Detrusor HyperReflexia & Capsaicin

Objective
Resiniferatoxin (RTX), a substance isolated from some species of Euphorbia, a Cactus-like plant, shows pharmacological effects similar to those of Capsaicin.

We have studied the possibility of treating Detrusor HyperReflexia refractory to IntraVesical Capsaicin in patients with Chronic Spinal Cord Injuries, thereby providing insight into the mechanism of action of RTX on Sensory Neurons and its possible future pharmacological and clinical use.

Materials & Methods
TX saline solution (30 ml at a concentration of 10(-5) M) was instilled into the Bladder of 7 patients with Detrusor HyperReflexia, refractory to IntraVesical Capsaicin therapy, and left in place for 30 min.

Effects on Bladder Function were monitored during the treatment and at follow-up (15 days and 4 weeks later).

Results
Fifteen days after RTX, the mean CystoManometric Capacity increased significantly from 190 ml +/- 20 ml to 407.14 ml +/- 121.06 (p < 0.01), and it remained high four weeks later (421.66 +/- 74.40 p < 0.01).

After 15 days, four patients had a pharmacologically induced Detrusor Areflexia. They emptied their Bladders by clean Intermittent Catheterization. After four weeks, only two patients still had a pharmacologically induced Detrusor Areflexia.

Clinically, three patients remained dry, and the other three reported a significant improvement in their Incontinence and symptoms (Frequency, Urgency and Nocturia).

Conclusions
By interfering with Sensory UnMyelinated Fibers, Intravesical RTX seems to be a promising treatment option for selected cases of Detrusor HyperReflexia.

The ideal dosage and treatment interval have not yet been established, and further studies are necessary to confirm our preliminary results.

Purpose
Capsaicin Sensitive Primary Afferents (CSPA) have been implicated in the PathoGenesis of HyperReflexia after Spinalization. In this study we investigated the role of the efferent function of these fibers in Detrusor HyperReflexia and its effect on Detrusor physiology and pharmacology.

Materials & Methods
Four groups of female Sprague Dawley rats were included in our study. These groups were normal controls, Capsaicin treated normal rats, Spinalized rats and Capsaicin treated Spinalized rats.

Six weeks following Spinalization, animals were subjected to Cystometric Study, and Bladders were obtained for either in vitro Detrusor contractility study or Substance P (SP), Neurokinin A (NKA) and Calcitonin Gene Related Peptide (CGRP) quantification by RadioImmunoassay.

Results
Spinalized animals consistently developed HyperReflexia after Spinalization in the form of Uninhibited Contractions more than 15 cm. water in amplitude.

This was accompanied by increased Urinary Bladder total content of the Neuropeptides but without any change in the Detrusor contractility or Neurokinin Receptor pharmacology as shown by responses to KCl, electric field stimulation and Neurokinin Receptor Selective Agonists in the in vitro study.

the control group, Urinary Bladder total content of SP, NKA and CGRP was 0.19+/-0.03, 0.15+/-0.01 and 0.84+/-0.1 pmol/bladder respectively.

In contrast, in the spinalized animals, these were 0.44+/-0.07, 0.21+/-0.03 and 2.28+/-0.34 pmol/bladder for the same peptides, respectively. Capsaicin treatment abolished HyperReflexia, which corresponded with the decrease in the Neuropeptide content of the Urinary Bladder.

The number and amplitude of the uninhibited contractions decreased dramatically. SP, NKA and CGRP reached 0.06+/-0.01, 0.07+/-0.01 and 0.44+/-0.18 pmol/bladder 2 weeks after Capsaicin treatment in spinalized animals.

This was associated with the occurrence of Detrusor super-sensitivity to both Neurokinin Receptor Selective Agonists.

Conclusion
This study demonstrates the importance of the efferent function of the CSPA in the PathoGenesis of HyperReflexia. On the other hand, Detrusor changes were shown to be a noncrucial factor in the development of HyperReflexia.

Purpose
We studied the effect of Surface NeuroModulation on Cystometric Pressure and volume parameters in women with Detrusor Instability or Sensory Urgency.

Electrical current was delivered to the SupraPubic region and Third Sacral Foramina via a Transcutaneous Electrical Nerve Stimulator with Sham NeuroModulation control.

Materials & Methods
A consecutive series of women with proved Detrusor Instability or Sensory Urgency were randomized to 3 surface NeuroModulation groups. Volume and pressure parameters were the main outcomes of Transcutaneous Electrical Nerve Stimulation applied during second CystoMetric Fill.

Results
Sham Transcutaneous Electrical Nerve Stimulation did not alter the outcome measures. However, NeuroModulation delivered across the SupraPubic and Sacral skin effected a reduction in mean maximum height of Detrusor contraction.

A current which Inhibits Motor Activity was not superior to that which Inhibits Sensory Perception in reducing Detrusor pressure. Response in Sensory Urgency was poor.

Conclusions
Results from our sham controlled study suggest that short-term surface NeuroModulation via Transcutaneous Electrical Nerve Stimulation may have a role in the treatment of Detrusor Instability. Future studies must examine the clinical effect of long-term Surface NeuroModulation.

The aim of this study was to investigate the efficacy and tolerance of Capsaicin, a NeuroToxin for C-Fiber Afferents, applied IntraVesically in the treatment of Detrusor HyperReflexia.

Eleven male and nine female patients who had Spinal Cord lesions caused by Multiple Sclerosis (12) or Trauma (eight) resulting in Detrusor HyperReflexia with Urge Incontinence and Pollakiuria were randomized to receive one IntraVesical instillation of either 30 mg Capsaicin in 100 ml 30% Ethanol or 100 ml 30% Ethanol alone.

The patients were evaluated clinically (voiding diary) and Urodynamically (maximum CystoMetric capacity, maximum Detrusor pressure, first and normal desire to void) before and 30 days after the instillation.

On day 30, the 10 patients who received Capsaicin had significant decreases in 24-h voiding frequency from 9.3+/-6.1 to 6.7+/-3.8 (P=0.016) and leakages from 3.9+/-1.6 to 0.6+/-0.8 (P=0.0008); their maximum CystoMetric capacity increased from 169+/-68 to 299+/-96 ml (P=0.01) and maximum Detrusor pressure decreased from 77+/-24 to 53+/-27 cm H2O.

There were no significant changes in the control group. In seven subjects in each group, instillation triggered immediate side effects (Suprapubic Pain, Sensory Urgency, Flushes, Hematuria, Autonomic HyperReflexia) that resolved within 2 weeks.

Intravesical Capsaicin significantly improves clinical and urodynamic parameters of Detrusor HyperReflexia in Spinal Cord Injured patients.

Side effects are frequent, tolerable, and identical to those induced by 30% Ethanol alone.