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, 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.


METHODS
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.


RESULTS
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%).


CONCLUSIONS
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.
Gupta
Saurabh
S
Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Villalón
Carlos M
CM
Mehrotra
Suneet
S
de Vries
René
R
Garrelds
Ingrid M
IM
Saxena
Pramod R
PR
MaassenVanDenbrink
Antoinette
A
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D004388:Dura Mater / Q000098:blood supply*; D004558:Electric Stimulation; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008576:Meningeal Arteries / Q000502:physiology; D008881:Migraine Disorders / Q000503:physiopathology*; D010052:Ovariectomy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D014665:Vasodilator Agents; D011374:Progesterone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin