[Noci-autonomic-affective automatism, the physiopathological essence of hemicrania. The serotonin theory as a guiding principle in the labyrinth of interpretations].

After thousands of painful long-lasting migraine or extremely violent cluster headache attacks no one has yet traced histological inflammatory or degenerative alterations of the interested tissues able to explain such dreadful pain. Therefore it has seemed logical to include these pains among the unjustified aimless, non finalized types of pain. Furthermore, clinical characteristics of automatism, explosiveness and the course of these pains resemble other aimless pains like those of organic deafferentation (phantom pain) which appear in a desensitized limb after denervation or even in amputated subjects. Intense and long lasting pains in opioid abstinence, mainly located in the chest and in the hip, also have all the characteristics of aimless pain. Idiopathic cephalic pain, together with deafferentation or opioid-abstinence pain, seems to be due to a dysafferentation which, through different channels, follows an analogous mechanism. This mechanism seems to be due to a deficit of autoanalgesia which in both organic deafferentation (phantom limb) and in opioid-abstinence can be related to the disuse of afferences' modulation. In idiopathic headache such a failure of autoanalgesia is likely to be due to a genetic, idiopathic mechanism. Headaches are characterized by a clear deficiency of autoanalgesia which may manifest itself not only at the level of the cephalic segment, which is so rich in afferences, but it may even involve the whole body. Even if pain is the compulsory phenomenon to diagnose headache, one must consider that migraine is a symptomatic triad in which vegetative and emotional phenomena also emerge. These phenomena are interindependent and not interdependent as each of them may appear as a first manifestation of an attack; one must therefore consider the possibility of a "unicum movens". Serotonin was taken into consideration because of its action which interests all or nearly all vegetative-emotional pain transmitting pathways. Today's identification of four types and various sub-types of 5-HT receptors has revealed the extraordinary eclecticism of this transmitter which within migraine's clinical expression underscores that migraine sufferers are characterized by a marked sensitivity to all the drugs capable of acutely or chronically interacting with serotonin metabolism and binding with many serotonin receptor types and sub-types. So even if the migraine sphinx still proposes its enigma, researchers--with their incurable curiosity--may not only find more and more accurate and effective medication for many human beings but also start penetrating a mystery, a great challenge to human imagination.