Landy Stephen, Rice Kathryn, Lobo Bob
Wesley Headache Clinic and University of Tennessee Medical School, Memphis, Tennessee, USA.
CNS Drugs. 2004;18(6):337-42. doi: 10.2165/00023210-200418060-00001.
Cutaneous allodynia, pain resulting from application of a non-noxious stimulus to normal skin, is a recently described symptom of migraine, with a potential role in directing optimal treatment for migraine attacks. Manifestations of cutaneous allodynia include discomfort when combing the hair, shaving, and wearing glasses, contact lenses, earrings or tight clothing. The exact mechanism by which a migraine attack is triggered is not known, but it has been theorised that, in some patients, once the attack has begun, central neurons can propagate information about the pain process without the need for further external stimuli. This process is termed central sensitisation. The trigeminal nerves, which innervate intracranial and extracranial tissues, account for head pain and other symptoms in migraine. The first-order neurons in the trigeminal ganglion receive input from the dural blood vessels, which is transmitted to second-order neurons in the trigeminal brain stem nuclear complex and is finally sent to the third-order neurons in the thalamus. Studies in humans and animals have shown that migraine pain progresses along this neural pathway, with throbbing head pain occurring early in the attack (sensitisation of first-order neurons), followed by central sensitisation and cutaneous allodynia within the referred pain area (second-order) and finally extracephalic allodynia (third-order). The data also indicate that once central sensitisation is established in the second- and third-order neurons, migraine treatment designed to prevent the initiation of central sensitisation can lessen the pain to some extent but cannot reverse it. Thus, treatment affecting the initiation of central sensitisation should be administered immediately after the onset of migraine pain to prevent intracranial hypersensitivity and the establishment of allodynia. The serotonin 5-HT(1B/1D) agonist anti-migraine agents (the 'triptans') block meningeal nociceptor transmission at presynaptic sites in the dorsal horn. Studies have shown that triptan therapy can abort pain prior to the development of central sensitisation, but not after allodynia has been established. Therefore, in the subset of patients who report symptoms of cutaneous allodynia with migraine attacks, early initiation of triptan therapy is currently the best intervention to achieve rapid, complete and sustained pain relief.
皮肤异常性疼痛是指对正常皮肤施加非伤害性刺激所产生的疼痛，这是最近描述的偏头痛症状，在指导偏头痛发作的最佳治疗方面可能发挥作用。皮肤异常性疼痛的表现包括梳头、剃须以及佩戴眼镜、隐形眼镜、耳环或紧身衣物时的不适感。偏头痛发作的确切触发机制尚不清楚，但据推测，在一些患者中，一旦发作开始，中枢神经元可以在无需进一步外部刺激的情况下传递有关疼痛过程的信息。这个过程被称为中枢敏化。支配颅内和颅外组织的三叉神经是偏头痛头痛和其他症状的原因。三叉神经节中的一级神经元接收来自硬脑膜血管的输入，该输入被传递到三叉神经脑干核复合体中的二级神经元，并最终发送到丘脑的三级神经元。对人类和动物的研究表明，偏头痛疼痛沿着这条神经通路发展，搏动性头痛在发作早期出现（一级神经元敏化），随后在牵涉痛区域内出现中枢敏化和皮肤异常性疼痛（二级），最后是颅外异常性疼痛（三级）。数据还表明，一旦在二级和三级神经元中建立了中枢敏化，旨在防止中枢敏化启动的偏头痛治疗可以在一定程度上减轻疼痛，但无法逆转它。因此，应在偏头痛疼痛发作后立即给予影响中枢敏化启动的治疗，以防止颅内超敏反应和异常性疼痛的建立。5-羟色胺5-HT(1B/1D)激动剂抗偏头痛药物（“曲坦类药物”）在背角的突触前部位阻断脑膜伤害感受器的传递。研究表明，曲坦类药物治疗可以在中枢敏化发展之前中止疼痛，但在异常性疼痛建立之后则不行。因此，在报告有偏头痛发作伴皮肤异常性疼痛症状的患者亚组中，早期开始曲坦类药物治疗目前是实现快速、完全和持续缓解疼痛的最佳干预措施。
