Functional and molecular characterisation of the bilateral pelvic nerve crush injury rat model for neurogenic detrusor underactivity

Objectives To create a rat model for neurogenic detrusor underactivity (DU) by bilateral pelvic nerve crush injury (BPNI) and to study temporal changes in detrusor contractility and morphology. Materials and Methods Male Sprague-Dawley rats were subjected to BPNI or sham surgery and evaluated at 1, 3 and 9 weeks after surgery. Bladder function was determined in vivo by awake cystometry, micturition pattern analysis, and 24-h urine collection. Bladders were harvested for in vitro pharmacological investigation by isometric tension recording. Bladders and major pelvic ganglia were investigated by quantitative reverse transcription-polymerase chain reaction and histochemistry. Results Overflow incontinence was observed at 1 week after BPNI. At 3 and 9 weeks after BPNI, rats showed a bladder phenotype characteristic for DU with increased post-void residual urine volumes, reduced voiding efficiencies, and lower maximum pressures. In isolated bladder strips, contractile responses to KCl, carbachol, and alpha,beta-methylene adenosine 5 '-triphosphate (alpha,beta-mATP) were preserved. On the other hand, neural-induced contractility was reduced after BPNI, in line with reduced expression of protein gene product 9.5 and choline acetyltransferase in the major pelvic ganglion at 1 week after BPNI. The bladder-to-body weight ratio and detrusor thickness increased after BPNI, indicating detrusor hypertrophy to compensate for the reduced neural input. Conclusions BPNI induces a rat model for neurogenic DU. In this model, the detrusor maintains its contractility but denervation of the detrusor was observed.