resiniferatoxin and Urinary-Bladder--Overactive

Resiniferatoxin (RTX) is an ultrapotent capsaicin analog with a unique spectrum of pharmacological actions. The therapeutic window of RTX is broad, allowing for the full desensitization of pain perception and neurogenic inflammation without causing unacceptable side effects. Intravesical RTX was shown to restore continence in a subset of patients with idiopathic and neurogenic detrusor overactivity. RTX can also ablate sensory neurons as a "molecular scalpel" to achieve permanent analgesia. This targeted (intrathecal or epidural) RTX therapy holds great promise in cancer pain management. Intra-articular RTX is undergoing clinical trials to treat moderate-to-severe knee pain in patients with osteoarthritis. Similar targeted approaches may be useful in the management of post-operative pain or pain associated with severe burn injuries. The current state of this field is reviewed, from preclinical studies through veterinary medicine to clinical trials.

Topics: Diterpenes; Humans; Pain; Precision Medicine; TRPV Cation Channels; Urinary Bladder, Overactive

The bladder is an organ rich in vanilloid targets: dense unmyelinated c-fibers partially responsible for bladder sensation and response to noxious stimuli. Drugs such as capsaicin and resiniferatoxin (RTX) interact with the VR1 vanilloid receptor subtype to initially excite then subsequently desensitize the c-fibers. This chapter examines the literature describing the use of vanilloid receptor agonists in the treatment of the following urological disorders: neurogenic bladder (NGB), overactive bladder (OAB), and interstitial cystitis/painful bladder syndrome (IC/PBS). Review of the literature was performed using Pubmed and the following key words "capsaicin," "resiniferatoxin (RTX)," and "neurogenic bladder," "overactive bladder (OAB)," and "interstitial cystitis," "painful bladder syndrome." Articles focusing on randomized trials comparing intravesical administration of a vanilloid receptor agonist to placebo and those in English were reviewed. We conclude that capsaicin and RTX do appear to provide some acceptable treatment results in patients with neurogenic bladder, though larger studies are needed to confirm this. Although efficacy has been shown in some studies, currently the use of vanilloids cannot be recommended for routine use in patients with OAB as the need for catheterization may cause the risk to outweigh the benefit of treatment. Similarly, for the treatment of BPS, vanilloid receptor agonists lack strong evidence for efficacy or tolerability; larger studies are needed to define their role. Understanding how vanilloids are able to impact these disorders, however, may help further elucidate their underlying pathophysiological processes.

Topics: Capsaicin; Cystitis, Interstitial; Diterpenes; Humans; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

While Resin-iferatoxin (RTX) has been widely used for patients with storage lower urinary tract symptoms (LUTS), its clinical efficiency hasn't yet been well evaluated. A meta-analysis was performed to evaluate the exact roles of intravesical RTX for the treatment of storage LUTS in patients with either interstitial cystitis (IC) or detrusor overactivity (DO).. A meta-analysis of RTX treatment was performed through a comprehensive search of the literature. In total, 2,332 records were initially recruited, 1,907 from Elsevier, 207 from Medline and 218 from the Web of Science. No records were retrieved from the Embase or Cochrane Library. Seven trials with 355 patients were included and one trial was excluded because of the lack of extractable data. The analyses were all performed using RevMan 5.1 and MIX 2.0.. Bladder pain was significantly reduced after RTX therapy in patients with either IC or DO. The average decrease of the visual an alogue pain scale was 0.42 after RTX treatment (p = 0.02). The maximum cystometric capacity (MCC) was significantly increased in patients with DO (MCC increase, 53.36 ml, p = 0.006) but not in those with IC (MCC increase, -19.1 ml, p = 0.35). No significant improvement in urinary frequency, nocturia, incontinence or the first involuntary detrusor contraction (FDC) was noted after RTX therapy (p = 0.06, p = 0.52, p = 0.19 and p = 0.41, respectively).. RTX could significantly reduce bladder pain in patients with either IC or DO, and increase MCC in patients with DO; however, no significant improvement was observed in frequency, nocturia, incontinence or FDC. Given the limitations in the small patient size and risk of bias in the included trials, great caution should be taken when intravesical RTX is used before a large, multicenter, well-designed random control trial with a long-term follow-up is carried out to further assess the clinical efficacy of RTX in in patients with storage LUTS.

