Effects of early intravesical administration of resiniferatoxin to spinal cord-injured rats in neurogenic detrusor overactivity

Neurourol Urodyn. 2019 Aug;38(6):1540-1550. doi: 10.1002/nau.24032. Epub 2019 Jun 10.

Abstract

Objectives: To investigate if intravesical administration during spinal shock of resiniferatoxin (RTX), an ultrapotent desensitizing agonist of transient receptor potential vanilloid-1 (TRPV1), would silence TRPV1-expressing bladder afferents at an early stage of disease progression and modulate neurogenic detrusor overactivity (NDO) emergence.

Materials and methods: Rats submitted to largely incomplete spinal cord transection at T8/9 spinal segment were treated with intravesical RTX (50 nM) or its vehicle during spinal shock. Four weeks after spinal lesion, bladder-reflex activity was evaluated by cystometry under urethane anesthesia, after which the bladder, spinal cord, and dorsal root ganglia were collected and processed.

Results: We found improvements on bladder function several weeks after early intravesical RTX administration, including a marked decrease of intravesical pressures and amplitude of bladder contractions. Such strong long-lasting urodynamic effects resulted from the very potent desensitizing activity of RTX on peripheral terminals of sensory afferents, an effect restricted to the bladder.

Conclusion: Our results support that an early intervention with RTX could potentially attenuate NDO development and ensuing urinary incontinence, with a dramatic impact on the quality of life of spinal cord injury patients.

Keywords: afferent desensitization; bladder dysfunction; neurogenic detrusor overactivity; resiniferatoxin; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Animals
  • Calcitonin Gene-Related Peptide / biosynthesis
  • Diterpenes / administration & dosage
  • Diterpenes / therapeutic use*
  • Female
  • GAP-43 Protein / biosynthesis
  • Ganglia, Spinal / diagnostic imaging
  • Neurons, Afferent
  • Rats
  • Rats, Wistar
  • Reflex
  • Spinal Cord Injuries / complications*
  • Spinal Cord Injuries / physiopathology
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / biosynthesis
  • Urinary Bladder / innervation
  • Urinary Bladder / physiopathology
  • Urinary Bladder, Overactive / drug therapy*
  • Urinary Bladder, Overactive / etiology*
  • Urodynamics / drug effects

Substances

  • Diterpenes
  • GAP-43 Protein
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • resiniferatoxin
  • Calcitonin Gene-Related Peptide