Nitric Oxide, Endothelin‐1, and Transcranial Doppler in Migraine. Findings in Interictal Conditions and During Migraine Attac

Abstract

The role of vascular phenomena taking place during an attack of migraine are poorly understood. The aim of this study was to measure systemic levels of nitric oxide and endothelin-1, two of the most potent vasoactive mediators known, and to assess vasomotor responses through transcranial Doppler ultrasound monitoring in patients suffering from migraine without aura, both during the headache event and in headache-free periods as well as after pharmacologically induced pain relief. Seven patients (mean age 31.3 years, range 24 to 49 years), five women and two men, were enrolled in the pilot study. Transcranial Doppler recordings were performed according to conventional procedure. Endothelin-1 concentrations were measured by means of radioimmunoassay, whereas nitric oxide levels were estimated using electron paramagnetic resonance spectroscopy. Ultrasound evaluation did not show significant changes during migraine attacks compared to the interictal condition. Nitric oxide levels showed only slight differences between basal and attack conditions (0.85 +/- 0.46 versus 1.56 +/- 0.88, expressed as arbitrary units), and were raised after pharmacological intervention (2.91 +/- 1.93, P < 0.05). Plasma endothelin-1 concentrations decreased during migraine attacks with respect to interictal conditions (3.99 +/- 1.21 pg/mL versus 4.23 +/- 1.19), and returned to basal values (4.44 +/- 1.08 pg/mL) after relief of pain. Coupling the measurements of systemic levels of nitric oxide and endothelin-1 with transcranial Doppler velocity results will provide useful information on the hemodynamic changes of cerebral blood flow regulation in migraineurs, thereby adding new insights into the mechanisms of the migraine attack.

Asymmetric dimethylarginine and nitric oxide levels in migraine during the interictal period

“…20 Nattero et al demonstrated higher serum NO levels during the migraine attack, but their patient group was very small (n = 7). 21 Similar to the findings of our study, several other studies reported insignificant NO À 2 and NO À 3 changes in plasma, 22 leukocytes and platelets 23 during the interictal period in patients with migraines as compared to the control group. However, none of these studies evaluated plasma ADMA levels in addition to NO metabolites.…”

Nitric oxide in primary headaches

“…The earliest findings of a slight increase in the peripheral levels of nitrites, consistent with a parallel increase in ET-1 levels, came from a study by Nattero et al [48] on migraine patients examined in interictical periods and during attacks. There is also evidence of an increase in nitrite levels in peripheral blood of migraine patients examined interictally [49].…”

Stress biomarkers' associations to pain in the neck, shoulder and back in healthy media workers: 12-month prospective follow-up

“…They suggest that their results motivate studies of endothelin as a potential novel therapy for neuropathic pain. Nattero et al 1996 [23] showed that plasma endothelin-1 concentrations decreased during migraine attacks. Endothelin was found to be associated with pain in the present study, as there were lower endothelin levels in the ''pain'' group as compared to ''no pain''.…”