Carbon monoxide inhalation induces headache but no migraine in patients with migraine without aura

Introduction Carbon monoxide is an endogenously produced signaling gasotransmitter known to cause headache and vasodilation. We hypothesized that inhalation of carbon monoxide would induce migraine-like attacks in migraine without aura patients. Methods In a randomized, double-blind, placebo-controlled crossover design, 12 migraine patients were allocated to inhalation of carbon monoxide (carboxyhemoglobin 22%) or placebo on two separate days. Headache and migraine characteristics were recorded during hospital (0-2 hours) and post-hospital (2-13 hours) phases. Results Six patients (50%) developed migraine-like attacks after carbon monoxide compared to two after placebo (16.7%) (p = 0.289). The median time to onset of migraine-like attacks after carbon monoxide inhalation was 7.5 h (range 3-12) compared to 11.5 h (range 11-12) after placebo. Nine out of 12 patients (75%) developed prolonged headache after carbon monoxide. The area under the curve for headache score (0-13 hours) was increased after carbon monoxide compared with placebo (p = 0.033). Conclusion Carbon monoxide inhalation did not provoke more migraine-like attacks in migraine patients compared to placebo, but induced more headache in patients compared to placebo. These data suggest that non-toxic concentrations of carbon monoxide had low potency in migraine induction and that the carbon monoxide inhalation model is not suitable to study migraine.