Mitsikostas D D, Sanchez del Rio M
Athens Naval Hospital, Neurology Department, Headache Clinic, 70 Dinokratous Street, 115 21, Athens, Greece.
Brain Res Brain Res Rev. 2001 Mar;35(1):20-35. doi: 10.1016/s0165-0173(00)00048-5.
In intracranial structures unmyelinated C- and Adelta-fibers of the trigeminal nerve transmit pain stimuli from meninges to the trigeminal nucleus caudalis (Sp5C). Peripheral nerve endings surround meningeal vessels (the so-called trigeminovascular system) and contain vasoactive neuropeptides (calcitonin gene-related peptide, substance P and neurokinin A). Activation of the trigeminovascular system promotes a meningeal sterile inflammatory response through the release of neuropeptides by peripheral endings. Orthodromic conduction along trigeminovascular fibers transmits information centrally with induction of immediate early c-fos gene within post-synaptic Sp5C neurons, as a marker of neuronal activity within central nociceptive pathways. In laboratory animals the system is activated by either electrical stimulation of the TG, chemical stimulation of the meninges, electrical or mechanical stimulation of the superior sagittal sinus or by induction of cortical spreading depression. All these techniques induce c-fos within Sp5C and are used as a rodent/feline model of vascular headache in humans. Up-to-date there is evidence that at least ten receptors (5-HT(1B), 5-HT(1D), 5-HT(lF), 5-HT(2B), NK-1, GABA(A), NMDA, AMPA, class III metabotropic glutamate receptors, and opioids mu receptors) modulate c-fos expression within Sp5C. These receptors represent potential targets for anti-migraine drugs as shown by triptans (5-HT(1B/1D/1F)) and ergot alkaloids (5-HT(1A1B/1D/1F)). This review discusses the importance of c-fos expression within Sp5C as a marker of cephalic nociception, the different cephalic pain models that induce c-fos within Sp5C, the receptors involved and their potential role as targets for anti-migraine drugs.
在颅内结构中，三叉神经无髓鞘的C纤维和Aδ纤维将来自脑膜的疼痛刺激传递至三叉神经尾侧核（Sp5C）。外周神经末梢围绕脑膜血管（即所谓的三叉神经血管系统），并含有血管活性神经肽（降钙素基因相关肽、P物质和神经激肽A）。三叉神经血管系统的激活通过外周末梢释放神经肽促进脑膜无菌性炎症反应。沿三叉神经血管纤维的顺向传导将信息向中枢传递，诱导突触后Sp5C神经元内即刻早期c-fos基因表达，作为中枢伤害性感受通路内神经元活动的标志物。在实验动物中，该系统可通过以下方式激活：三叉神经节的电刺激、脑膜的化学刺激、上矢状窦的电刺激或机械刺激，或通过诱导皮层扩散性抑制。所有这些技术均可诱导Sp5C内的c-fos表达，并被用作人类血管性头痛的啮齿动物/猫模型。目前有证据表明，至少十种受体（5-HT(1B)、5-HT(1D)、5-HT(1F)、5-HT(2B)、NK-1、GABA(A)、NMDA、AMPA、III类代谢型谷氨酸受体和阿片类μ受体）可调节Sp5C内的c-fos表达。如曲坦类药物（5-HT(1B/1D/1F)）和麦角生物碱（5-HT(1A1B/1D/1F)）所示，这些受体是抗偏头痛药物的潜在靶点。本综述讨论了Sp5C内c-fos表达作为头部伤害感受标志物的重要性、诱导Sp5C内c-fos表达的不同头部疼痛模型、涉及的受体及其作为抗偏头痛药物靶点的潜在作用。
