Skip to main content


Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Chronic headache and nitric oxide inhibitors


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.

Author information

Additional information

Received: 19 February 2001 / Accepted: 11 April 2001

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ashina, M., Bendtsen, L. Chronic headache and nitric oxide inhibitors. J Headache Pain 2, 21–24 (2001).

Download citation

  • Key words Chronic headache
  • Nitric oxide inhibitors


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Please note that comments may be removed without notice if they are flagged by another user or do not comply with our community guidelines.