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 HeadacheDisorders, 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-specificactivities/procedures

Exclusion Criteria:

• > 1 mild traumatic injury to the head
• History of any primary or secondary headache disorder prior to mild traumatic injuryto 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, wouldpose a risk to subject safety or interfere with study evaluation, procedures orcompletion
• The subject is at risk of self-harm or harm to others as evidenced by past suicidalbehavior
• Female subjects of childbearing potential with a positive pregnancy test during anystudy 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 2months prior to study inclusion
• Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusionstart
• Baseline headache intensity of >3 on an 11-point numeric rating scale (0 being noheadache, 10 being the worst imaginable headache)
• Baseline headache with migraine-like features or self-reported baseline headache thatmimics the subjects' usual headache with migraine-like features