Topics: Administration, Intravesical; Adult; Cystitis, Interstitial; Diterpenes; Female; Humans; Lower Urinary Tract Symptoms; Male; Nocturia; Pain Measurement; Publication Bias; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urodynamics

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.

Topics: Animals; Botulinum Toxins, Type A; Chronic Disease; Cystitis; Diterpenes; Humans; Neuromuscular Agents; Urinary Bladder, Overactive

Refractory neurogenic detrusor overactivity refers to the clinical condition that is no longer manageable by anticholinergic therapy. This condition represents a formidable task to caregivers because the treatment of urinary incontinence and adequate protection of the upper urinary tract become extremely difficult. Treatment options for refractory neurogenic detrusor overactivity include detrusor injections of botulinum toxin and intravesical instillation of vanilloid compounds, mainly resiniferatoxin, or anticholinergic drugs. If these options fail, bladder augmentation or sacral anterior root stimulation offers excellent outcomes, although at much higher costs and risks to the patients.

Topics: Botulinum Toxins, Type A; Cholinergic Antagonists; Diterpenes; Humans; Neuromuscular Agents; Neurotoxins; Treatment Failure; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

To assess the hypothesis that resiniferatoxin (RTX) can be useful in women with urgency incontinence and idiopathic detrusor overactivity (IDO), we conducted a prospective, double-blind, randomized, placebo-controlled, parallel trial comparing the effects of RTX and placebo.. Fifty-eight patients were randomly assigned to receive a single intravesical dose of 100 ml of either RTX 50 nM or placebo. Safety and efficacy were evaluated over 4 weeks. The primary efficacy endpoints were voiding symptoms evaluated through the voiding diary. Secondary efficacy endpoint was urodynamic response. Quality of life was measured by the Kings' Health Questionnaire. Although improving trends were seen in both groups after the instillations, no statistically significant differences were found between the groups in any of the clinical or urodynamic parameters. RTX instillations were well tolerated with few and self-limited side-effects.. A single 50 nM intravesical dose of RTX was not better than placebo for the treatment of women with IDO and urgency incontinence.

Topics: Administration, Intravesical; Diterpenes; Double-Blind Method; Emotions; Female; Humans; Neurotoxins; Placebos; Quality of Life; Social Behavior; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urination

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.

Topics: Administration, Intravesical; Animals; Calcitonin Gene-Related Peptide; Diterpenes; Female; Ganglia, Spinal; GAP-43 Protein; Neurons, Afferent; Rats; Rats, Wistar; Reflex; Spinal Cord Injuries; TRPV Cation Channels; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics

Topics: Botulinum Toxins, Type A; Capsaicin; Diterpenes; Humans; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

We investigated the effects of replication-defective herpes simplex virus (HSV) vector expression of interleukin-4 (IL-4) on bladder overactivity and nociception. HSV vector expressing murine interleukin-4 (S4IL4) or the control vector expressing β-galactosidase (SHZ) were injected to the rat bladder wall. At 1 week after viral injection, in cystometry performed under urethane anesthesia, the S4IL4-treated group did not show the intercontraction intervals reduction during intravesical administration of 10 nM resiniferatoxin (RTx). At 2 weeks after viral injection, behavioral studies were performed on vector-injected animals in an awakened state. Freezing behavior induced by 3 μM RTx, administered for 1 min into the bladder, was significantly suppressed in the S4IL4 group compared with the SHZ group. Murine IL-4 levels examined by ELISA were significantly increased in bladder and bladder afferent dorsal root ganglia at 2 weeks after viral injection. The expression of IL-1β and IL-2 and bladder inflammatory responses were significantly suppressed in the RTx-irritated bladder of S4IL4-injected rats. These results indicate that HSV vector-mediated interleukin-4 expression in the bladder and bladder afferent pathways reduces the inflammatory response, bladder overactivity and nociceptive behavior induced by bladder irritation in the rat model. Therefore, IL-4 gene therapy could be a new strategy for treating urinary frequency and/or bladder pain.

