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Many platelet abnormalities have been described in migraine, but they are now regarded as secondary phenomena rather than primary causative factors. In this study, we attempted to assess the presence of bioamine-releasing factors in the plasma of patients with common, non-dietary migraine. Blood samples were collected from 17 such patients, either during attacks (n = 9) or during attack-free periods (n = 8). Ten healthy volunteers served as controls. Release experiments were performed by adding 1 volume as controls. Release experiments were performed by adding 1 volume of migraineur's platelet-poor plasma to 1 volume of either control's whole blood (histamine release) or isolated platelets (catecholamines or serotonin release). Endogenous unconjugated bioamines were measured in whole blood and in isolated platelets from migraineurs' blood collected during and between attacks. We also measured plasma levels of histamine and of unconjugated and conjugated serotonin and catecholamines, as well as the inhibition of serotonin uptake and labelled serotonin release from controls' platelets in the presence of migraineurs' plasma collected during or between attacks. The results obtained suggest the presence of two plasma bioamine-releasing factors: a histamine-releasing factor present in migraineurs' blood during and between attacks, and a catecholamine and serotonin releasing factor present only during attacks in migraineurs' platelet-poor plasma. The latter factor is thermolabile and dialysable, with an apparent molecular weight lower than 16 kd. Gel-filtered fractions of semi-purified catecholamine-serotonin releasing factor induced the same events as the migraineurs' platelet-poor plasma from which they were obtained.

Platelet serotonin uptake characteristics (Km, Vmax, y) were determined in platelet-rich plasma for 11 common migraineurs and 15 health volunteers. All three parameters were decreased only for the three patients having a migraine attack during blood collection, Migrainous platelets isolated on dextran or resuspended in control plasma exhibited normal serotonin uptake. This finding suggests that plasmatic factor(s) may be responsible for the decrease of platelet serotonin uptake observed during migraine attacks.

Plasma levels of conjugated and unconjugated catecholamines were measured in 27 migraineurs between attacks, in 9 migraineurs 1 to 2 hours after the onset of an attack, and in 30 controls. There were no significant changes in conjugated catecholamines; in contrast, a significant rise (p less than 0.01; KS test) in unconjugated dopamine, noradrenaline and adrenaline levels was observed during attacks. These results confirm that migrainous attacks are associated with platelet activation and with overactivity of the sympathetic system.

Some studies suggested a role for histamine in the pathogenesis of the migraine. So we decided to investigate the histamine-release in two groups of patients: 8 common migraine patients, 8 healthy subjects. Plasma from either controls or migraineurs were mixed with the same control whole blood and histamine release was measured using a radio-enzymatic assay. Migraine plasma induced an histamine release significantly more important than control plasma (p less than 0.01). The nature of an "histamine releasing factor" in the plasma of migraine patient is discussed. This work is an argument for a possible immuno-allergic process in migraine.

Concentrations and uptake of platelet conjugated and unconjugated serotonin were measured in 15 healthy subjects and in 19 patients with common migraine. Venous blood was taken between migrainous attacks in all patients and during attacks in 8 of them. A significant decrease in unconjugated serotonin concentrations was observed during the attacks, whereas conjugated serotonin concentrations were the same as in controls. In addition, migrainous attacks were accompanied by a significant decrease in serotonin uptake by the platelets, with fall in Km, Vmax and -y. This abnormality was corrected when platelets removed from patients during attacks were incubated in plasma from controls, but it persisted when platelets from controls were incubated in plasma taken from patients during attacks. These findings suggest that one or several factors present in plasma are responsible for the decrease in serotonin uptake observed during migrainous attacks. Finally a study of correlations between these changes and the time elapsed since the last migrainous attacks demonstrated cyclic variations in abnormalities between attacks.

Whole blood and plasma histamine levels were measured in 27 non-medicated patients with common migraine. In nine cases blood was drawn 1-2 h after the onset of a migraine attack. The whole blood histamine levels of migraineurs and controls did not differ significantly. In contrast, histamine levels were significantly increased in plasma from patients both during and between migraine attacks, as compared with controls (p less than 0.001). Finally, plasma taken from migraine patients induced a significantly greater release of histamine from control whole blood than did plasma taken from control subjects (p less than 0.01).

Several arguments suggest that dopamine (DA) plays a role in the physiopathology of migraine. Conjugated and unconjugated plasma and platelet DA, as well as platelet phenolsulfotransferase M activity (responsible for DA sulfatation) were measured in 30 control subjects, 27 common migraine patients between attacks and 9 migraineurs during an attack. No modification of any of the parameters tested was detected in attack-free periods. During the attack no change of conjugated DA was observed; in contrast, a significant decrease of unconjugated platelet DA and a significant and correlated increase of plasma unconjugated DA were demonstrated. This corresponds to a release of unconjugated DA by the very dense bodies in platelets of migraine patients during the attack.