title: Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome.
abstract: Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine.
  
  
  
  Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75NTR(p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay.
  
  
  
  Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75NTRin basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls.
  
  
  
  Sensory hyperinnervation and basal urothelial p75NTRstaining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress.
authors.affiliation: Department of Gynecology and Obstetrics, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland; Institute of Pathology, Medical University Graz (SR), Graz, Austria.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Regauer
authors.affiliation: Department of Gynecology and Obstetrics, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland; Institute of Pathology, Medical University Graz (SR), Graz, Austria. Electronic address: marianne.gamper@stgag.ch.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gamper
authors.affiliation: Department of Gynecology and Obstetrics, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland; Institute of Pathology, Medical University Graz (SR), Graz, Austria.
authors.forename: Mathias K
authors.initials: MK
authors.lastname: Fehr
authors.affiliation: Department of Gynecology and Obstetrics, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland; Institute of Pathology, Medical University Graz (SR), Graz, Austria.
authors.forename: Volker
authors.initials: V
authors.lastname: Viereck
mesh_terms: D000328:Adult; D000368:Aged; D001317:Austria; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D015331:Cohort Studies; D018856:Cystitis, Interstitial / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000652:urine; D011446:Prospective Studies; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013557:Switzerland; D016482:Urinalysis / Q000379:methods; D001743:Urinary Bladder / Q000294:innervation*; D053201:Urinary Bladder, Overactive / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor
keywords: cystitis; inflammation; innervation; interstitial; nerve growth factor; overactive; urinary bladder