Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurology, KMG Medical Center, Güstrow, Germany.
Eur J Pain. 2022 Nov;26(10):2152-2161. doi: 10.1002/ejp.2027. Epub 2022 Sep 14.
The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain.
Forty healthy participants were enrolled in this double-blinded, randomized, placebo-controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin-induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing.
After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome.
Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin-induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain.
Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome-specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks.
曲坦类药物在偏头痛发作中的确切作用机制和作用部位仍存在争议。我们假设曲坦类药物的临床疗效在于终止中枢敏化，并专注于为什么曲坦类药物是头痛特异性的问题，即在偏头痛和丛集性头痛中非常有效，而在非头痛性疼痛中无效。
本研究纳入了 40 名健康志愿者，采用双盲、随机、安慰剂对照的方法，研究舒马曲坦（n=20）与安慰剂（n=20）对三叉神经（V1）与非头部皮肤（前臂）的影响，采用辣椒素敏化模型。使用定量感觉测试评估辣椒素诱导的原发性和继发性痛觉过敏。
在辣椒素应用后，舒马曲坦组和安慰剂组在两个皮区均出现原发性痛觉过敏。然而，舒马曲坦仅在 V1 皮区阻止了继发性痛觉过敏，但在前臂无效。安慰剂对三叉神经和非头部皮肤的继发性痛觉过敏均无影响。此外，舒马曲坦仅减少了 V1 皮区的红斑面积。
我们的数据表明，舒马曲坦在辣椒素诱导的敏化人类疼痛模型中可减少中枢敏化（继发性痛觉过敏），而不调节外周敏化（原发性痛觉过敏）。此外，尽管舒马曲坦全身给药，但其调节作用是三叉神经特异性的，与曲坦类药物终止头痛发作的临床疗效相呼应，但对非头痛性疼痛无效。
我们的数据表明，曲坦类药物通过抑制中枢敏化发挥疗效。通过揭示皮区特异性调节，本研究显示了曲坦类药物的药效学与三叉神经伤害感受系统之间以前未被认识的相互作用，为曲坦类药物如何在终止头痛发作中发挥作用提供了新的见解。
