The Journal of Headache and Pain

"European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"

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Open Access

Chronic headache and nitric oxide inhibitors

  • Messoud Ashina and
  • Lars Bendtsen
The Journal of Headache and PainOfficial Journal of the Italian Society for the Study of Headaches2:10020021.10194


Sensitization of myofascial pain pathways may play an important role in the pathophysiology of chronic headache. Animal studies have shown that sensitization of pain pathways may be caused by associated with activation of neuronal nitric oxide synthase (nNOS) and the generation of nitric oxide (NO).

Furthermore, it has been shown that NOS inhibitors reduce central sensitization in animal models of persistent pain. On the basis of these findings, we investigated the analgesic effect of the NOS inhibitor, N-N G-methyl arginine hydrochloride, and demonstrated that this drug significantly reduced headache as well as myofascial factors in patients with chronic tension-type headache. In addition, we demonstrated that infusion of the NO donor, glyceryl trinitrate, induces headache in these patients, probably by enhancing the sensitizing effect of pre-existing myofascial input. These studies strongly indicate that NO plays a crucial role in the pathophysiology of tension-type headache. We suggested that the analgesic effect of NOS inhibition in patients with chronic tension-type headache is most likely due to reduction of central sensitization at the level of the spinal dorsal horn or trigeminal nucleus, or both. Furthermore, these data suggest that inhibition of NOS may become a novel means of future treatment of chronic headache.

Key words Chronic headacheNitric oxide inhibitors