title: The Expression of Inflammatory Mediators in Bladder Pain Syndrome.
abstract: Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life.
  
  
  
  We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London, UK; Department of Urogynaecology, Cork University Maternity Hospital, University College Cork, Wilton, Co. Cork, Ireland. Electronic address: ifeoma.offiah@uclh.nhs.uk.
authors.forename: Ifeoma
authors.initials: I
authors.lastname: Offiah
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London, UK.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Didangelos
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Dawes
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Rufus
authors.initials: R
authors.lastname: Cartwright
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Vik
authors.initials: V
authors.lastname: Khullar
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London, UK.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bradbury
authors.affiliation: Department of Urogynaecology, Cork University Maternity Hospital, University College Cork, Wilton, Co. Cork, Ireland.
authors.forename: Suzanne
authors.initials: S
authors.lastname: O'Sullivan
authors.affiliation: Neuroscience IMED, MedImmune, Cambridge, UK.
authors.forename: Dic
authors.initials: D
authors.lastname: Williams
authors.affiliation: Neuroscience IMED, MedImmune, Cambridge, UK.
authors.forename: Iain P
authors.initials: IP
authors.lastname: Chessell
authors.affiliation: The Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Kenny
authors.initials: K
authors.lastname: Pallas
authors.affiliation: The Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Gerry
authors.initials: G
authors.lastname: Graham
authors.affiliation: Department of Urogynaecology, Cork University Maternity Hospital, University College Cork, Wilton, Co. Cork, Ireland.
authors.forename: Barry A
authors.initials: BA
authors.lastname: O'Reilly
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000328:Adult; D000818:Animals; D054421:Chemokine CCL21 / Q000235:genetics*; D018856:Cystitis, Interstitial / Q000175:diagnosis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D010146:Pain / Q000175:diagnosis / Q000209:etiology / Q000276:immunology; D051381:Rats; D015398:Signal Transduction; D013223:Statistics as Topic; D063189:Symptom Assessment; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology
chemical_list: C515478:CCL21 protein, human; D054421:Chemokine CCL21; C496453:FGF7 protein, human; D018836:Inflammation Mediators; D051523:Fibroblast Growth Factor 7
keywords: Animal model; Bladder pain syndrome; CCL21; Clinical correlation; FGF7; Gene expression analysis; Interstitial cystitis; Pain behaviour