Female sex hormones and rat dural vasodilatation to CGRP, periarterial electrical stimulation and capsaicin
Background. - 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. Objective. - To investigate the effects of the female sex steroids, 17β-estradiol and progesterone, separately and in combination, on dural vasodilatation induced by αCGRP, periarterial electrical stimulation and capsaicin in ovariectomized rats, using intravital microscopy. Methods. - Sprague-Dawley rats were ovariectomized and, 7 days later, subcutaneously implanted with 21-day release pellets of 17β-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 αCGRP (10 to 3000 ng kg-1), periarterial electrical stimulation (25 to 125 μA) and capsaicin (0.3 to 18 μg kg-1) elicited. Results. - There were no significant differences in the vasodilator potency or efficacy of αCGRP or capsaicin in the different groups studied. In contrast, the vasodilator response to electrical stimulation was significantly higher in rats treated with 17β-estradiol (Emax:157 ± 19%) as compared to those observed after placebo treatment (Emax:93 ± 11%). Conclusion. - Our results show that, in contrast to CGRP- or capsaicin-induced dural vasodilatation, 17β-estradiol enhanced neurogenic vasodilatation, suggesting increased CGRP release from perivascular nerves. This may be one of the mechanisms through which 17β-estradiol exacerbates migraine in women.