resiniferatoxin and Cystitis--Interstitial

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Topics: Administration, Intravesical; Botulinum Toxins, Type A; Brazil; Chondroitin Sulfates; Clinical Decision-Making; Cystitis, Interstitial; Dimethyl Sulfoxide; Diterpenes; Humans; Hyaluronic Acid; Lidocaine; Mycobacterium bovis; Pentosan Sulfuric Polyester; Treatment Outcome

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

Interstitial cystitis/painful bladder syndrome is a chronic condition that causes debilitating bladder pain which can be associated with urgency, frequency and nocturia. Its cause is not clear and it is still a disease diagnosed by exclusion. Oral or intravesical therapies are the main stay of treatment whilst surgical procedures are reserved for refractory cases. This condition usually warrants a multidisciplinary approach for optimum outcome. This article gives an overview of the changes in definition, aetiopathogenesis and available treatments.

Topics: Administration, Intravesical; Analgesics; Antidepressive Agents, Tricyclic; Botulinum Toxins; Cystitis, Interstitial; Dimethyl Sulfoxide; Diterpenes; Female; Heparin; Humans; Male; Pentosan Sulfuric Polyester

The objective of the study was to assess the effectiveness of intravesical treatment for painful bladder syndrome (PBS).. A systematic review was performed until December 31, 2010. The selection criteria included only randomized controlled trials of PBS patients who received intravesical treatment. The primary outcomes measures were clinical and urodynamic parameters. Relative risk and mean differences were used for binary and continuous outcomes respectively, with confidence interval of 95%.. The search strategy identified 770; however, only 28 eligible trials met methodological requirements for complete analysis. Altogether, the review included four treatment modalities: resiniferatoxin, Bacillus Calmette-Guérin (BCG), oxybutynin, and alkalinized lidocaine. Meta-analysis of BCG therapy showed improvement in symptoms according to the Wisconsin Interstitial Cystitis Symptom Inventory, but no difference in 24-h urinary frequency.. Meta-analysis showed an improvement exclusively of the symptoms as measured by the Wisconsin Interstitial Cystitis Inventory, but not in 24-h urinary frequency, with BCG therapy. Further randomized clinical trials, including trials of more recent drugs, are required for evaluation of intravesical therapies for PBS.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Anesthetics, Local; BCG Vaccine; Cystitis, Interstitial; Diterpenes; Humans; Lidocaine; Mandelic Acids; Muscarinic Antagonists; Neurotoxins

Resiniferatoxin, a treatment based on a physiopathological concept (the involvement of C fibers and transient receptor potential vanilloid 1 in the transmission of pain) is undergoing evaluation for interstitial cystitis. We evaluated the current evidence from relevant studies identified in PubMed and Scopus databases. Six studies provided contradictory results regarding the effectiveness of resiniferatoxin treatment. The largest study showed no improvement of overall symptoms following a single administration of resiniferatoxin. Three other articles that studied the effectiveness of a single dose of resiniferatoxin gave contradictory results. However, the other two studies, those that examined the effect of multiple or prolonged administration schemes, gave more encouraging results. The use of the regimen is generally well tolerated although mild adverse events such as increase of bladder pain during instillation were sometimes reported by patients and serious adverse events rarely occur. In conclusion, the effectiveness of resiniferatoxin in the treatment of interstitial cystitis remains unknown.

Topics: Cystitis, Interstitial; Diterpenes; Humans; Neurotoxins; Pain Measurement; Treatment Outcome

