Nitric oxide pathway and response to nitroglycerin in cluster headache patients: Plasma nitrite and citrulline levels

A. Costa, S. Ravaglia, G. Sances, F. Antonaci, E. Pucci, G. Nappi

Research output: Contribution to journalArticlepeer-review


Nitric oxide (NO) may participate in the mechanisms underlying vascular headaches, such as migraine and cluster headache (CH), by triggering neurogenic inflammation and activation of fibres conveying nociceptive inputs to the trigeminal ganglion. Similarly to migraine, the administration of the NO donor glyceryltrinitrate (GTN) to CH patients is a known model of inducing spontaneous-like attacks. We carried out a GTN test (0.9 mg, sublingually) in 18 patients with episodic CH in active phase and 12 controls. The plasma levels of NO metabolite nitrites (NO2 -), after conversion of nitrates to NO2 -, were measured spectrophoto-metrically at baseline, at the maximum intensity of the induced response (or 45 min after GTN in controls), and 120 min after GTN administration. The basal plasma levels of L-citrulline were also assayed in patients and controls using high-performance liquid chromatography. Basal NO2 - levels, similar in GTN-responsive patients and controls (48.3 ± 10.6 and 44.6 ± 9.5 μmol/1, respectively) were found to be increased significantly at pain peak in patients (76.1 ± 10.2 μmol/1) and after 45 min in controls (78.2 ± 9.6 μmol/1) (P <0.01 vs. respective baseline values), but not after 120 min, without differences between groups. L-citrulline levels in basal conditions showed no differences between groups (patients 64.8 ± 11.7, controls 67.3 ±10.8 μmol/1). These data do not support the presence of a basal hyperactivity of the L-arginine-NO pathway in CH patients. Increased NO production may be of importance in the mechanisms leading to CH attacks, but other factors are likely to render CH patients hyperresponsive to NO, and ultimately to cause the occurrence of pain and associated features.

Original languageEnglish
Pages (from-to)407-413
Number of pages7
Issue number6
Publication statusPublished - Jul 2003


  • Citrulline
  • Cluster headache
  • Glyceryltrinitrate
  • Nitric oxide
  • Nitrites
  • Trigeminovascular system

ASJC Scopus subject areas

  • Clinical Neurology


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