Login to Access Video or Poster Abstract: MP26-10
Sources of Funding: None

Introduction

Pelvic surgery induced detrusor underactivity (DU) remains a poorly understood condition. Preganglionic pelvic nerve crush injury (PNI) in the rat has been described as a model for neurogenic DU. In this study we investigate temporal changes in detrusor contractility, detrusor fibrosis and denervation of the pelvic plexus as potential players in the pathophysiology of DU.

Methods

Male Sprague-Dawley rats (10-12w) underwent PNI 3x15s or sham surgery. One, three and nine weeks after surgery, functional and molecular assessments were planned. Detrusor contractility was examined in vitro in organ bath studies. Contractile responses tot KCl 120mM, cumulative doses of carbachol, non-cumulative doses of α,β-methylene ATP (mATP) and electrical field stimulation (EFS) were recorded. Gene expression was assessed by RT-qPCR. The genes evaluated in the bladder and major pelvic ganglion (MPG) were: vesicular acetylcholine transporter (VAchT), tyrosine hydroxylase (TH), protein gene product 9.5 (PGP9.5); and in the bladder: M2 and M3 muscarinic receptors, P2X1 purinergic receptor, collagen 1 and 3 and smoothelin. Statistical analyses were performed by one-way ANOVA with Tukey-Kramer post test.

Results

No changes were observed in contractile responses to KCl 120mM. One week after PNI, a 82% upregulation of collagen 1 was observed with a 77% reduction at 9 weeks (p<0,0001). Smoothelin expression was reduced by 45% 1 week after PNI with recovery at 9 weeks (p<0,0001), all compared to sham. _x000D_ Compared to sham, maximum contractile responses to carbachol and mATP were preserved at 3 and 9 weeks following PNI. Relative expression of M3 was increased at 3 (+59%) and 9 weeks (+46%) compared to sham (p=0,0002), but no differences were seen in M2 and P2X1 expression. _x000D_ Functional detrusor denervation was objectified by EFS: at 32 Hz contractile responses were reduced at 1 week (-40%), 3 weeks (-23%) and 9 weeks (-24%) after PNI compared to sham (p<0,0001). In the bladder, VAchT expression was 4 times less at 9 weeks (p=0,03), whereas TH expression was 76% lower 1 week following PNI with partial recovery at 9 weeks (p=0,0067), all compared to sham. Similarly, TH expression was 57% less in the MPG 1 week after PNI compared to sham with recovery at 9 weeks (p<0,0001). In the MPG, the expression of PGP9.5 was reduced following PNI compared to sham (p=0,002). _x000D_

Conclusions

Functional and molecular denervation of the bladder and MPG is observed in our rat model for neurogenic DU. However, the detrusor remains contractile to parasympathetic stimulation. Therefore, research should focus on optimizing neural regeneration of the pelvic plexus.

Funding

None