The expression of inflammatory mediators in bladder pain syndrome

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dc.contributor.author Offiah, Ifeoma
dc.contributor.author Didangelos, Athanasios
dc.contributor.author Dawes, John
dc.contributor.author Cartwright, Rufus
dc.contributor.author Khullar, Vik
dc.contributor.author Bradbury, Elizabeth J.
dc.contributor.author O'Sullivan, Suzanne
dc.contributor.author Williams, Dic
dc.contributor.author Chessell, Iain P.
dc.contributor.author Pallas, Kenny
dc.contributor.author Graham, Gerry
dc.contributor.author O'Reilly, Barry A.
dc.contributor.author McMahon, Stephen B.
dc.date.accessioned 2019-10-30T05:57:04Z
dc.date.available 2019-10-30T05:57:04Z
dc.date.issued 2016-03-07
dc.identifier.citation Offiah, I., Didangelos, A., Dawes, J., Cartwright, R., Khullar, V., Bradbury, E. J., O'Sullivan, S., Williams, D., Chessell, I. P., Pallas, K., Graham, G., O’Reilly, B. A. and McMahon, S. B. (2016), 'The Expression of Inflammatory Mediators in Bladder Pain Syndrome', European Urology, 70(2), pp. 283-290. DOI: 10.1016/j.eururo.2016.02.058 en
dc.identifier.volume 70 en
dc.identifier.issued 2 en
dc.identifier.startpage 283 en
dc.identifier.endpage 290 en
dc.identifier.issn 0302-2838
dc.identifier.uri http://hdl.handle.net/10468/8914
dc.identifier.doi 10.1016/j.eururo.2016.02.058 en
dc.description.abstract Background: Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. Objective: We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Design, setting, and participants: Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. Outcome measures and statistical analysis: We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Results and limitations: Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Conclusions: Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. Patient summary: We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier B.V. en
dc.relation.uri https://www.sciencedirect.com/science/article/pii/S0302283816002487?via%3Dihub
dc.rights ©2016 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BYlicense (http://creativecommons.org/licenses/by/4.0/). en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Animal model en
dc.subject Bladder pain syndrome en
dc.subject CCL21 en
dc.subject Clinical correlation en
dc.subject FGF7 en
dc.subject Gene expression analysis en
dc.subject Interstitial cystitis en
dc.subject Pain behaviour en
dc.title The expression of inflammatory mediators in bladder pain syndrome en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Barry O'Reilly, Department of Urogynaecology, University College Cork, Cork, Ireland. +353-21-490-3000 Email:barry.oreilly@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder MedImmune en
dc.contributor.funder AstraZeneca en
dc.contributor.funder Imperial College London en
dc.contributor.funder International Urogynaecological Association en
dc.contributor.funder Medical Research Council en
dc.description.status Peer reviewed en
dc.identifier.journaltitle European Urology en
dc.internal.IRISemailaddress barry.oreilly@ucc.ie en
dc.identifier.eissn 1873-7560


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©2016 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BYlicense (http://creativecommons.org/licenses/by/4.0/). Except where otherwise noted, this item's license is described as ©2016 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BYlicense (http://creativecommons.org/licenses/by/4.0/).
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