Nicolodi M, Sicuteri F, Sicuteri R
Centro Interuniversitario di Neurochimica e Farmacologia, Università degli Studi di Firenze.
Ann Ital Med Int. 1992 Jul-Sep;7(3 Suppl):7S-22S.
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.
在经历了数千次痛苦且持久的偏头痛或极其剧烈的丛集性头痛发作后，尚未有人发现相关组织的组织学炎症或退行性改变能够解释如此剧烈的疼痛。因此，将这些疼痛归为无正当理由、无目的、未终结类型的疼痛似乎是合乎逻辑的。此外，这些疼痛的自主性、爆发性及病程的临床特征与其他无目的疼痛相似，比如有机性传入神经阻滞（幻肢痛）的疼痛，这种疼痛出现在去神经支配后的感觉减退肢体甚至截肢者身上。阿片类药物戒断时的强烈且持久的疼痛，主要位于胸部和髋部，也具备无目的疼痛的所有特征。特发性头痛，连同传入神经阻滞性疼痛或阿片类药物戒断性疼痛，似乎是由于传入神经功能障碍所致，通过不同途径，遵循类似的机制。这种机制似乎是由于自身镇痛功能不足，在有机性传入神经阻滞（幻肢）和阿片类药物戒断中，这可能与传入神经调制的废用有关。在特发性头痛中，这种自身镇痛功能的失效可能归因于遗传、特发性机制。头痛的特征是明显缺乏自身镇痛功能，这不仅可能在富含传入神经的头部节段层面表现出来，甚至可能累及全身。即便疼痛是诊断头痛的必要现象，但必须考虑到偏头痛是一种有症状的三联征，其中自主神经和情绪现象也会出现。这些现象相互独立而非相互依存，因为它们中的每一个都可能作为发作的首发表现出现；因此必须考虑存在“单一驱动因素”的可能性。血清素因其作用涉及所有或几乎所有自主神经 - 情绪疼痛传递途径而被考虑在内。如今对5 - HT受体的四种类型及各种亚型的鉴定揭示了这种递质的非凡折衷性，在偏头痛的临床表型中突出表明偏头痛患者对所有能够急性或慢性影响血清素代谢并与多种血清素受体类型及亚型结合的药物具有显著敏感性。所以，即便偏头痛之谜依旧未解，满怀无尽好奇心的研究人员不仅可能为众多人类找到越来越精确有效的药物，还可能开始洞察一个谜团，这对人类想象力而言是巨大的挑战。