Painful Bladder Syndrome/Interstitial Cystitis (PBS/IC) occurs predominantly in women. It is a poorly-understood condition with symptoms of bladder pain, urinary frequency, urgency and nocturia. Treatments for PBS/IC include dietary/lifestyle interventions, oral medication, intravesical instillations and, in some cases, surgery. Success rates are generally modest and there is little consensus as to the best form of treatment for this condition.. To assess the effectiveness of intravesical treatment for PBS/IC.. We searched the Cochrane Incontinence Group specialised trials register (30 May 2006) as well as reference lists of all selected trials. Recognised researchers in the field were contacted for any additional relevant material.. Randomised or quasi-randomised controlled trials were included in the review if they had recruited participants with a clinical diagnosis of PBS/IC and if at least one arm of the trial was treatment with an intravesical preparation. Outcome measures were pre-determined, the primary ones being the effect on pain and bladder capacity. Others included symptomatic response to treatment, quality-of-life assessment, economic factors and adverse events.. Two reviewers independently assessed trial eligibility and quality, then extracted relevant data from the studies.. Nine eligible trials were identified - six parallel group, one incomplete cross-over and two cross-over trials - with a total of 616 participants. Six trials compared an 'active' instillation with placebo instillation, two compared different types of instillation, and one was a comparison of an instillation plus bladder training versus bladder training alone. Altogether, the review included trials of six different types of intravesical instillation: Resiniferatoxin, Dimethyl sulfoxide, BCG, pentosanpolysulphate, oxybutin, and alkalinisation of urine pH. Confidence intervals were generally wide. Resiniferatoxin was not associated with sustained differences in the review outcomes reported but pain during instillation and withdrawal from treatment was significantly more common. The data available about Dimethyl sulfoxide (DMSO) were very limited but with no apparent differences from placebo. Groups treated with BCG tended to report less pain and fewer general symptoms. Although adverse events were commonly reported, these were no more common after BCG than after placebo instillation. The few data about Pentosanpolysulphate tended to favour the actively treated, but with wide confidence intervals; there was little information about adverse events. Oxybutinin instillation was associated with increased bladder capacity, reduced frequency, improved quality of life scores and fewer drop-outs. Alkalinisation of urine pH did not make any clear difference, but with potentially wide confidence intervals.. Overall, the evidence base for treating PBS/IC using intravesical preparations is limited and the potential for meta-analysis reduced by variation in the outcome measures used. The quality of trial reports was mixed and in some cases this precluded any meaningful data extraction. BCG and oxybutin are reasonably well-tolerated and evidence is most promising for these. Resiniferatoxin showed no evidence of effect for most outcomes and caused pain, which reduced treatment compliance. There is little evidence for the other treatments included in this review. Randomised controlled trials are still needed and study design should incorporate outcomes that are most relevant to these with PBS/IC and should be standardised.

Topics: Administration, Intravesical; BCG Vaccine; Cystitis, Interstitial; Dimethyl Sulfoxide; Diterpenes; Humans; Mycobacterium bovis; Pain Management; Pentosan Sulfuric Polyester; Randomized Controlled Trials as Topic

Recent years have brought dramatic advances in the clinician's ability to offer effective pharmacotherapy to patients who have interstitial cystitis. Medical treatments have been developed and applied to reduce the interstitial cystitis symptoms of pelvic pain and urinary urgency/frequency, and to address underlying causes of the disorder. In addition, advances in the understanding of the natural history of interstitial cystitis have revealed that it is insidiously progressive and the classical definition--rare, severe and difficult to treat--is in fact the relatively uncommon, advanced stage of a disorder that affects most individuals in a mild-to-moderate and readily treatable form. This recognition has led to the identification of large numbers of previously unsuspected cases of interstitial cystitis, and the successful treatment of many individuals in the early stages of interstitial cystitis when it is far more responsive to therapy. A heparinoid-based multimodal medical regimen can effectively control symptoms and address disease pathophysiology in the majority of cases. Intravesical therapeutic solutions are new and promising adjunctive therapies that can offer immediate symptom relief during symptom flares, and for patients who are just beginning medical therapy.

