17-β-Estradiol induces spreading depression and pain behavior in alert female rats
AuthorSandweiss, Alexander J.
Cottier, Karissa E.
McIntosh, Mary I.
Davis, Thomas P.
Vanderah, Todd W.
Largent-Milnes, Tally M.
AffiliationUniv Arizona, Coll Med, Dept Pharmacol
MetadataShow full item record
PublisherIMPACT JOURNALS LLC
Citation17-β-Estradiol induces spreading depression and pain behavior in alert female rats 2017, 8 (69) Oncotarget
Rights© Sandweiss et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractAims: Test the putative contribution of 17-beta-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods: Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-beta-estradiol (180 mu g/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed. Key Findings: A bolus of 17-beta-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-beta-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used. Significance: These data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact-rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies.
VersionFinal published version
SponsorsUniversity of Arizona Medical Pharmacology Departmental funding; NIH [5 RO1 DA 11271-18, 5 RO1 NS 42652-14]
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