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.

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.

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.

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.

Neurourology and urodynamics. 2019 Jun 10 [Epub ahead of print]

Raquel Oliveira, Ana Coelho, Filipa Franquinho, Mónica M Sousa, Francisco Cruz, Célia D Cruz

Department of Biomedicine, Experimental Biology Unit, Faculty of Medicine of Porto, University of Porto, Porto, Portugal., Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal., Translational NeuroUrology, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal.