Hypersensitivity to Phosphodiesterase 5 Inhibition in Post-Traumatic Headache

Inclusion Criteria: Age 18 to 65 years of age upon entry into screening History of persistent headache attributed to mild traumatic injury to the head for ≥ 12 months and in accordance with the International Classification of Headache Disorders, 3rd Edition (ICHD-3) ≥ 4 monthly headache days on average across the 3 months prior to screening Provision of informed consent prior to initiation of any study-specific activities/procedures Exclusion Criteria: > 1 mild traumatic injury to the head History of any primary or secondary headache disorder prior to mild traumatic injury to the head (except for infrequent episodic tension-type headache) History of moderate or severe injury to the head History of whiplash injury History of craniotomy History or evidence of any other clinically significant disorder, condition or disease (except for those outlined above) than, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior Female subjects of childbearing potential with a positive pregnancy test during any study visit Cardiovascular disease of any kind, including cerebrovascular diseases Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg) Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start Baseline headache intensity of >3 on an 11-point numeric rating scale (0 being no headache, 10 being the worst imaginable headache) Baseline headache with migraine-like features or self-reported baseline headache that mimics the subjects' usual headache with migraine-like features