Effect of inhibition of nitric oxide synthase on chronic tension-type headache: a randomised crossover trial

Background Studies in animals have shown that nitric oxide plays an importa nt part in central sensitisation and that inhibitors of nitric oxide syntha se (NOS) decrease sensitisation in models of persistent pain. The efficacy of inhibitors of NOS has not been tested in patients with tension-type chro nic headache. We aimed to show whether NG-monomethyl-L-arginine hydrochlori de (L-NM MA), an inhibitor of NOS, is effective in relieving pain ip such p atients. Methods We undertook a randomised double-blind, crossover trial of 16 patie nts with chronic-tension-type headache. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 wee k in a randomised order. Headache intensity was measured on a 100 mm visual analogue scale, and on a verbal rating scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. The primary endpoint was reduct ion of pain intensity on the visual analogue scale by the active treatment compared with placebo. Findings L-NMMA reduced pain intensity on the visual analogue scale signifi cantly more than placebo: 120 min after start of treatment, the mean pain s core was decreased from 49 to 33 with L-NMMA and from 44 to 40 with placebo (p = 0.01). Pain intensity on the verbal rating scale was also significant ly lower for treatment with L-NMMA than for treatment with placebo (p = 0.0 2). Interpretation Inhibition of NOS had an analgesic effect in chronic tension -type headache. Further tests are required before clinical application.