Topics: Administration, Intravesical; Analgesics, Non-Narcotic; Anesthetics, Local; Anti-Inflammatory Agents; Clinical Trials as Topic; Cystitis, Interstitial; Dimethyl Sulfoxide; Diterpenes; Drug Administration Schedule; Drug Therapy, Combination; Heparinoids; Humans; Lidocaine; Neurotoxins; Pelvic Pain; Pentosan Sulfuric Polyester; Sodium Bicarbonate

Topics: Administration, Intravesical; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Botulinum Toxins; Capsaicin; Cholinergic Antagonists; Cresols; Cystitis, Interstitial; Diterpenes; Humans; Mandelic Acids; Neurotoxins; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Diseases; Urination Disorders

Current medications used in the treatment of interstitial cystitis (IC) have limited efficacy. This prospective study investigated the efficacy of multiple intravesical instillations of resiniferatoxin (RTX) at the concentration of 10 nM.. Patients with proven IC previously treated with traditional medications for more than 6 months without clinical benefit were enrolled. They were excluded if bladder outlet obstruction or urinary tract infection was present. Intravesical instillation of low-dose RTX (10 nM) once weekly for 4 weeks was performed at the outpatient department. International Prostate Symptom Score (IPSS), 5-Point Pain Scale, and Quality of Life Index (QOL Index) were recorded. A videourodynamic study was done at baseline and 3 months after treatment.. The therapeutic results and urodynamic parameters were compared between baseline and 3 months. Thirteen patients, including 10 women and 3 men, were enrolled in this study. The mean duration of IC symptoms was 4.4 +/- 2.5 years. The mean duration of active treatment was 15.3 +/- 8.6 months. One female patient dropped out due to severe bladder pain after RTX instillation. Among the 12 patients who completed the study treatment, subjective assessment revealed that 2 had an excellent therapeutic result, 5 had an improved result and 5 remained unchanged from baseline. The overall satisfactory rate was 58.3%. IPSS, 5-Point Pain Scale, and QOL Index were significantly decreased after RTX treatment. There was no significant increase in mean functional bladder capacity or change in urodynamic parameters. No serious adverse event occurred after RTX treatment.. This study suggests that multiple intravesical instillations of RTX at the concentration of 10 nM are effective in relieving lower urinary tract symptoms in patients with refractory IC. The treatment is tolerable and suitable for use on an outpatient clinic basis.

Topics: Administration, Intravesical; Cystitis, Interstitial; Cystoscopy; Diterpenes; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurotoxins; Prospective Studies; Quality of Life; Treatment Outcome; Urodynamics; Video Recording

Interstitial cystitis is a painful bladder condition of unknown etiology and poorly understood pathophysiology. Current therapies have met with limited success. Vanilloid receptor agonists such as resiniferatoxin (RTX) desensitize C-fibers that transmit pain; it is hypothesized that such drugs will be effective in the treatment of interstitial cystitis and painful bladder syndrome by decreasing the pain that leads to urinary frequency and urgency.. A randomized, double-blind, placebo controlled study was conducted in 163 patients with interstitial cystitis. Participants were randomly assigned to receive a single intravesical dose of 50 ml of either RTX 0.01 microM, 0.05 microM, 0.10 microM, or placebo. Safety and efficacy was evaluated over 12 weeks. The primary efficacy endpoint was the Global Response Assessment, a 7-point scale rating overall change in symptoms of interstitial cystitis after 4 weeks. Secondary efficacy endpoints included reduction in pain, urgency, frequency, nocturia, average void volume, and the O'Leary-Sant Symptom and Problem Indexes.. RTX did not improve overall symptoms, pain, urgency, frequency, nocturia, or average void volume during 12 weeks followup. RTX resulted in a dose-dependent increase in the incidence of instillation pain, but was otherwise generally well tolerated.. In the largest prospective, randomized clinical trial reported to date with intravesical vanilloid therapy, single administration of RTX at doses of 0.01 microM to 0.10 microM was not effective in patients with interstitial cystitis.

