Intravesical resiniferatoxin for patients with neurogenic detrusor overactivity

Abstract

Background : Resiniferatoxin (RTX), a substance isolated from some species of Euphobia, is a specific C-fiber neurotoxin which produces desensitization rather than excitation. At first, we performed intravesical RTX therapy on eight patients with neurogenic detrusor overactivity. After we confirmed the safety and efficacy, a Japanese RTX study group was organized and a new protocol made. The multicenter trial was performed in Japan. However, the efficacy of the treatments was different among the institutions. Therefore, we have compared the results between the first protocol and the new one at our hospital. Methods : The first and second protocol involved the RTX solution (30 mL of 500 nM, and 100 mL of 1 m M, respectively) being instillated in the bladder for 30 min by almost the same procedures. Effects on bladder function were evaluated during treatment and at follow up.Results : For the first and second protocols, six out of eight patients noted symptomatic improvement while two patients did not notice any change in the degree of incontinence for one month. The mean urodynamic bladder capacity had significantly increased from 138.0 ± 64.4 mL to 227.3 ± 112.4 mL and 133.1 ± 43.3 mL to 247.0 ± 102.3 mL 1 month after RTX treatment for the first and second protocols, respectively ( P < 0.05). No severe side-effects were seen in either group. Conclusion : Intravesical RTX improved bladder capacity in patients with neurogenic detrusor overactivity in both protocols. The concentration of RTX did not exhibit any change in the effect and safety in our hospital. Intravesical RTX is a promising treatment for neurogenic detrusor overactivity.

Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder

“…Moreover, many articles have already reported the efficacy of RTX or capsaicin treatment for patients with neurogenic DO due to spinal cord diseases. [23][24][25][26] The results of the present study might suggest that urinary NGF levels were increased in the patients who might be effective to RTX treatment.…”

Effect of the intravesical resiniferatoxin instillation evaluated by the ice provocative urodynamic study

“…Watanabe et al 26 supposed that more than a 50 nM concentration of resiniferatoxin was favorable for a therapeutic effect. In recent studies, 9,18,27 resiniferatoxin, as low as 100 nmol/l (compared with 1 mmol/l capsaicin), induced full desensitization and was much less irritating to the bladder afferents.…”

Protein kinase C contributes to abnormal capsaicin responses in DRG neurons from cats with feline interstitial cystitis

“…Bladder pain and hyperactivity can be induced by activation of capsaicin (CAPS)-sensitive, unmyelinated (C-type) afferent nerves [7,18,20]. Intravesical administration of CAPS induces bladder pain; whereas desensitization of C-fiber bladder afferents with intravesical administration of resiniferatoxin, an ultrapotent CAPS analog, has been reported to reduce bladder overactivity [18].…”

“…Intravesical administration of CAPS induces bladder pain; whereas desensitization of C-fiber bladder afferents with intravesical administration of resiniferatoxin, an ultrapotent CAPS analog, has been reported to reduce bladder overactivity [18]. The CAPS sensitivity of C-fiber afferent nerves is conferred by the presence of a temperature-acid sensing receptor called the transient receptor potential vanilloid receptor 1 (TRPV1) [6,10].…”

“…A comparable disorder, feline interstitial cystitis (FIC), has been identified in domestic cats [3,4]. Previous studies revealed an increased density of peptidergic afferent nerves in the bladders of FIC cats suggesting that an abnormality of afferent pathways might contribute to the disorder [5,12].Bladder pain and hyperactivity can be induced by activation of capsaicin (CAPS)-sensitive, unmyelinated (C-type) afferent nerves [7,18,20]. Intravesical administration of CAPS induces bladder pain; whereas desensitization of C-fiber bladder afferents with intravesical administration of resiniferatoxin, an ultrapotent CAPS analog, has been reported to reduce bladder overactivity [18].…”