Intravesical electromotive administration of botulinum toxin type A in improving the bladder and bowel functions: Evidence for novel mechanism of action

Abstract

Objective: To examine the hypothesis that what is the concomitant mechanism of action botulinum toxin type A (BoNTA) administration by intravesical electromotive into the bladder resulting in bladder function improvement. We also tried to confirm the possibility of retrograde trans-axonal transportation of toxin.Design: Animal study.Setting: Ten male rabbits were divided into two groups.Participants: Group 1 (G1) (n = 5) (BoNTA/EMDA), and group 2 (G2) (n = 5) the control group.Interventions: Animals in G1received 10 IU/Kg of intravesical BoNTA through a specific catheter for electromotive drug administration (BoNTA/EMDA). About 0.1-0.15 ml of toxin was diluted in 1 ml of distilled water. The maximum frequency of the device for drug solution delivery was set at 4 mA for 15 min. In G2 as the control group, the same procedure was performed to deliver normal saline to the bladder.Outcome measures: Multiple biopsies were taken from bladder's contiguous structures one month postoperatively. The immunohistochemical (IHC) evaluation was performed with anti-clostridium botulinum toxoid type A mouse IgM monoclonal antibody.Results: In specimens of G1, BoNTA penetrated through muscular layers of the bladder wall and the staining was uniform in the urothelium, interstitium, and muscular layers. Positive IHC staining showed that BoNTA was traced in the upper and lower spinal cord in addition to pelvic nerve, sacral nerve plexus, intestine wall, and pelvic floor muscle. In G2, all the specimens were intact in IHC staining.Conclusions: The presence of BoNTA in lower and upper spinal cord suggests the possibility of retrograde trans-axonal transfer of toxin to lower and upper neural pathways which may result in simultaneous improvement in bladder and bowel functions.

Keywords: Bladder; Botulinum toxin type A; Defecation; Immunohistochemistry; Urination.

Figure 1

IHC analysis in G1 revealed strong homogeneous BoNTA staining in (A) sacral nerve plexus (B) intestinal wall laid behind the posterolateral wall of the bladder, (C) upper spinal cord, (D) lower spinal cord, (E) pelvic nerve, and (F) pelvic floor muscle. H&E analysis in G2 in (G) sacral nerve plexus (H) intestinal wall laid behind the posterolateral wall of the bladder, (I) upper spinal cord, (J) lower spinal cord, (K) pelvic nerve, and (L) pelvic floor muscle.

Figure 2

H&E analysis in the negative control group in (A) sacral nerve plexus (B) intestinal wall laid behind the posterolateral wall of the bladder, (C) upper spinal cord, (D) lower spinal cord, (E) pelvic nerve, and (F) pelvic floor muscle.