Acute Chemodenervation of the Bladder With Botulinum Toxin After Spinal Cord Injury Resulted in Preserved Bladder Function in Rodents.

Abstract

Despite modern bladder management methods, lower and upper urinary tract complications still contribute significantly to morbidity and diminished quality of life in persons with spinal cord injuries (SCI). Neurogenic overactive bladders often develop after SCI and this can result in loss of compliance, with concomitant urinary tract complications. Currently, there is no treatment available to prevent the development of neurogenic bladder.

Aims: In this study, we tested whether acute application of botulinum toxin A (BoNT-A) to the detrusor can limit the development of poorly compliant neurogenic bladders.

Methods: Rats sustained contusion type spinal cord injury at T8 and either received intradetrusor saline or BoNT-A injections immediately (acute) or at 4-weeks post injury (wpi)(chronic). Cystometry studies were performed at 6-8 wpi for all animals.

Results: We found that acute BoNT-A treatment after SCI resulted in animals normalized bladder capacity, improved compliance, and reduction in non-voiding contractions compared to control animals. Only acute BoNT-A treatment, but not chronic BoNT-A treatment, resulted in improving bladder compliance, retaining micturition reflexes, and reducing non-voiding contractions. These bladder physiological changes in acute BoNT-A treated SCI animals were accompanied by significant decreases in calcitonin gene related peptide (CGRP)-positive sensory fibers in the dorsal horn and growth associated protein (GAP)-43 expression, a marker for regenerating axons, compared to SCI animals.

Conclusions: Acute application of BoNT-A to the detrusor muscle after SCI can reduce pathophysiological bladder alterations and limits aberrant bladder afferent sprouting in the L5/S1 dorsal horn after SCI in a rat model.