Topics: Animals; Diterpenes; Female; Freezing Reaction, Cataleptic; Ganglia, Spinal; Gene Expression; Genetic Therapy; Genetic Vectors; Inflammation; Interleukin-4; Nociception; Rats; Rats, Sprague-Dawley; Simplexvirus; Urinary Bladder; Urinary Bladder, Overactive

We previously reported the effects of herpes simplex virus (HSV) vector-mediated enkephalin on bladder overactivity and pain. In this study, we evaluated the effects of vHPPE (E1G6-ENK), a newly engineered replication-deficient HSV vector encoding human preproenkephalin (hPPE). vHPPE or control vector was injected into the bladder wall of female rats 2 weeks prior to the following studies. A reverse-transcription PCR study showed high hPPE transgene levels in L6 dorsal root ganglia innervating the bladder in the vHPPE group. The number of freezing behaviors, which is a nociceptive reaction associated with bladder pain, was also significantly lower in the vHPPE group compared with the control group. The number of L6 spinal cord c-fos-positive cells and the urinary interleukin (IL)-1β and IL-6 levels after resiniferatoxin (RTx) administration into the bladder of the vHPPE group were significantly lower compared with those of the control vector-injected group. In continuous cystometry, the vHPPE group showed a smaller reduction in intercontraction interval after RTx administration into the bladder. This antinociceptive effect was antagonized by naloxone hydrochloride. Thus, the HSV vector vHPPE encoding hPPE demonstrated physiological improvement in visceral pain induced by bladder irritation. Gene therapy may represent a potentially useful treatment modality for bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis.

Topics: Analgesics; Animals; Diterpenes; Enkephalins; Female; Ganglia, Spinal; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Interleukin-1beta; Interleukin-6; Naloxone; Nociception; Protein Precursors; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Simplexvirus; Urinary Bladder; Urinary Bladder, Overactive; Urinary Catheterization; Virus Replication; Visceral Pain

Glycine is a major inhibitory neurotransmitter in the spinal cord, the concentration of which is regulated by two types of glycine transporters (GlyTs): GlyT1 and GlyT2. We hypothesized that the inhibition of GlyTs could ameliorate bladder overactivity and/or pain sensation in the lower urinary tract.. Investigate the effects of GlyT inhibitors on bladder overactivity and pain behavior in rats.. Cystometry was performed under urethane anesthesia in cyclophosphamide (CYP)-treated rats. In behavioral studies using conscious rats, nociceptive responses were induced by intravesical administration of resiniferatoxin (3μM). Selective GlyT1 or GlyT2 inhibitors were administered intrathecally to evaluate their effects.. Cystometric parameters, nociceptive behaviors (licking and freezing), and messenger RNA (mRNA) levels of GlyTs and glycine receptor (GlyR) subunits in the dorsal spinal cord (L6-S1) were measured.. During cystometry in CYP-treated rats, significant increases in intercontraction interval and micturition pressure threshold were elicited by ALX-1393, a selective GlyT2 inhibitor, but not by sarcosine, a GlyT1 inhibitor. These effects were completely reversed by strychnine, a GlyR antagonist. ALX-1393 also significantly suppressed nociceptive behaviors in a dose-dependent manner. In sham rats, GlyT2 mRNA was expressed at a much higher level (23-fold) in the dorsal spinal cord than GlyT1 mRNA. In CYP-treated rats, mRNA levels of GlyT2 and the GlyR α1 and β subunits were significantly reduced.. These results indicate that GlyT2 plays a major role in the clearance of extracellular glycine in the spinal cord and that GlyT2 inhibition leads to amelioration of CYP-induced bladder overactivity and pain behavior. GlyT2 may be a novel therapeutic target for the treatment of overactive bladder and/or bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis.

