Hypersensitivity to opening of ATP-sensitive potassium channels in post-traumatic headache

To investigate whether levcromakalim (a K_ATP channel opener) induces migraine-like headache in people with persistent post-traumatic headache who had no known history of migraine.

In a randomized, double-blind, placebo-controlled, 2-way crossover trial, participants were randomly assigned to receive a 20-minute continuous intravenous infusion of levcromakalim (50 µg/mL) or placebo (isotonic saline) on two separate experimental days with a 1-week wash-out period in between. The primary endpoint was the difference in incidence of migraine-like headache between levcromakalim and placebo during a 12-hour observational period after infusion start. The secondary endpoint was the difference in area under the curve for baseline-corrected median headache intensity scores between levcromakalim and placebo during the 12-hour observational period.

A total of 21 participants with persistent post-traumatic headache were randomized and completed the trial. During the 12-hour observational period, 12 (57%) of 21 participants reported experiencing migraine-like headache following the levcromakalim infusion, compared with three after placebo (P = 0.013). Moreover, the baseline-corrected median headache intensity scores were higher following the levcromakalim infusion than after placebo (P = 0.003).

Our findings suggest that K_ATP channels play an important role in the pathogenesis of migraine-like headache in people with persistent post-traumatic headache. This implies that K_ATP channel blockers might represent a promising avenue for drug development. Further research is warranted to explore the potential therapeutic benefits of K_ATP channel blockers in managing post-traumatic headache.Trial Registration: ClinicalTrials.gov Identifier: NCT05243953.