Estrous cycle influences excitatory amino acid transport and visceral pain sensitivity in the rat: Effects of early-life stress

dc.contributor.authorMoloney, Rachel D.
dc.contributor.authorSajjad, Jahangir
dc.contributor.authorFoley, Tara
dc.contributor.authorFelice, Valeria D.
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.authorO'Mahony, Siobhain M.
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderHealth Research Board
dc.description.abstractBackground: Early-life stress (ELS) is a recognized risk factor for chronic pain disorders, and females appear to be more sensitive to the negative effects of stress. Moreover, estrous cycle-related fluctuations in estrogen levels have been linked with alternating pain sensitivity. Aberrant central circuitry involving both the anterior cingulate cortex (ACC) and the lumbosacral spinal cord has also been implicated in the modulation of visceral pain in clinical and preclinical studies. Here we further investigate changes in visceral pain sensitivity and central glutamatergic systems in rats with respect to estrous cycle and ELS. Methods: We investigated visceral sensitivity in adult female Sprague-Dawley rats, which had undergone maternal separation (MS) in early life or remained non-separated (NS), by performing colorectal distension (CRD). We also assessed excitatory amino acid uptake through excitatory amino acid transporters (EAATs) in the lumbosacral spinal cord and ACC. Results: NS animals in proestrus and estrus exhibited reduced EAAT uptake and decreased threshold to CRD. Moreover, total pain behaviors were increased in these stages. MS rats exhibited lower pain thresholds and higher total pain behaviors to CRD across all stages of the estrous cycle. Interestingly, cortical EAAT function in MS rats was inhibited in the low estrogen state—an effect completely opposite to that seen in NS rats. Conclusions: This data confirms that estrous cycle and ELS are significant factors in visceral sensitivity and fluctuations in EAAT function may be a perpetuating factor mediating central sensitization.en
dc.description.sponsorshipScience Foundation Ireland (Irish Government’s National Development Plan; 07/CE/B1368; 12/RC/2273); Health Research Board (Health Research Awards (HRA_POR/2011/23; HRA_POR/2012/32).en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationMoloney, R. D., Sajjad, J., Foley, T., Felice, V. D., Dinan, T. G., Cryan, J. F. and O’Mahony, S. M. (2016) 'Estrous cycle influences excitatory amino acid transport and visceral pain sensitivity in the rat: effects of early-life stress', Biology of Sex Differences, 7, 33 (8pp). doi:10.1186/s13293-016-0086-6en
dc.identifier.journaltitleBiology of Sex Differencesen
dc.publisherBioMed Centralen
dc.rights© 2016, the Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.en
dc.subjectVisceral painen
dc.subjectColorectal distensionen
dc.subjectEarly-life stressen
dc.subjectExcitatory amino acid transporteren
dc.subjectGlutamatergic systemen
dc.subjectAspartate uptakeen
dc.titleEstrous cycle influences excitatory amino acid transport and visceral pain sensitivity in the rat: Effects of early-life stressen
dc.typeArticle (peer-reviewed)en
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