Nitric oxide-induced headache in patients with chronic tension-type headache

An experimental model of headache offers unique possibilities to study the mechanisms responsible for head pain, Using the glyceryl trinitrate [GTN; n itric oxide (NO) donor] model of experimental headache, we studied the inte nsity, quality and time profile of headache after infusion of GTN in 16 pat ients with chronic tension-type headache and in 16 healthy controls. Subjec ts were randomized to receive intravenous infusion of GTN (0.5 mu g/kg per minute for 20 min) or placebo on two headache-free days separated by at lea st 1 week, Headache intensity was measured on a 10-point verbal rating scal e during 2 h of observation and for the next 10 h after discharge from hosp ital, 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 da y [2221 (1572-3704); median with quartiles in parentheses], was significant ly 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 c ontrols [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 th e start of infusion. The present study demonstrates that an NO-induced biph asic response with an immediate and a delayed headache is common to chronic tension-type headache and migraine. Furthermore, the NO-induced delayed he adache has the characteristics of the primary headache disorder. This sugge sts that NO contributes to the mechanisms of several types of primary heada ches and that NO-related central sensitization may be an important common d enominator in the pain mechanisms of primary headaches.