Ghelardini Carla, Galeotti Nicoletta, Grazioli Irene, Uslenghi Carla
Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.
J Pain. 2004 Oct;5(8):413-9. doi: 10.1016/j.jpain.2004.06.008.
Recently it has been proposed that the throbbing pain of migraine is mediated by sensitization of peripheral trigeminovascular neurons, and that cutaneous allodynia of migraine is mediated by sensitization of central trigeminovascular neurons, and, moreover, that the triptans are less effective in aborting a migraine attack if the central sensitization is already established. The combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) is a drug of well-established use in the acute treatment of migraine. The aim of this study was to investigate whether the 3 active principles of IndoProCaf, alone and combined, compared to sumatriptan, were able to abolish the peripheral sensitization induced by kainic acid and the central sensitization induced by N-methyl-D-aspartate (NMDA) in in vivo models of hyperalgesia. The study showed that indomethacin or IndoProCaf is able to abolish both the kainic acid-induced and the NMDA-induced hyperalgesia. If administered at different times, IndoProCaf was always effective in reversing the kainic acid-induced hyperalgesia. Sumatriptan was not able to reverse either the kainic acid-induced or the NMDA-induced hyperalgesia. The efficacy of indomethacin, alone and combined with prochlorperazine and caffeine, in abolishing peripheral and central sensitization in in vivo models of hyperalgesia is a further explanation of the clinical efficacy of IndoProCaf in the treatment of migraine.
This study suggests that, although triptans were shown to be able to abort migraine attacks only if given before the establishment of cutaneous allodynia and central sensitization, IndoProCaf should be able to abort migraine attacks independently from the time of administration, because it is able to abolish an already established peripheral and central sensitization.
最近有人提出，偏头痛的搏动性疼痛是由外周三叉神经血管神经元的敏化介导的，偏头痛的皮肤异常性疼痛是由中枢三叉神经血管神经元的敏化介导的，而且，如果中枢敏化已经确立，曲坦类药物在中止偏头痛发作方面的效果会较差。吲哚美辛、丙氯拉嗪和咖啡因的组合（IndoProCaf）是一种在偏头痛急性治疗中已确立用途的药物。本研究的目的是调查IndoProCaf的三种活性成分单独使用和联合使用时，与舒马曲坦相比，是否能够在痛觉过敏的体内模型中消除由 kainic 酸诱导的外周敏化和由 N-甲基-D-天冬氨酸（NMDA）诱导的中枢敏化。研究表明，吲哚美辛或 IndoProCaf 能够消除 kainic 酸诱导的和 NMDA 诱导的痛觉过敏。如果在不同时间给药，IndoProCaf 总能有效逆转 kainic 酸诱导的痛觉过敏。舒马曲坦无法逆转 kainic 酸诱导的或 NMDA 诱导的痛觉过敏。吲哚美辛单独使用以及与丙氯拉嗪和咖啡因联合使用时，在痛觉过敏的体内模型中消除外周和中枢敏化的功效，进一步解释了 IndoProCaf 在偏头痛治疗中的临床疗效。
本研究表明，尽管曲坦类药物只有在皮肤异常性疼痛和中枢敏化确立之前给药才能中止偏头痛发作，但 IndoProCaf 应该能够独立于给药时间中止偏头痛发作，因为它能够消除已经确立的外周和中枢敏化。
