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.
Female rats were divided into 6 experimental groups.
|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 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)|
|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¥¥|
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