Topics: Animals; Diterpenes; Female; Freezing Reaction, Cataleptic; Glycine Agents; Glycine Plasma Membrane Transport Proteins; Nociceptive Pain; Pain; Rats; Rats, Sprague-Dawley; Sarcosine; Serine; Spinal Cord; Strychnine; Urinary Bladder, Overactive; Urination

Chronic pelvic pain of unknown etiology is a common clinical condition and may develop as a result of cross-sensitization in the pelvis when pathological changes in one of the pelvic organs result in functional alterations in an adjacent structure. The aim of the current study was to compare transient receptor potential vanilloid 1 (TRPV1) activated pathways on detrusor contractility in vivo and in vitro using a rat model of pelvic organ cross-sensitization. Four groups of male Sprague-Dawley rats (N = 56) were included in the study. Animals received intracolonic saline (control), resiniferatoxin (RTX, TRPV1 agonist, 10(-7) M), 2,4,6-trinitrobenzene sulfonic acid (TNBS, colonic irritant), or double treatment (RTX followed by TNBS). Detrusor muscle contractility was assessed under in vitro and in vivo conditions. Intracolonic RTX increased the contractility of the isolated detrusor in response to electric field stimulation (EFS) by twofold (P ≤ 0.001) and enhanced the contractile response of the bladder smooth muscle to carbachol (CCh). Acute colonic inflammation reduced detrusor contractility upon application of CCh in vitro, decreased bladder capacity by 28.1% (P ≤ 0.001), and reduced micturition volume by 60% (P ≤ 0.001). These changes were accompanied by an increased number of nonmicturition contractions from 3.7 ± 0.7 to 15 ± 2.7 (N = 6 in both groups, P ≤ 0.001 vs. control). Desensitization of intracolonic TRPV1 receptors before the induction of acute colitis restored the response of isolated detrusor strips to CCh but not to EFS stimulation. Cystometric parameters were significantly improved in animals with double treatment and approximated the control values. Our data suggest that acute colonic inflammation triggers the occurrence of detrusor instability via activation of TRPV1-related pathways. Comparison of the results obtained under in vitro vs. in vivo conditions provides evidence that intact neural pathways are critical for the development of an overactive bladder resulting from pelvic organ cross talk.

Topics: Acute Disease; Animals; Carbachol; Cholinergic Agents; Colitis; Diterpenes; Electric Stimulation; Male; Models, Animal; Muscle Contraction; Pelvic Pain; Rats; Rats, Sprague-Dawley; Signal Transduction; Trinitrobenzenesulfonic Acid; TRPV Cation Channels; Urinary Bladder; Urinary Bladder, Overactive

To investigate the efficacy and safety of a combination treatment with α(1)-blockers and antimuscarinics for detrusor overactivity in rats.. Rats with detrusor overactivity caused by a cerebral infarction were divided into four groups that received an i.v. administration of tamsulosin (0.1-1000 µg/kg); solifenacin (0.01-0.3 mg/kg); combined low doses of tamsulosin (0.008, 0.1 µg/kg) and solifenacin (0.01 mg/kg); or solifenacin (0.1, 0.3, 1.0 mg/kg) at 1-h intervals during the continuous administration of tamsulosin (0.01 µg/kg/h).. Both tamsulosin alone and solifenacin alone significantly increased bladder capacity in cerebral infarcted rats, but these effects were reduced in rats pretreated with resiniferatoxin. The combined low dose of tamsulosin and solifenacin resulted in a significant increase in bladder capacity compared to mono-administration of 0.01 mg/kg solifenacin (68.8 vs 19.8% of control value, respectively). In the group receiving solifenacin at 1-h intervals, solifenacin dose-dependently decreased bladder contraction duration and a significant reduction in bladder contraction pressure (by 35.0% of control value) was found at the highest dose (1.0 mg/kg). However, no reduction in bladder contraction duration was found even at the highest dose of solifenacin when co-administered with tamsulosin.. α(1)-Blockers and antimuscarinic agents have an additive ameliorative effect on detrusor overactivity when co-administered at low doses. α(1)-Blockers prevent the reduction in bladder contraction duration induced by a high-dose administration of antimuscarinic agents.

