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

Nitric oxide: emerging implications for headache mechanics


The involvement of nitric oxide (NO) in the pathophysiology of primary headaches was suggested by several authors during the last decade. Migraine, cluster headache, tension headache, and cervicogenic headache have been extensively studied on the basis of NO donor headache pain. Different mechanisms seem to be involved in the generation of pain in these clearly different clinical head pain disorders. NO could control all the mechanisms leading to head pain. In migraine NO is correlated with endothelial activation, in cluster headache with a brainstem unravelling of the on/off regulatory clocks, in cervicogenic headache with a cytokine-dependent pain, and in tension-type headache with a sensitization of pain pathways at the spinal/trigeminal level. The next natural frontier in the study of pain in primary headaches seems to be the functional study of the relationship between NO and the immune regulatory system.

Author information

Additional information

Received: 30 Devember 2000 / Accepted in revised form: 9 April 2001

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zicari, A., Giacovazzo, M. & Martelletti, P. Nitric oxide: emerging implications for headache mechanics. J Headache Pain 2, 67–72 (2001).

Download citation

  • Key words Nitric oxide
  • Migraine
  • Tension-type headache
  • Cerviogenic headache
  • Cluster headache


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.