Sarchielli P, Tognoloni M, Russo S, Vulcano M R, Feleppa M, Malà M, Sartori M, Gallai V
Interuniversity Center for the Study of Headache and Neurotransmitter Disorders, Universities of Perugia, Sassari, Bari, Italy.
Cephalalgia. 1996 Nov;16(7):468-75. doi: 10.1046/j.1468-2982.1996.1607468.x.
Previous studies have reported the existence of an arginine/nitric oxide (NO) pathway and the involvement of a Ca2+, NADPH-dependent nitric oxide synthase enzyme (NOS) in the generation of NO in human platelets. In the present research, we determined the rate of production of NO and cGMP in the cytosol of platelets stimulated by collagen in 20 females with menstrual migraine (MM), (age range 24-40 years), assessed in the follicular and luteal phases, interictally and ictally in the latter period. The same patients were also assessed at mid-cycle. At the same time, the variations in the collagen response of platelets were evaluated. Moreover, these parameters were determined in the same periods in 20 age-matched control females and in 20 females affected by non-menstrually related migraine (nMM). The collagen-stimulated production of NO in the cytosol of the platelet cytosol was significantly higher in migraine patients with MM than in the control subjects. In MM patients, the increase was greater in the luteal phase of the cycle than during the follicular phase (p < 0.005). A rise in NO production in platelets was also present, although to a lesser extent, in females affected by nMM compared to the healthy females, but this rise was most evident at ovulation (p < 0.001). A slight but significant increase was also observed at mid-cycle in control women, but this increase did not reach the values determined in the migraine groups (p < 0.02). NO production in platelets stimulated by collagen was significantly increased during attacks with respect to the interictal period in both patient groups. Similar variations were observed in the production of cGMP in MM and nMM patients. The increase in NO production was accompanied by a decrease in platelet aggregation in the migraine groups compared with the control group; this decrease was most evident at mid-cycle in nMM patients and in the luteal phase in MM patients. These data suggest an activation of the L-arginine/ NO pathway in MM and nMM patients which could explain the modifications in the platelet response to collagen evidenced in migraine-free periods and during attacks. The activation of this pathway is more accentuated in the luteal phase in MM patients, and this could be the cause of the increased susceptibility to migraine attacks in perimenstrual and menstrual periods in these patients.
先前的研究报告了精氨酸/一氧化氮（NO）途径的存在，以及一种Ca2+、NADPH依赖性一氧化氮合酶（NOS）参与人体血小板中NO的生成。在本研究中，我们测定了20名月经性偏头痛（MM）女性（年龄范围24 - 40岁）在卵泡期和黄体期、发作间期和发作期（后期），由胶原蛋白刺激的血小板胞质溶胶中NO和环磷酸鸟苷（cGMP）的生成速率。这些患者在月经周期中期也进行了评估。同时，评估了血小板对胶原蛋白反应的变化。此外，在20名年龄匹配的对照女性以及20名患有非月经相关性偏头痛（nMM）的女性的相同时间段内测定了这些参数。MM偏头痛患者血小板胞质溶胶中胶原蛋白刺激产生的NO显著高于对照组。在MM患者中，周期黄体期的增加幅度大于卵泡期（p < 0.005）。与健康女性相比，nMM女性血小板中NO生成也有增加，尽管程度较小，但这种增加在排卵时最为明显（p < 0.001）。对照女性在月经周期中期也观察到轻微但显著的增加，但这种增加未达到偏头痛组测定的值（p < 0.02）。在两个患者组中，发作期胶原蛋白刺激的血小板中NO生成相对于发作间期均显著增加。MM和nMM患者中cGMP生成也观察到类似变化。与对照组相比，偏头痛组中NO生成增加伴随着血小板聚集减少；这种减少在nMM患者月经周期中期和MM患者黄体期最为明显。这些数据表明MM和nMM患者中L - 精氨酸/NO途径被激活，这可以解释在无偏头痛期和发作期间血小板对胶原蛋白反应的改变。MM患者在黄体期该途径的激活更为明显，这可能是这些患者在围经期和月经期对偏头痛发作易感性增加的原因。
