title: Liposome Based Intravesical Therapy Targeting Nerve Growth Factor Ameliorates Bladder Hypersensitivity in Rats with Experimental Colitis.
abstract: Pelvic organ cross sensitization is considered to contribute to overlapping symptoms in chronic pelvic pain syndrome. Nerve growth factor over expression in the bladder is reportedly involved in the symptom development of bladder pain syndrome/interstitial cystitis. We examined whether a reduction of over expressed nerve growth factor in the bladder by intravesical treatment with liposome and oligonucleotide conjugates would ameliorate bladder hypersensitivity in a rat colitis model.
  
  
  
  Adult female rats were divided into 1) a control group, 2) a colitis-oligonucleotide group with intracolonic TNBS (2,4,6-trinitrobenzene sulfonic acid) enema and intravesical liposome-oligonucleotide treatments, 2) a colitis-saline group with intracolonic TNBS and intravesical saline treatments, 4) a sham oligonucleotide group with intravesical liposome-oligonucleotide treatment without colitis and 5) a sham-saline group with intravesical saline treatment without colitis. Liposomes conjugated with nerve growth factor antisense oligonucleotide or saline solution were instilled in the bladder and 24 hours later colitis was induced by TNBS enema. Effects of nerve growth factor antisense treatment were evaluated by pain behavior, cystometry, molecular analyses and immunohistochemistry 10 days after TNBS treatment.
  
  
  
  In colitis-oligonucleotide rats nerve growth factor antisense treatment ameliorated pain behavior and decreased a reduction in the intercontraction interval in response to acetic acid stimulation as well as nerve growth factor expression in the bladder mucosa. All were enhanced in colitis-saline rats compared to sham rats.
  
  
  
  Nerve growth factor over expression in the bladder mucosa and bladder hypersensitivity induced after colitis were decreased by intravesical application of liposome-oligonucleotide targeting nerve growth factor. This suggests that local antinerve growth factor therapy could be effective treatment of bladder symptoms in chronic pelvic pain syndrome.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawamorita
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kashyap
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Urology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: nyos@pitt.edu.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000150:complications*; D018856:Cystitis, Interstitial / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005260:Female; D008081:Liposomes; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000627:therapeutic use; D017699:Pelvic Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D020932:Nerve Growth Factor
keywords: irritable bowel syndrome; liposomes; nerve growth factor; pain; urinary bladder