TY - JOUR

T1 - Headache provocation by nitric oxide in men who have never experienced a headache

AU - Olofsson, Isa Amalie

AU - Falkenberg, Katrine

AU - Olesen, Jes

AU - Hansen, Thomas Folkmann

N1 - Publisher Copyright: © International Headache Society 2021.

PY - 2022

Y1 - 2022

N2 - Introduction: In the general population 4% have never experienced a headache. Freedom from headache could be due to distinctive protective mechanisms or a lack of environmental risk factors for headache. Isosorbide-5-mononitrate is an organic nitrate which in the body is metabolised to nitric oxide. The nitric oxide pathway plays a crucial role in the primary headaches. We hypothesized that people who are free from headache are protected by distinctive mechanisms in the nitric oxide pathway. Methods: We performed an observer blinded case-control study using nitric oxide to provoke a headache. 32 headache free male participants and 26 randomly selected male controls received 60 mg Isosorbide-5-mononitrate orally on the study day. Participants fill out a headache diary with headache intensity and characteristics until 12 hours after administration of Isosorbide-5-mononitrate. Primary endpoint were areas under the curve of headache intensity score. Results: All 58 participants completed the study. There was no significant difference in headache incidence, headache intensity score or migraine-like attack between headache free participants and controls. Conclusion: We show that men who have never experienced a headache develop a headache when provoked with Isosorbide-5-mononitrate. This indicates that freedom from headache in men is not related to the nitric oxide pathway which is involved in the primary headache disorders.

AB - Introduction: In the general population 4% have never experienced a headache. Freedom from headache could be due to distinctive protective mechanisms or a lack of environmental risk factors for headache. Isosorbide-5-mononitrate is an organic nitrate which in the body is metabolised to nitric oxide. The nitric oxide pathway plays a crucial role in the primary headaches. We hypothesized that people who are free from headache are protected by distinctive mechanisms in the nitric oxide pathway. Methods: We performed an observer blinded case-control study using nitric oxide to provoke a headache. 32 headache free male participants and 26 randomly selected male controls received 60 mg Isosorbide-5-mononitrate orally on the study day. Participants fill out a headache diary with headache intensity and characteristics until 12 hours after administration of Isosorbide-5-mononitrate. Primary endpoint were areas under the curve of headache intensity score. Results: All 58 participants completed the study. There was no significant difference in headache incidence, headache intensity score or migraine-like attack between headache free participants and controls. Conclusion: We show that men who have never experienced a headache develop a headache when provoked with Isosorbide-5-mononitrate. This indicates that freedom from headache in men is not related to the nitric oxide pathway which is involved in the primary headache disorders.

KW - isosorbide-5-mononitrate

KW - migraine

KW - never had headache

KW - pathway

KW - protective mechanisms

KW - Provocation study

U2 - 10.1177/03331024211060002

DO - 10.1177/03331024211060002

M3 - Journal article

C2 - 34875880

AN - SCOPUS:85122013902

VL - 42

SP - 598

EP - 607

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 7

ER -