Topics: Adrenergic alpha-1 Receptor Antagonists; Analysis of Variance; Animals; Disease Models, Animal; Diterpenes; Drug Therapy, Combination; Female; Infarction, Middle Cerebral Artery; Muscarinic Antagonists; Muscle Contraction; Organ Size; Quinuclidines; Rats; Rats, Sprague-Dawley; Solifenacin Succinate; Statistics, Nonparametric; Sulfonamides; Tamsulosin; Tetrahydroisoquinolines; Urinary Bladder; Urinary Bladder, Overactive

Topics: Anti-Dyskinesia Agents; Antidepressive Agents; Behavior Control; Botulinum Toxins; Capsaicin; Cholinergic Antagonists; Diterpenes; Flavoxate; Humans; Parasympatholytics; Physical Therapy Modalities; Sensory System Agents; Urinary Bladder, Overactive

Recently, it has been demonstrated that intrathecal delivery of resiniferatoxin (RTX) produces strong analgesia, even in models of bone cancer pain. RTX has been investigated to treat bladder dysfunction of spinal origin, applied by intravesical instillation. However, RTX delivered by this route was not completely satisfactory in controlling urinary incontinence and high intravesical pressure. Thus, the present study assessed the effects of intrathecal injections of RTX in bladder dysfunction in rats with spinal cord transection (SCT). Bladder function was evaluated in SCT rats 24 h following intrathecal administration of RTX. Detrusor overactivity and intravesical pressure were reduced in a dose-dependent manner. This was accompanied by a decrease in spinal cord TRPV1 and CGRP, but not in IB4 binding sensory fibres. Also, intrathecal RTX induced a dose-dependent reduction in spinal cord activation of the ERK pathway. Overall, our results show that intrathecal administration of RTX effectively reduces detrusor overactivity and reduces intravesical pressure in models of complete chronic spinal cord transection by suppressing the activity of TRPV1 expressing afferent fibres. Also, intrathecal RTX decreases sensory input, as shown by reduced spinal ERK activation. These findings might be relevant for the management of patients with spinal cord injuries.

Topics: Animals; Calcitonin Gene-Related Peptide; Diterpenes; Extracellular Signal-Regulated MAP Kinases; Female; Injections, Spinal; Lectins; Neurotoxins; Rats; Rats, Wistar; Reflex; Ribosome Inactivating Proteins, Type 1; Saporins; Spinal Cord; Spinal Cord Injuries; TRPV Cation Channels; Urinary Bladder; Urinary Bladder, Overactive; Urination

We determined if cold environmental stress induced detrusor overactivity in conscious rats. We then examined the role of resiniferatoxin (RTX)-sensitive nerves in this response.. Three days prior to cystometric investigation, the urinary bladders of 12 female rats were cannulated. Six of the rats were treated with RTX 24 hr prior to cystometric investigation. The rats were exposed to three ambient temperature conditions: room temperature (RT, 27 degrees C) for 20 min, low temperature (LT, 4 degrees C) for 40 min, and RT again for 20 min. During each exposure, cystometric patterns of the rats were recorded. Additionally, neuronal structures of urinary bladders were visualized by immunohistochemistry.. When the conscious rats were suddenly transferred from RT to LT, the cooled rats exhibited micturition patterns of detrusor overactivity. After 20 min at LT, the response slowly improved. After returning to RT, the overactive detrusor response disappeared, reverting to patterns similar to those before transfer to LT. When the RTX-treated rats were exposed with cold stress, they also exhibited detrusor overactivity. However, it was significantly mitigated compared to the non-RTX-treated normal rats. The normal rats had distinct neuronal structures labeled with S100 and calcitonin gene-related peptide antibodies in the urinary bladders, but the RTX-treated rats had few.. Detrusor overactivity of the conscious rats was induced by cold environmental stress. A portion of the cold-stress detrusor overactivity might be mediated by RTX-sensitive neurological pathway. The cold-stress model would be useful to investigate lower urinary tract functions.

