参加并完成了两次实验。输注MaxiPost后，21名参与者中有11人（52%）出现类似偏头痛的症状，而输注安慰剂后有4人（19%）出现类似偏头痛的症状（P = .02）。此外，以AUC值表示的头痛强度评分中值在MaxiPost治疗后高于安慰剂治疗后（P < .001）：我们的研究结果表明，BKCa 通道开放可引起 PPTH 患者偏头痛样头痛。结论：我们的研究结果表明，BKCa 通道开放可引起 PPTH 患者偏头痛样头痛，因此，对 BKCa 通道进行药物阻断可能是药物研发的一个新途径。然而，还需要进行更多的研究来证实这些见解，并探索 BKCa 通道阻滞剂在治疗 PPTH 方面的治疗前景：Gov 标识符：NCT05378074。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Headache and Pain 医学-临床神经学

CiteScore

11.80

自引率

13.50%

发文量

143

审稿时长

6-12 weeks

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.