Brain : a journal of neurology
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Randomized Controlled Trial Multicenter Study Clinical Trial
Possible mechanisms of action of nitric oxide synthase inhibitors in chronic tension-type headache.
It has been demonstrated recently that nitric oxide synthase (NOS) inhibition 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 inhibitor, L-N(G) methyl arginine hydrochloride (L-NMMA), on two of the most prominent features of chronic tension-type headache, i.e. increased muscle hardness and increased myofascial tenderness. In a double blind, crossover designed trial, 16 patients with chronic tension-type headache were randomized to receive intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week. ⋯ 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; tenderness, 15 +/- 11 and 14 +/- 11, respectively, after treatment with L-NMMA (P < 0.05 and P < 0.01, respectively), while there was no significant reduction 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 treatment with L-NMMA. Since increased muscle hardness in patients with chronic tension-type headache may reflect sensitization of second order neurons due to prolonged nociceptive input from myofascial tissues, we suggest that the decrease in muscle hardness following treatment with L-NMMA may be caused by reduction of central sensitization.