Topics: Animals; Behavior, Animal; Calcitonin Gene-Related Peptide; Cold Temperature; Consciousness; Diterpenes; Female; Immunohistochemistry; Neurons; Rats; Rats, Sprague-Dawley; S100 Proteins; Time Factors; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics

To investigate the correlation of transient receptor potential vanilloid subfamily 1 (TRPV1) mRNA expression levels and the clinical outcome of intravesical resiniferatoxin treatment in patients with idiopathic detrusor overactivity (IDO), as such treatment with vanilloids can be effective for DO.. In all, 28 patients with IDO refractory to anticholinergics were enrolled and treated with four weekly intravesical instillations of 10 nm resiniferatoxin. Eleven patients having ureteroscopic surgery served as controls. Two bladder wall biopsies were taken from the posterior wall by rigid cystoscopy. TRPV1 expression in the bladder wall samples was determined by individual quantitative reverse transcription-polymerase chain reaction, and immunohistochemical staining. Responders to the therapy were defined as those with an improvement in an urgency scale by >/=1, and with improved general satisfaction. Baseline TRPV1 expression was compared between responders, nonresponders and controls.. At 3 months, 14 patients (50%) were responders and in the other 14 the treatment failed (nonresponders). Bladder biopsies were available in seven responders and 11 nonresponders. Transcript levels before treatment correlated significantly with the therapeutic effect of resiniferatoxin (P = 0.004), with higher TRPV1 mRNA expression in responders (median 1.50, range 0.89-2.78) than nonresponders (0.74, 0.34-1.32). Responders also had higher TRPV1 expression levels than a control group (P = 0.067), but the TRPV1 transcript levels of nonresponders were not significantly different from those of the control (P = 0.367).. Successful intravesical resiniferatoxin treatment is closely associated with the over-expression of TRPV1 in the bladder mucosa and submucosa in patients with IDO.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Case-Control Studies; Diterpenes; Female; Humans; Immunohistochemistry; Male; Middle Aged; Muscarinic Antagonists; Muscle, Smooth; Prospective Studies; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Treatment Outcome; TRPV Cation Channels; Urinary Bladder, Overactive; Urodynamics

Intravesical resiniferatoxin (RTX) has been used with variable efficacy in the treatment of detrusor overactivity (DO). Patients with interstitial cystitis (IC) failed to benefit from this treatment, but a single placebo-controlled study in patients with non-IC painful bladders showed that RTX was effective in the short-term. We investigated the efficacy of intravesical RTX in patients with urgency and frequency due to increased bladder sensation.. Patients with intractable urgency and frequency, with or without urgency incontinence or bladder pain/discomfort, and with no urodynamic evidence of DO were recruited. After a single intravesical instillation of 100ml 50 nM RTX solution, patients were followed at 1, 3, and 6 mo for changes in urodynamics, bladder diary, the King's Health Questionnaire (KHQ), and degree of bladder pain.. Fifteen patients (mean age, 52.5 yr) were treated. RTX significantly improved maximum cystometric capacity, volume at first desire to void, mean micturition volume, 24-h frequency, and daytime frequency for up to 6 mo after treatment. The overall KHQ score improved at all time points, with sustained improvements in the Symptom Severity, Incontinence Impact, and Personal Relationships domains. A >50% decrease in pain was reported by five of seven patients with painful bladders at 1 mo, but only one of seven at 6 mo.. In our small open-label study, a single administration of intravesical RTX in patients with frequency and urgency due to increased bladder sensation significantly improved lower urinary tract symptoms, urodynamic parameters, and quality of life for up to 6 mo.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Diterpenes; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurotoxins; Quality of Life; Reflex, Abnormal; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics