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580: Prevention of neurogenic detrusor overactivity following spinal cord injury: Effects of early administration of resiniferatoxin and botulinum toxin A

Speaker
R. Oliveira, Porto (PT)
Authors
Oliveira R. 1 , Sousa Chambel S. 1 , Silva R. 1 , Coelho A. 1 , Cruz F. 2 , Duarte Cruz C. 1
Institutions
1Faculty of Medicine, University of Porto, Dept. of Biomedicine, Porto, Portugal, 2Hospital São João, Dept. of Urology, Porto, Portugal, 3
Event
33rd Annual EAU Congress Copenhagen
Date – time - Location
18 March 2018, 14:00 - 15:30, Green Area, Room 1 (Level 0)
Session
Poster Session 43 - Whats new from the bench: Treating or preventing LUTS
Topic
Functional LUTS, incontinence and neuro-urology: Basic science

Introduction & Objectives

Neurogenic detrusor overactivity (NDO) is a common problem in spinal cord injury (SCI) patients. It is characterized by periods of dangerously high intravesical pressures and frequent episodes of urinary incontinence. Currently, treatments are only initiated at later stages of disease progression, when NDO is fully established. Here we investigated if early administration of resiniferatoxin (RTX) and botulinum toxin A (BoNT/A) could prevent NDO.

Materials & Methods

Female rats were divided into 6 experimental groups.

Group Surgery Treatment
A (n=5) Sham No treatment
B (n=5) SCT Intravesical vehicle (ethanol 10% in saline), 3 and 9 days post-SCT
C (n=5) SCT Intravesical RTX 50 nM diluted in vehicle, 3 and 9 days post-SCT
D (n=5) SCT Intradetrusor injections of saline, 3 days post-SCT in 10 locations of bladder wall
E (n=5) SCT Intradetrusor BoNT/A 10U diluted in 100µL of saline, delivered as in group D
F (n=5) SCT Intradetrusor BoNT/A 25U diluted in 100µL of saline, delivered as in group D
Four weeks after surgery, animals underwent 1 hour-cystometry, followed by bladder tissue collection. Bladders were processed for Western blotting for the analysis of the expression of TRPV1, CGRP, GAP43, TH and VAChT.

Results

Four weeks after SCT, animals treated with vehicle/saline presented typical patterns of NDO. Early RTX administration significantly reduced peak pressure and amplitude of bladder contractions to values similar to those observed in group A. These effects were accompanied by a marked decrease in bladder expression of TRPV1, the molecular target of RTX, CGRP and GAP43. BoNT/A also affected bladder function, causing a slight reduction in peak pressure and a significant decrease in the amplitude of bladder contractions. Preliminary observations suggest that BoNT/A-induced improvements in urodynamics reflect changes in bladder expression of TRPV1, VAChT and TH.

  Sham (A) SCT + early vehicle (B) SCT + early RTX (C) SCT + early saline (D) SCT + early 10U BoNT/A (E) SCT + early 25U BoNT/A (F)
Frequency (voidings/min)  0.40±0.16  0.66±0.23  0.55±0.17*  0.86±0.16*  1.06±0.25*  0.69±0.27
Peak Pressure (cm H2O)  26.61±3.93  46.04±9.56****  32.70±4.61##  40.33±6.97*  38.89±7.86*  29.48±9.40
Amplitude (cm H2O)  22.12±4.76  35.98±9.81***  18.36±3.54####  30.54±4.17  18.11±5.84¥  14.12±4.43¥¥
Data is presented as mean±standard deviation, *p≤0.05, ***p≤0.001, ****p≤0.0001 compared to A; ##p≤0.01, ####p≤0.0001, compared to B; ¥p≤0.05, ¥¥p≤0.01 compared to D.

Conclusions

Early interventions with RTX and BoNT/A lead to significant improvements on bladder function in a rat model of NDO. RTX produced a more evident effect on the prevention of high intravesical pressures, suggesting that restricted modulation of bladder sensory afferents at early stages of disease progression could be used to prevent NDO.
Funding: SCML, NORTE2020