In vivo effects of botulinum toxin A on visceral sensory function in chronic spinal cord-injured rats

Objectives. To analyze the in vivo effects of botulinum toxin type A (BTX-A) on visceral sensory function in chronic spinal cord-injured (SCI) rats. Methods. One group of rats underwent spinal cord transection at the T8-T9 level (SCI) and the other group was left untreated. In 21 days, baseline open cystometrography (CMG) was performed. The rats were then treated intravesically with either 1 mL of 1% protamine sulfate (PS) to increase urothelial permeability or saline, followed by either 1 mL of BTX-A (20 U) or saline. CMG was repeated 48 hours after instillation, and any changes in the bladder contraction frequency and amplitude were evaluated. Results. After the instillation of PS and BTX-A or BTX-A alone, the bladder contraction frequency was significantly decreased in the SCI rats compared with the control rats (P <0.05); no change was seen in the contraction amplitude. When normal rats were given intravesical PS and/or BTX-A, or SCI animals were treated with PS alone, neither the frequency nor the amplitude of the contractions was affected. Also, no significant differences were found in the bladder contraction frequency or amplitude of contractions in any animal treated with instillation of saline alone. Conclusions. Intravesical BTX-A inhibits bladder sensory mechanisms by reducing the frequency of bladder contractions in an SCI rat model. Furthermore, our results suggest that intravesically applied BTX-A does not penetrate to the smooth muscle layer even after PS disruption of the bladder urothelium. These findings may have important clinical applications in treating overactive bladders after SCI.