Stress-induced visceral pain in rodents: neurochemical, hormonal, immune and epigenetic mechanisms

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dc.contributor.advisor Cryan, John F. en
dc.contributor.advisor Dinan, Timothy G. en Moloney, Rachel D. 2015-06-02T15:38:40Z 2015-06-02T15:38:40Z 2014 2014
dc.identifier.citation Moloney, R. 2014. Stress-induced visceral pain in rodents: neurochemical, hormonal, immune and epigenetic mechanisms. PhD Thesis, University College Cork. en
dc.description.abstract Visceral pain is a debilitating disorder which affects up to 25% of the population at any one time. It is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. Currently the treatment strategies are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. The work presented in this thesis aimed to redress this issue and look in more detail at the molecular mechanisms of visceral pain in preclinical models. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here a mouse model of early-life stress-induced visceral hypersensitivity was validated. Moreover, mouse strain differences were also apparent in visceral sensitivity suggesting a possible genetic component to the underlying pathophysiology. Furthermore, gender and sex hormones were also implicated in stress sensitivity and visceral pain. Using the rat model of maternal separation, some of the epigenetic mechanisms underpinning visceral hypersensitivity, specifically the contribution of histone acetylation were unravelled. Glutamate has been well established in somatic pain processing, however, its contribution to visceral pain has not been extensively characterised. It was found that glutamate uptake is impaired in viscerally hypersensitive animals, an effect which could be reversed by treatment with riluzole, a glutamate uptake activator. Moreover, negative modulation of the metabotropic glutamate (mGlu) receptor 7 was sufficient to reverse visceral hypersensitivity in a stress sensitive rat strain, the Wistar Kyoto rat. Furthermore, toll-like receptor 4 (TLR4) was implicated in chronic stress-induced visceral hypersensitivity. Taken together, these findings have furthered our knowledge of the pathophysiology of visceral pain. In addition, we have identified glutamate transporters, mGlu7 receptor, histone acetylation and TLR4 as novel targets, amenable to pharmacological manipulation for the specific treatment of visceral pain. en
dc.description.sponsorship Science Foundation Ireland (07/CE/B1368 and 12/RC/2273) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Rachel Moloney. en
dc.rights.uri en
dc.subject Stress en
dc.subject Rodent models en
dc.subject Glutamate en
dc.subject Epigenetic en
dc.subject Gender differences in pain sensitivity en
dc.subject Visceral pain en
dc.title Stress-induced visceral pain in rodents: neurochemical, hormonal, immune and epigenetic mechanisms en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en Indefinite 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en Alimentary Pharmabotic Centre en Psychiatry en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.embargoformat Not applicable en
dc.internal.conferring Summer Conferring 2014

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© 2014, Rachel Moloney. Except where otherwise noted, this item's license is described as © 2014, Rachel Moloney.
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