Gupta Saurabh, Villalón Carlos M, Mehrotra Suneet, de Vries René, Garrelds Ingrid M, Saxena Pramod R, MaassenVanDenbrink Antoinette
Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Headache. 2007 Feb;47(2):225-35. doi: 10.1111/j.1526-4610.2006.00526.x.
The prevalence of migraine is 2 to 3-fold higher in females than in males, and it is intricately related to the levels of female sex hormones. These hormones may regulate the synthesis and receptor expression of calcitonin gene-related peptide (CGRP), which mediates neurogenic dural vasodilatation and is implicated in migraine pathogenesis.
To investigate the effects of the female sex steroids, 17beta-estradiol and progesterone, separately and in combination, on dural vasodilatation induced by alphaCGRP, periarterial electrical stimulation and capsaicin in ovariectomized rats, using intravital microscopy.
Sprague-Dawley rats were ovariectomized and, 7 days later, subcutaneously implanted with 21-day release pellets of 17beta-estradiol, progesterone, their combination or placebo. On day 19 to 21, the animals were anesthetized, overlying bone thinned to visualize the middle meningeal artery and vasodilator responses to alphaCGRP (10 to 3000 ng kg(-1)), periarterial electrical stimulation (25 to 125 microA) and capsaicin (0.3 to 18 microg kg(-1)) elicited.
There were no significant differences in the vasodilator potency or efficacy of alphaCGRP or capsaicin in the different groups studied. In contrast, the vasodilator response to electrical stimulation was significantly higher in rats treated with 17beta-estradiol (Emax:157 +/- 19%) as compared to those observed after placebo treatment (Emax:93 +/- 11%).
Our results show that, in contrast to CGRP- or capsaicin-induced dural vasodilatation, 17beta-estradiol enhanced neurogenic vasodilatation, suggesting increased CGRP release from perivascular nerves. This may be one of the mechanisms through which 17beta-estradiol exacerbates migraine in women.
偏头痛在女性中的患病率比男性高2至3倍，并且与女性性激素水平密切相关。这些激素可能调节降钙素基因相关肽（CGRP）的合成和受体表达，CGRP介导神经源性硬脑膜血管舒张并与偏头痛发病机制有关。
使用活体显微镜研究雌性甾体激素17β-雌二醇和孕酮单独及联合使用对去卵巢大鼠中αCGRP、动脉周围电刺激和辣椒素诱导的硬脑膜血管舒张的影响。
将Sprague-Dawley大鼠去卵巢，7天后皮下植入17β-雌二醇、孕酮、它们的组合或安慰剂的21天缓释微丸。在第19至21天，将动物麻醉，使覆盖的骨变薄以观察脑膜中动脉，并引发对αCGRP（10至3000 ng kg(-1)）、动脉周围电刺激（25至125 μA）和辣椒素（0.3至18 μg kg(-1)）的血管舒张反应。
在所研究的不同组中，αCGRP或辣椒素的血管舒张效力或功效没有显著差异。相比之下，与安慰剂处理后观察到的大鼠（Emax：93 +/- 11%）相比，用17β-雌二醇处理的大鼠对电刺激的血管舒张反应显著更高（Emax：157 +/- 19%）。
我们的结果表明，与CGRP或辣椒素诱导的硬脑膜血管舒张相反，17β-雌二醇增强了神经源性血管舒张，表明血管周围神经释放的CGRP增加。这可能是17β-雌二醇加重女性偏头痛的机制之一。
