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2239438 
Journal Article 
Nitric oxide-induced headache in patients with chronic tension-type headache 
Ashina, M; Bendtsen, L; Jensen, R; Olesen, J 
2000 
Yes 
Brain
ISSN: 0006-8950
EISSN: 1460-2156 
123 ( Pt 9) 
1830-1837 
English 
10960046 
WOS:000089070100005 
An experimental model of headache offers unique possibilities to study the mechanisms responsible for head pain. Using the glyceryl trinitrate [GTN; nitric oxide (NO) donor] model of experimental headache, we studied the intensity, quality and time profile of headache after infusion of GTN in 16 patients with chronic tension-type headache and in 16 healthy controls. Subjects were randomized to receive intravenous infusion of GTN (0.5 microg/kg per minute for 20 min) or placebo on two headache-free days separated by at least 1 week. Headache intensity was measured on a 10-point verbal rating scale during 2 h of observation and for the next 10 h after discharge from hospital. The primary endpoints were the difference between the area under the curve (AUC-intensities x duration) for headache recorded on the day of GTN treatment and on the day of placebo treatment in patients, and in patients and controls on the days of GTN treatment. In patients, the AUC on a GTN day [2221 (1572-3704); median with quartiles in parentheses], was significantly greater than on a placebo day [730 (60-1678), P: = 0. 008]. On the GTN day, the AUC in patients [2221 (1572-3704)] was significantly higher than in controls [43 (0-972), P: = 0.0001]. In patients, peak pain intensity occurred 8 h after infusion of GTN, whereas in controls it occurred 20 min after the start of infusion. The present study demonstrates that an NO-induced biphasic response with an immediate and a delayed headache is common to chronic tension-type headache and migraine. Furthermore, the NO-induced delayed headache has the characteristics of the primary headache disorder. This suggests that NO contributes to the mechanisms of several types of primary headaches and that NO-related central sensitization may be an important common denominator in the pain mechanisms of primary headaches. 
tension-type headache; nitric oxide; central sensitization; glyceryl trinitrate; primary headaches