Christiansen I, Iversen H K, Olesen J
Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark.
Cephalalgia. 2000 Jun;20(5):445-54. doi: 10.1046/j.1468-2982.2000.00068.x.
The aims of the present study were to investigate whether induction of nitrate tolerance is a useful treatment in cluster headache and to correlate any changes in attack frequency of cluster headache and nitrate-induced headache to the vascular adaptation during continuous nitrate administration. The results were compared to results obtained from studies of nitrate tolerance in healthy subjects.
5-isosorbide-mononitrate (5-ISMN) 30 mg was administered orally three times daily for 4 weeks in nine sufferers of chronic cluster headache in a double-blind, randomized placebo-controlled cross-over design. Blood velocity in the middle cerebral artery was measured with transcranial Doppler and the diameters of the temporal and radial arteries were measured with high frequency ultrasound. The haemodynamic data were compared to changes in the frequency of cluster headache attacks and interval headaches over time.
Tolerance was complete within 24 h in the middle cerebral arteries and after 7 days in the symptomatic temporal artery, while tolerance of the radial artery was not observed within this period. The time profiles of tolerance were almost identical to the time profiles observed in healthy subjects. A close temporal association between the disappearance of nitrate-induced headache and tolerance of the temporal artery was observed but tolerance had no effect on cluster headache attack frequency.
Induction of tolerance to nitrates cannot be used to treat cluster headache. If pain is related to arterial dilatation the results point to extracerebral rather than cerebral arteries as the site of nociception. However, other peripheral and central pain-modulating effects of nitric oxide, the time courses of which are unknown, should also be taken into consideration.
本研究的目的是调查诱导硝酸盐耐受性是否是治疗丛集性头痛的有效方法，并将丛集性头痛发作频率和硝酸盐诱发头痛的任何变化与持续给予硝酸盐期间的血管适应性相关联。将结果与健康受试者硝酸盐耐受性研究的结果进行比较。
在一项双盲、随机、安慰剂对照的交叉设计中，9名慢性丛集性头痛患者每日口服3次30 mg单硝酸异山梨酯（5-ISMN），持续4周。用经颅多普勒测量大脑中动脉的血流速度，用高频超声测量颞动脉和桡动脉的直径。将血流动力学数据与丛集性头痛发作频率和间歇性头痛随时间的变化进行比较。
大脑中动脉在24小时内完全产生耐受性，症状性颞动脉在7天后产生耐受性，而在此期间桡动脉未观察到耐受性。耐受性的时间曲线与在健康受试者中观察到的时间曲线几乎相同。观察到硝酸盐诱发头痛的消失与颞动脉耐受性之间存在密切的时间关联，但耐受性对丛集性头痛发作频率没有影响。
诱导对硝酸盐的耐受性不能用于治疗丛集性头痛。如果疼痛与动脉扩张有关，结果表明伤害感受的部位是脑外动脉而非脑动脉。然而，一氧化氮的其他外周和中枢疼痛调节作用，其时间进程尚不清楚，也应予以考虑。
