Triptan-induced disruption of trigemino-cortical connectivity
Triptan-induced disruption of trigemino-cortical connectivity
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DOI：
10.1212/wnl.0000000000001610
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发表时间：
2015-05-26
期刊：
影响因子：
9.9
通讯作者：
May, Arne
中科院分区：
文献类型：
--
作者：
Kroeger, Inga L.;May, Arne
目的：5-HT1B/D激动剂(Triptans)是一种特殊的头痛药物，本身对疼痛没有效果。尽管它们被常规用于偏头痛急性发作的治疗，但其潜在的作用机制仍存在争议。方法：43名健康受试者在标准化的fMRI范式中接受三叉神经伤害性刺激和控制刺激，同时进行fMRI检查。采用交叉、双盲、安慰剂对照设计，21名参与者(10名女性，平均年龄26.9岁，范围20-37岁)接受舒马曲坦治疗，22名参与者(11名女性，平均年龄25.5岁，22-32岁)接受乙酰水杨酸(ASA)治疗。在第一次fMRI数据采集期间，每组参与者被随机给予药物和生理盐水，其中一半接受生理盐水治疗，另一半接受各自的药物治疗。结果：虽然平均疼痛强度分级在对照组和药物之间没有显著差异，但我们发现舒马曲坦治疗后三叉神经核和丘脑的血氧水平依赖信号显著增加，与安慰剂或ASA相比。此外，我们还专门研究了三叉神经核和高级脑区(即三叉神经-皮质通路)之间的功能偶联的药理学调节，发现在生理盐水条件下存在强烈的偶联，舒马曲坦可以改变这种偶联，但服用ASA后不会改变这种偶联。结论：这些数据表明，三叉神经-皮质投射的特定功能抑制是曲普坦与止痛药不同的原因之一，它对头痛和偏头痛具有高度特异性，而对疼痛本身没有作用。
Objective:The 5-HT1B/D agonists (triptans) are specific headache medications that have no effect on pain as such. Although they are routinely used in the treatment of acute migraine attacks, the underlying mechanisms of action are still a matter of debate.Methods:Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a standardized fMRI paradigm. Using a crossover, double-blind, placebo-controlled design, 21 participants (10 women, mean age 26.9, range 20-37 years) received sumatriptan and 22 participants (11 women, mean age 25.5, range 22-32 years) received acetylsalicylic acid (ASA). Administration of medication and saline was randomized between participants of each group resulting in half of the participants receiving saline and the other half receiving the respective medication during the first fMRI data acquisition.Results:While mean pain intensity ratings did not differ significantly between control and medication nor between medications, we found a significant blood oxygen level-dependent signal increase in the trigeminal nuclei and the thalamus after sumatriptan treatment compared with placebo or ASA. In addition, we specifically looked for the pharmacologic modulation of functional coupling between trigeminal nuclei and higher brain areas, i.e., trigemino-cortical pathways, and found a strong coupling during the saline condition, which was altered by sumatriptan but not after ASA administration.Conclusion:These data suggest that a specific functional inhibition of trigemino-cortical projections is one of the reasons that triptans, unlike pain killers, act highly specifically on headache and migraine but not pain as such.