Neurogenic inflammation including calcitonin gene-related peptide (CGRP) and substance-P (SP) release plays a pivotal role in migraine pathogenesis. Prevalence of migraine is ~ 3 folds higher in women than in men, but its underlying mechanisms remained unclear. We investigated the effects of female sex hormones estrogen and progesterone on CGRP and SP in in-vivo and ex-vivo in rats of both sexes. For in-vivo experiments, male, female and ovariectomized rats were separated into four groups (n = 7) as control, estrogen, progesterone and estrogen + progesterone, respectively. Groups received daily intraperitoneal vehicle, 17β-estradiol, progesterone and 17β-estradiol + progesterone for 5 days, respectively. For ex-vivo experiments in both sexes, isolated trigeminal ganglia and hemiskull preparations were divided into four groups (n = 6 or 8), respectively, as in-vivo groups, and administered the same test substances. CGRP and SP contents in plasma and superfusates were determined using ELISA. In in-vivo experiments, 17β-estradiol decreased CGRP levels in males and SP levels in ovariectomized rats. Progesterone increased both CGRP and SP levels in females. Their combination decreased both CGRP and SP levels in males, and only SP levels in ovariectomized rats. In ex-vivo experiments, 17β-estradiol reduced CGRP release in males and SP release in females in trigeminal ganglia. While progesterone increased CGRP release in trigeminal ganglia, it reduced SP release from hemiskulls in both sexes. Their combination restored progesterone-mediated changes in neuropeptides releases in both trigeminal ganglia and hemiskulls in both sexes. Estrogen alleviates neurogenic inflammation through modulation of CGRP and SP release. Progesterone has dual effects on these neuropeptides in different sites associated with migraine pain.

包括降钙素基因相关肽（CGRP）和P物质（SP）释放在内的神经源性炎症在偏头痛发病机理中起关键作用。女性偏头痛的患病率比男性高约3倍，但其潜在机制仍不清楚。我们调查了雌性激素雌激素和孕酮对雌雄同体大鼠体内和体外CGRP和SP的影响。对于体内实验，将雄性，雌性和去卵巢大鼠分为四组（n = 7）作为对照，分别使用雌激素，孕酮和雌激素+孕酮。各组分别接受每日腹膜内溶媒，17β-雌二醇，孕酮和17β-雌二醇+孕酮5天。对于男女的离体实验，将孤立的三叉神经节和hemiskull制剂分为四组（n = 6或8）分别作为体内组，并施用了相同的测试物质。使用ELISA测定血浆和超融合液中的CGRP和SP含量。在体内实验中，17β-雌二醇可降低雄性大鼠的CGRP水平和去卵巢大鼠的SP水平。孕激素增加女性的CGRP和SP水平。他们的组合降低了雄性的CGRP和SP水平，而在去卵巢大鼠中仅降低了SP水平。在离体实验中，三叉神经节中17β-雌二醇降低了雄性的CGRP释放和降低了雌性的SP释放。孕酮虽然增加了三叉神经节中CGRP的释放，但降低了男女两性成员从hemiskulls中释放的SP。他们的组合恢复了黄体酮介导的男女三叉神经节和hemiskulls中神经肽释放的变化。雌激素通过调节CGRP和SP释放减轻神经性炎症。孕酮在与偏头痛相关的不同部位对这些神经肽具有双重作用。