title: Intravesical hyaluronidase causes chronic cystitis in a rat model: a potential model of bladder pain syndrome/interstitial cystitis.
abstract: OBJECTIVE
  To determine whether a potential rat model of bladder pain syndrome could be developed through long-term intermittent intravesical hyaluronidase.
  
  
  METHODS
  A total of 64 female Sprague-Dawley rats were divided into a control group, a low-dose hyaluronidase (1 mg/mL) group, a high-dose hyaluronidase (4 mg/mL) group and a hyaluronic acid-treated group. Hyaluronidase was given intravesically three times a week for 1 month. Hyaluronic acid (0.5 mL, 0.8 mg/mL) was introduced intravesically to hyaluronidase-treated rats' bladders. Histological changes, cystometry, nociceptive behaviors, and messenger ribonucleic acid levels of inflammatory factors were evaluated and compared between groups.
  
  
  RESULTS
  All hyaluronidase-treated rats showed chronic inflammation and fibrosis, increased and activated mast cells, thinned bladder epithelium with abnormal expressions of uroplakin III and zonula occluden-1, and increased levels of interleukin-6 and intercellular adhesion molecule-1 messenger ribonucleic acid. However, the inflammatory score and levels of interleukin-6 and intercellular adhesion molecule-1 were more significant in the high-dose hyaluronidase group than in the low-dose hyaluronidase group (P < 0.01). Furthermore, hyaluronidase-treated rats showed markedly decreased intercontraction intervals, bladder capacity and increased sensitivity to pain compared with controls (P < 0.01). Hyaluronic acid treatment significantly decreased the inflammatory level, number of mast cells, sensitivity to pain, levels of interleukin-6 and intercellular adhesion molecule-1, and increased intercontraction intervals and bladder capacity (P < 0.01).
  
  
  CONCLUSIONS
  Long-term intermittent intravesical hyaluronidase could develop a severe chronic cystitis with diffused fibrosis accompanied by altered histology and bladder function. This chronic cystitis rat model can resemble the clinical and histopathological features of human bladder pain syndrome, and might be a potential valuable model for investigation of this troublesome disease.
authors.affiliation: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Urology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Yi Song
authors.initials: YS
authors.lastname: Lv
authors.forename: You Sheng
authors.initials: YS
authors.lastname: Yao
authors.forename: Lu
authors.initials: L
authors.lastname: Rong
authors.forename: Ming En
authors.initials: ME
authors.lastname: Lin
authors.forename: Bi Hua
authors.initials: BH
authors.lastname: Deng
authors.forename: Yun
authors.initials: Y
authors.lastname: Xie
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Tian Xin
authors.initials: TX
authors.lastname: Lin
authors.forename: Ke Wei
authors.initials: KW
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D002908:Chronic Disease; D003556:Cystitis / Q000139:chemically induced* / Q000473:pathology; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006821:Hyaluronoglucosaminidase; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006821:Hyaluronoglucosaminidase
keywords: animal model; bladder pain syndrome; cystitis; hyaluronidase; rat