Serotonergic hypofunction in migraine: a synthesis of evidence based on platelet dense body dysfunction

We studied the platelet dense body as a model for serotonergic vesicular function. Headache-free migraine sufferers had increased numbers of dense bodies, decreased dense body secretion, a defective link between cytosolic ionized calcium and platelet activation, an abnormal sensitivity to activation by platelet-activating factor and decreased serotonin metabolism in the presence of an unactivated platelet. These findings are interpreted as evidence for low platelet serotonin turnover. Also an abnormality in coupling of secretion to cytosolic ionized calcium caused by a membranal defect results in reduced platelet secretory function. A similar abnormality is postulated for serotonergic vesicles in central neurons. Central serotonergic hypofunction in migraine sufferers may reduce this normally present inhibitory influence on the intrinsic noradrenergic system, the activation of which may initiate the neuronal mechanisms of migraine.