Topics: Administration, Intravesical; Adult; Aged; Cystitis, Interstitial; Diterpenes; Double-Blind Method; Female; Humans; Male; Middle Aged; Neurotoxins

Increased afferent excitability has been proposed as an important pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB). In this study, we investigated whether herpes simplex virus (HSV) vectors encoding poreless TRPV1, in which the segment in C terminus of TRPV1 receptor is deleted, suppress bladder overactivity and pain behavior using a rat model of chemical cystitis. Replication-defective HSV vectors encoding poreless TRPV1 were injected into the bladder wall of adult female Sprague-Dawley rats. Additionally, recombinant HSV virus (vHG) vectors were injected as control. Cystometry (CMG) under urethane anesthesia was performed 1 week after viral injection to evaluate bladder overactivity induced by resiniferatoxin (RTx, a TRPV1 agonist). RTx-induced nociceptive behavior such as licking (lower abdominal licking) and freezing (motionless head-turning) was observed 2 weeks after viral injection. GFP expression in L4/L6/S1 dorsal root ganglia and the bladder as well as c-Fos-positive cells in the L6 spinal cord dorsal horn were also evaluated 2 weeks after viral injection. In CMG, the poreless TRPV1 vector-treated group showed a significantly smaller reduction in intercontraction intervals and voided volume after RTx infusion than the vHG-treated control group. The number of the RTx-induced freezing events was significantly decreased in the poreless TRPV1 group than in the vHG group, whereas there was no significant difference of the number of RTx-induced licking events between groups. The number of c-Fos-positive cells in the DCM and SPN regions of the L6 spinal dorsal horn was significantly smaller in the poreless TRPV1 group than in the vHG group. Our results indicated that HSV vector-mediated gene delivery of poreless TRPV1 had a therapeutic effect on TRPV1-mediated bladder overactivity and pain behavior. Thus, the HSV vector-mediated gene therapy targeting TRPV1 receptors could be a novel modality for the treatment of OAB and/or hypersensitive bladder disorders such as IC/BPS.

Topics: Animals; Cystitis, Interstitial; Diterpenes; Female; Genetic Therapy; Genetic Vectors; Nociception; Rats; Rats, Sprague-Dawley; Simplexvirus; TRPV Cation Channels

Although hydrodistention of the bladder is accepted as the initial treatment for patients with interstitial cystitis (IC), second-line treatment for worsening symptoms is not concretely established. Resiniferatoxin (RTX) desensitizes bladder afferent c-fibers and its intravesical instillation is effective for patients with detrusor overactivity. We studied the clinical relevance of intravesical treatment with RTX for patients with IC. The treatment was performed for 3 patients with incomplete improvement after hydrodistention. All 3 patients were free of bladder pain posttreatment and had slight improvement of the maximum voided volume. Though RTX treatment requires general anesthesia against severe bladder pain it is effective for selected patients with interstitial cystitis and can be potentially used as one of the treatment options.

Topics: Administration, Intravesical; Aged; Cystitis, Interstitial; Diterpenes; Female; Humans

The management of patient with interstitial cystitis (IC) remains a challenge because no single agent has proven effective. IC is a chronic sterile inflammatory disease of the bladder of unknown etiology characterized by urinary frequency, urgenecy, nocturia and lower abdominal pain. We experienced anesthetic management of five patients with IC during intravesical resiniferatoxin (RTX) therapy. RTX is associated with irritative urinary symptom during bladder instillation. The patients with IC had bladder instillation with 100 ml of 10(-8) M RTX solution for 30 min. The first patient received combined spinal-epidural anesthesia (CSEA), and the others general anesthesia. The patient with regional anesthesia had no critical troubles related to circulatory status during the procedure, but increases of blood pressure after instillation of RTX were observed in two patients receiving general anesthesia. In spite of the increase in blood pressure during general anesthesia, regional anesthesia should not be used, because the effect of RTX on the spinal cord has to be maintained.

Topics: Administration, Intravesical; Aged; Anesthesia, Epidural; Anesthesia, General; Anesthesia, Spinal; Cystitis, Interstitial; Diterpenes; Female; Humans; Male; Middle Aged

Topics: Afferent Pathways; Animals; Arousal; Cats; Cerebral Cortex; Cystitis, Interstitial; Diterpenes; Efferent Pathways; Heart Rate; Neurotoxins; Pain; Reflex; Respiration; Tail; Urinary Bladder