Central inhibitory effect of intravesically applied botulinum toxin A in chronic spinal cord injury

Neurourol Urodyn. 2011 Sep;30(7):1376-81. doi: 10.1002/nau.21068. Epub 2011 Apr 20.

Abstract

Aims: We evaluated a putative central inhibitory effect of intravesical botulinum toxin A (BoNT-A) on the activity of lumbosacral spinal neurons in a chronic spinal cord injury (SCI) model of bladder overactivity.

Methods: Female Sprague-Dawley rats underwent T8 spinal cord transection. Four weeks later, once overactive neuropathic detrusor pathways had developed, the animals underwent intravesical instillation with either saline (1 ml) or BoNT-A (Botox®, 20 U/1 ml) for 1 hr. Two days later, the rats then completed a cystometric evaluation prior to spinal cord harvest. Sections from the L4-S1 spinal cord segments were examined for the total number of c-fos immunoreactive cells.

Results: Comparison of the saline and BoNT-A treated groups showed a significant decrease in L6 (i.e., 67%, P < 0.001) and S1 (i.e., 47%, P < 0.01) c-fos expression (43%) in BoNT-A treated rats compared to saline controls. Cystometrogram studies revealed that the frequency of non-voiding bladder contractions was reduced by 73% (P < 0.05) in BoNT-A compared to saline treated rats. No change in the frequency of voiding bladder contractions or amplitude of bladder contraction was observed between the saline and BoNT-A treated groups.

Conclusion: In a SCI model of bladder overactivity, intravesical BoNT-A significantly inhibits the response of bladder afferent activated lumbosacral neurons without significantly impairing efferent bladder function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intravesical
  • Animals
  • Botulinum Toxins, Type A / administration & dosage*
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • Muscle Contraction / drug effects
  • Neural Inhibition / drug effects*
  • Neuromuscular Agents / administration & dosage*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / complications*
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology
  • Spinal Nerves / drug effects*
  • Spinal Nerves / metabolism
  • Spinal Nerves / physiopathology
  • Time Factors
  • Urinary Bladder / innervation*
  • Urinary Bladder, Overactive / drug therapy*
  • Urinary Bladder, Overactive / etiology
  • Urinary Bladder, Overactive / physiopathology
  • Urodynamics / drug effects

Substances

  • Neuromuscular Agents
  • Proto-Oncogene Proteins c-fos
  • Botulinum Toxins, Type A