Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms

Abstract

Resiniferatoxin (RTX) and botulinum toxin subtype A (BTX-A) are increasingly viewed as potential treatments for lower urinary tract symptoms (LUTS) refractory to conventional therapy. RTX, a capsaicin analogue devoid of severe pungent properties, acts by desensitizing the transient receptor potential vanilloid type 1 (TRPV1) receptor and inactivating C-fibers. BTX-A cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in afferent and efferent nerve endings, therefore impeding the fusion of synaptic vesicles with the neuronal membrane necessary for the release of neurotransmitters. In patients with neurogenic and idiopathic detrusor overactivity, RTX and BTX-A have been shown to increase the volume to first detrusor contraction, increase bladder capacity, and improve urinary incontinence and quality of life. Recent data also suggest a role for these neurotoxins in treating urgency, the primary symptom in overactive bladder (OAB) syndrome. Furthermore, experimental data strongly support the use of both neurotoxins in the treatment of pain and frequency in patients with interstitial cystitis/painful bladder syndrome (IC/PBS), although the results from available clinical trials for this use are still inconclusive. In spite of promising results overall, it should be made clear that the administration of these neurotoxins is still considered an experimental procedure and that more clinical studies are necessary before a license for their use will be issued by health authorities.

Urothelial Signaling

“…Altered expression or sensitivity of molecular targets such as TRPV1, acid-sensing channels, and muscarinic receptors have been reported in BPS/IC patients as well as in animal models for the syndrome (82,124,140,249). In addition, augmented release of transmitters, most notably ATP, from the urothelium can lead to painful sensations by excitation of purinergic receptors on sensory fibers both peripherally and centrally (43,56,267).…”

“…In patients with NDO, there is a corresponding increase in NGF protein that is decreased or normalized with treatment with BoNT-A (115). As NGF has been shown to increase expression of a number of ion channels including TRPV1, it is not surprising that patients with neurogenic bladders exhibit increased urothelial-TRPV1 expression (82). Changes in TRPV1 expression were found to be normalized in patients responding favorably to intravesical vanilloid therapy (23).…”

Are Antimuscarinic Drugs Effective Against Urinary Frequency Mediated by Atropine-Resistant Contractions?

“…Attention is being focused increasingly on the role of atropine-resistant contractions in the treatment of urinary frequency and urgency due to OAB or neurogenic bladder and numerous studies have been conducted (27,28). In the clinical setting, intravesical resiniferatoxin or botulinum toxin A-injection therapy has been shown to be successful for the control of abnormal excitation of atropine-resistant contractions in patients with symptoms refractory to antimuscarinic drugs (29).…”

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Pathophysiology and Pharmacotherapy of Overactive Bladder

“…Vanilloid receptor agonists capsaicin and resiniferatoxin have proven efficacy but are associated with adverse events such as urinary retention, limiting their more widespread applicability (49). Botulinum toxin A, although not approved for use in OAB and detrusor overactivity in most countries, has a well-documented therapeutic effect in neurogenic detrusor overactivity, and it may also be useful for idiopathic detrusor overactivity.…”