Liposome-based Intravesical Therapy targeting Nerve Growth Factor (NGF) ameliorates Bladder Hypersensitivity in Rats with Experimental Colitis

PURPOSE - Pelvic organ cross sensitization is considered to contribute to overlapping symptoms in CPPS. Overexpression of NGF in the bladder is reportedly involved in the symptom development of BPS/IC patients.

This study examined whether a reduction of overexpressed NGF in the bladder by intravesical treatment with liposome and OND conjugates ameliorates bladder hypersensitivity in a rat colitis model.

MATERIALS AND METHODS - Adult female rats were divided into; (a) a control group, (b) a colitis-OND group with intracolonic TNBS enema and intravesical liposomal-OND treatments, (c) a colitis-saline group with intracolonic TNBS and intravesical saline treatments, (d) a sham-OND group with intravesical liposomal-OND treatment without colitis and (e) a sham-saline group with intravesical saline treatment without colitis. Liposomes conjugated with NGF antisense OND or saline solution were instilled into the bladder, and 24 hours later, colitis was induced by TNBS enema. Effects of NGF antisense treatment were evaluated by pain behavior, cystometry, molecular analyses and immunohistochemistry 10 days after TNBS treatment.

RESULTS - In colitis-OND rats, the NGF antisense treatment ameliorated pain behavior, and decreased a reduction in intercontraction intervals in response to acetic acid stimulation as well as NGF expression in the bladder mucosa, which were all enhanced in colitis-saline rats compared to sham rats.

CONCLUSIONS - NGF overexpression in the bladder mucosa and bladder hypersensitivity induced after colitis were reduced by intravesical application of liposomal OND targeting NGF, suggesting that the local anti-NGF therapy could be effective for the treatment of bladder symptoms in CPPS.

The Journal of urology. 2016 Jan 09 [Epub ahead of print]

Naoki Kawamorita, Satoru Yoshikawa, Mahendra Kashyap, Pradeep Tyagi, Yoichi Arai, Michael B Chancellor, Naoki Yoshimura

Department of Urology, University of Pittsburgh School of Medicine, Suite 700, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA; Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. , Department of Urology, University of Pittsburgh School of Medicine, Suite 700, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. , Department of Urology, University of Pittsburgh School of Medicine, Suite 700, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. , Department of Urology, University of Pittsburgh School of Medicine, Suite 700, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. , Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. , Department of Urology, Oakland University William Beaumont School of Medicine, Royal Oak, MI 48073, USA. , Department of Urology, University of Pittsburgh School of Medicine, Suite 700, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. 

PubMed

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