ISOLATED TRIGONE ONABOTULINUMTOXINA INJECTION DOES NOT ADVERSELY CHANGE AMBULATORY VOIDING FUNCTION IN A RAT MODEL OF OVERACTIVE BLADDER

INTRODUCTION AND OBJECTIVES: OnabotulinumtoxinA (BTX) chemodenervation is an established third-line therapy for overactive bladder. The aim of our study was to further characterize the physiologic effect of various BTX injection distributions on ambulatory and cystometric voiding function in conscious awake rats. METHODS: Adult female rats (n=36) were divided into six groups. Treatment animals received injection of 7.5 units BTX (in 25-125 µL saline; 25 µL/aliquot): intact control, saline vehicle control, unilateral BTX, trigone BTX, posterior-lateral BTX, whole bladder BTX. Micturition frequency and volume were assessed using metabolic cages at baseline (day 0, 7) and following injection (day 14, 21, 28). Bladder function was then assessed using anesthetized acetic acid cystometry. RESULTS: There was no overall correlation between rat weight and mean voided volume (r = -0.02, p = 0.81). Small volume voids were significantly associated with increased food intake (r = -0.21, p = 0.006) and greater stool output (r = -0.23, p = 0.003). Mean nocturnal voided volume was similar in control, vehicle, trigone and posterior-lateral groups. The ability to void small volumes was preserved in both the control and treatment groups with the exception of unilateral and whole bladder injection which demonstrated increased minimum voided volumes. On cystometry, mean voided volume was the greatest in the control and trigone groups prior to acetic acid. Increased threshold pressure was noted in both unilateral and whole bladder injection groups. Post void residual was decreased in all groups after acetic acid. The lowest number of voids and longest interval between voids was noted after unilateral and whole bladder BTX injection. Cystometric intercontractile interval correlated with increased nocturnal mean voided volume before (r = 0.33, p = 0.05) and after (r = 0.24, p = 0.17) acetic acid. Cystometric mean voided volume correlated with ambulatory nocturnal voided volume, however was almost 10-fold lower after saline instillation (r = 0.18, p = 0.30), and more closely approximated ambulatory voiding after acetic acid instillation (r = 0.30, p = 0.08). CONCLUSIONS: Unilateral and whole bladder BTX injection resulted in elevated ambulatory nocturnal mean voided volumes, with higher pressure and smaller volume voids noted on cystometry. Trigone and posterior-lateral BTX injection patterns appear to preserve contractility, with threshold and peak contraction pressures similar to control animals