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AND OBJECTIVES: The etiology of detrusor underactivity/underactive bladder (DU/UAB) is thought to be multifactorial, and functional damage of afferent and efferent nerves that innervate the bladder has been proposed as a pathophysiological basis of DU/UAB. We have shown previously that the rat with bilateral pelvic nerve crush (PNC) can be used as an animal model of UAB. This study was performed to further understand the mechanism of action of this model, specifically focusing on changes in bladder afferent function. METHODS: Female Sprague-Dawley rats were divided into two groups: bilateral PNC (n1⁄45) and control (n1⁄44). Under isoflurane anesthesia, lower midline laparotomy was performed and bilateral pelvic nerves proximal to major pelvic ganglia were exposed. Control rats underwent a sham operation where pelvic nerves were exposed but not crushed. A separate group of 5 rats underwent bilateral PNC. A straight Jacobson micro mosquito clamp was used to crush each pelvic nerve for 1 minute. At 2 weeks following PNC, the rats underwent awake continuous cystometry using a PE50 transvesical catheter and an infusion rate of 0.04 ml/min using either normal saline or 0.5% acetic acid. Data were collected using PowerLab system. Statistical comparisons between groups were performed using one-way ANOVA followed by Mann-Whitney unpaired t-test with Prism software. RESULTS: Following bilateral PNC, cystometry revealed that the intercontraction interval (ICI) and bladder capacity were significantly increased (p<0.05) compared to the control rats. Also, PVR increased (p<0.05) and voiding efficiency decreased (p<0.01) in the bilateral PNC group compared to the control group. When bladder afferent pathways were stimulated by switching from saline to 0.5% acetic acid infusion for cystometry, the control rats showed significant reductions (P<0.05) in ICI and bladder capacity; however, cystometric parameters including ICI and bladder capacity were not affected by acetic acid infusion in the bilateral PNC rats. CONCLUSIONS: This rat model of DU/UAB induced by bilateral PNC shows reduced responses to chemical irritation of bladder afferent pathways, suggesting that this model produces afferent nerve damage, which has been proposed as one of the underlying mechanisms of DU/UAB. Therefore, this study provides proof of concept that an afferent approach could be useful to treat DU/UAB due to denervation.

MP30-10 REDUCED AFFERENT SENSITIVITY IN THE RAT BILATERAL PELVIC NERVE CRUSH MODEL OF DETRUSOR UNDERACTIVITY