偏头痛的科学。
The science of migraine.
机构信息
Departments of Anesthesia, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
出版信息
J Vestib Res. 2011;21(6):305-14. doi: 10.3233/VES-2012-0433.
The cardinal symptom of migraine is headache pain. In this paper we review the neurobiology of this pain as it is currently understood. In recent years, we discovered that the network of neurons that sense pain signals from the dura changes rapidly during the course of a single migraine attack and that the treatment of an attack is a moving target. We found that if the pain is not stopped within 10-20 minutes after it starts, the first set of neurons in the network, those located in the trigeminal ganglion, undergo molecular changes that make them hypersensitive to the changing pressure inside the head, which explains why migraine headache throbs and is worsened by bending over and sneezing. We found that if the pain is not stopped within 60-120 minutes, the second group of neurons in the network, those located in the spinal trigeminal nucleus, undergoes molecular changes that convert them from being dependent on sensory signals they receive from the dura by the first set of neurons, into an independent state in which they themselves become the pain generator of the headache. When this happens, patients notice that brushing their hair, taking a shower, touching their periorbital skin, shaving, wearing earrings, etc become painful, a condition called cutaneous allodynia. Based on this scenario, we showed recently that the success rate of rendering migraine patients pain-free increased dramatically if medication was given before the establishment of cutaneous allodynia and central sensitization. The molecular shift from activity-dependent to activity-independent central sensitization together with our recent conclusion that triptans have the ability to disrupt communications between peripheral and central trigeminovascular neurons (rather than inhibiting directly peripheral or central neurons) explain their clinical effects. Both our clinical and pre-clinical findings of the last five years point to possible short- and long-term advantages in using an early-treatment approach in the treatment of acute migraine attacks.
偏头痛的主要症状是头痛。本文综述了目前对这种疼痛的神经生物学认识。近年来，我们发现，在单一偏头痛发作过程中，感知硬膜疼痛信号的神经元网络会迅速变化，而治疗发作是一个动态目标。我们发现，如果疼痛在开始后 10-20 分钟内未得到缓解，网络中的第一组神经元（位于三叉神经节中的神经元）会发生分子变化，使其对头部内部变化的压力变得异常敏感，这解释了为什么偏头痛头痛会悸动，并因弯腰和打喷嚏而加重。我们发现，如果疼痛在 60-120 分钟内未得到缓解，网络中的第二组神经元（位于脊髓三叉神经核中的神经元）会发生分子变化，使其从依赖第一组神经元从硬膜接收的感觉信号转变为独立状态，从而成为头痛的疼痛发生器。当这种情况发生时，患者会注意到梳理头发、洗澡、触摸眼眶皮肤、刮胡子、戴耳环等变得疼痛，这种情况称为皮肤感觉过敏。基于这种情况，我们最近表明，如果在皮肤感觉过敏和中枢敏化建立之前给予药物，使偏头痛患者无痛的成功率会大大提高。从活动依赖性到活动独立性的中枢敏化的分子转变，以及我们最近的结论，即曲坦类药物具有破坏外周和中枢三叉血管神经元之间通讯的能力（而不是直接抑制外周或中枢神经元），解释了它们的临床效果。我们过去五年的临床和临床前发现表明，在急性偏头痛发作的治疗中采用早期治疗方法可能具有短期和长期优势。
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