An investigation into mechanisms of visceral pain in rodents

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dc.contributor.advisor O'Mahony, Siobhain M. en
dc.contributor.advisor Cryan, John F. en Felice, Valeria D. 2015-06-22T15:39:31Z 2014 2014
dc.identifier.citation Felice, V. 2014. An investigation into mechanisms of visceral pain in rodents. PhD Thesis, University College Cork. en
dc.description.abstract Visceral pain is a debilitating symptom of irritable bowel syndrome (IBS), a disorder affecting up to 30% of adults. A better understanding of the mechanisms underlying visceral hypersensitivity may facilitate development of more targeted therapies, improving the quality of life of these individuals. The studies performed in this thesis were designed to investigate important factors of visceral pain, including early-life manipulations, genetic predisposition and sex hormones. Maternal separation (MS) consistently reproduces visceral hypersensitivity and altered anxiety-like behaviours in rats, symptoms associated with IBS. It has been found that 5-HT2B receptor antagonism blocks visceral pain but no difference in relative 5-HT2B receptor mRNA expression was found in hippocampus, amygdala and colon. The neuronal activation patterns of prefrontal cortex and amygdala of MS rats were then investigated. MS animals are characterised by differential activation of the prefrontal cortex (anterior cingulate cortex (ACC), infralibic cortex, prelimbic cortex) as well as the central nucleus of the amygdala (CeA). Genetic factors also contribute to pain syndromes such as IBS. We utilised the Wistar Kyoto (WKY) rat, a stress-sensitive strain, as an animal model of brain-gut axis dysfunction. WKY rats have a lower expression of the glutamate transporter EAAT2 and mGlu4 receptor in the ACC. Another early-life factor that can increase susceptibility to functional gastrointestinal symptoms later life is disruption of the gut microbiota, thus early-life antibiotic treatment was used to assess this effect. Antibiotic treatment induced visceral hypersensitivity in adulthood and may be related to observed reductions in spinal cord alpha-2A adrenoreceptor (adra2A) mRNA. Lastly, we investigated sex differences in visceral sensitivity. EAAT1 & 2 mRNA levels are lower in females, potentially increasing glutamatergic concentration at the symaptic level. Moreover, NR1 and NR2B subunits mRNA of NMDA receptor were increased in caudal ACC of females. These findings may account for sex differences in visceral sensitivity. en
dc.description.sponsorship Irish Research Council for Science Engineering and Technology (EMBARK PG: (R13759)) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Valeria Felice. en
dc.rights.uri en
dc.subject Visceral pain en
dc.subject Preclinical models en
dc.subject Irritable bowel syndrome en
dc.subject Brain-gut-microbiome axis en
dc.subject Gender differences en
dc.title An investigation into mechanisms of visceral pain in rodents 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 en 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Irish Research Council for Science, Engineering and Technology en
dc.description.status Not peer reviewed en Anatomy 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, Valeria Felice. Except where otherwise noted, this item's license is described as © 2014, Valeria Felice.
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