Possible mechanisms of action of nitric oxide synthase inhibitors in chronic tension-type headache

It has been demonstrated recently that nitric oxide synthase (NOS) inhibiti on has an analgesic effect in patients with chronic tension-type headache. The aim of the present study was to investigate the influence of the NOS in hibitor, L-N-G methyl arginine hydrochloride (L-NMMA), on two of the most p rominent features of chronic tension-type headache, i.e. increased muscle h ardness and increased myofascial tenderness. In a double blind, crossover d esigned trial, 16 patients with chronic tension-type headache were randomiz ed to receive intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days s eparated by at least 1 week. Muscle hardness of the trapezius muscle was me asured with a hardness meter. Myofascial tenderness in the pericranial regi on was evaluated by manual palpation with standardized and validated method ology. All parameters were recorded at baseline and at 60 and 120 min after start of infusion, Compared with baseline, muscle hardness, 107 +/- 17 kPa /cm and tenderness, 18 +/- 11 were significantly reduced at 60 and 120 min to: hardness, 101 +/- 17 kPa/cm and 101 +/- 17 kPa/cm, respectively; tender ness, 15 +/- 11 and 14 +/- 11, respectively, after treatment with L-NMMA (P < 0.05 and P < 0.01, respectively), while there was no significant reducti on at any time after treatment with the placebo. Compared with the placebo, the summary score of muscle hardness was significantly reduced (P = 0.04), while tenderness showed a non-significant reduction (P = 0.11) following t reatment with L-NMMA. Since increased muscle hardness in patients with chro nic tension-type headache may reflect sensitization of second order neurons due to prolonged nociceptive input from myofascial tissues, we suggest tha t the decrease in muscle hardness following treatment with L-NMMA may be ca used by reduction of central sensitization.