The expression of inflammatory mediators in bladder pain syndrome

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dc.contributor.authorOffiah, Ifeoma
dc.contributor.authorDidangelos, Athanasios
dc.contributor.authorDawes, John
dc.contributor.authorCartwright, Rufus
dc.contributor.authorKhullar, Vik
dc.contributor.authorBradbury, Elizabeth J.
dc.contributor.authorO'Sullivan, Suzanne
dc.contributor.authorWilliams, Dic
dc.contributor.authorChessell, Iain P.
dc.contributor.authorPallas, Kenny
dc.contributor.authorGraham, Gerry
dc.contributor.authorO'Reilly, Barry A.
dc.contributor.authorMcMahon, Stephen B.
dc.contributor.funderMedImmuneen
dc.contributor.funderAstraZenecaen
dc.contributor.funderImperial College Londonen
dc.contributor.funderInternational Urogynaecological Associationen
dc.contributor.funderMedical Research Councilen
dc.date.accessioned2019-10-30T05:57:04Z
dc.date.available2019-10-30T05:57:04Z
dc.date.issued2016-03-07
dc.description.abstractBackground: 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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationOffiah, 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.2016.02.058en
dc.identifier.doi10.1016/j.eururo.2016.02.058en
dc.identifier.eissn1873-7560
dc.identifier.endpage290en
dc.identifier.issn0302-2838
dc.identifier.issued2en
dc.identifier.journaltitleEuropean Urologyen
dc.identifier.startpage283en
dc.identifier.urihttps://hdl.handle.net/10468/8914
dc.identifier.volume70en
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.relation.urihttps://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.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAnimal modelen
dc.subjectBladder pain syndromeen
dc.subjectCCL21en
dc.subjectClinical correlationen
dc.subjectFGF7en
dc.subjectGene expression analysisen
dc.subjectInterstitial cystitisen
dc.subjectPain behaviouren
dc.titleThe expression of inflammatory mediators in bladder pain syndromeen
dc.typeArticle (peer-reviewed)en
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