Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients were studied both before, during an asymptomatic phase (t0), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide donor able to induce an experimental migraine attack (t1). The nitric oxide levels were analyzed as nitrite accumulation in serum samples, in peripheral blood mononuclear cell extracts, and culture supernatants. Basal nitrite levels in serum samples and peripheral blood mononuclear cell culture supernatants or migraine patients and healthy subjects indicated that migraine patients possess an activated nitric oxide synthesis pathway (t0 vs. CF = 8.16, P < 0.01 and F = 16.2, P < 0.01, respectively). As expected, in the migraine patients treated with the nitric oxide donor, a marked increase of nitrite levels was observed in sera (t1 vs. t0 P < 0.05, t = 3.05). In contrast, during the nitric oxide donor-induced migraine attacks a statistically significant decrease of nitrite levels in peripheral blood mononuclear cell culture supernatants was observed (t1 vs. t0 P < 0.01, t = -4.03), whereas a significant increase of nitrite in total cell extracts was detected (t1 vs. t0 P < 0.001, t = -6.89). These preliminary data suggest that nitric oxide could be involved in the neurovascular modifications leading to a migraine attack.