Effects of Combination Treatment of Intravesical Resiniferatoxin Instillation and Hydrodistention in Patients with Refractory Painful Bladder Syndrome/Interstitial Cystitis: A Pilot Study

Ham, Byeong Kuk; Kim, Jae Heon; Oh, Mi Mi; Lee, Jeong Gu; Bae, Jae Hyun

doi:10.5213/inj.2012.16.1.41

Cited by 27 publications

(25 citation statements)

References 19 publications

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“…However, intravesical capsaicin and its ultrapotent analogue RTX failed to improve pain scores or symptoms in patients with severe pelvic pain or interstitial cystitis 124,142 . By contrast, hydrodistension combined with intravesical RTX significantly reduced pain at 1 month ( P = 0.022) and 3 months ( P = 0.041) follow-up duration in patients with IC/BPS 143 . Disappointing results with TRPV1 agonists have resulted in the pursuit of TRPV1 antagonists for clinical development.…”

Section: Targeting Receptors And/or Channelsmentioning

confidence: 94%

Receptors, channels, and signalling in the urothelial sensory system in the bladder

et al. 2016

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The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra, and urethral sphincters. At the level of the lumbosacral spinal cord, lower urinary tract reflex mechanisms are modulated by supraspinal controls with mechanosensory input from the urothelium, resulting in regulation of bladder contractile activity. The specific identity of the mechanical sensor is not yet known, but considerable interest exists in the contribution of transient receptor potential (TRP) channels to the mechanosensory functions of the urothelium. The sensory, transduction, and signalling properties of the urothelium can influence adjacent urinary bladder tissues including the suburothelial nerve plexus, interstitial cells of Cajal, and detrusor smooth muscle cells. Diverse stimuli, including those that activate TRP channels expressed by the urothelium, can influence urothelial release of chemical mediators (such as ATP). Changes to the urothelium are associated with a number of bladder pathologies that underlie urinary bladder dysfunction. Urothelial receptor and/or ion channel expression and the release of signalling molecules (such as ATP and nitric oxide) can be altered with bladder disease, neural injury, target organ inflammation, or psychogenic stress. Urothelial receptors and channels represent novel targets for potential therapies that are intended to modulate micturition function or bladder sensation.

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Section: Targeting Receptors And/or Channelsmentioning

confidence: 94%

Receptors, channels, and signalling in the urothelial sensory system in the bladder

et al. 2016

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“…For this reason, we need to focus on additional treatment modality for refractory IC/PBS which was defined as persistent, unacceptable symptoms despite PPS, hydrodistension, and TUC treatment [8]. …”

Section: Discussionmentioning

confidence: 99%

Pretreatment Features to Influence Effectiveness of Intravesical Hyaluronic Acid Instillation in Refractory Interstitial Cystitis/Painful Bladder Syndrome

et al. 2014

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PurposeTo determine the efficacy of intravesical hyaluronic acid (HA) instillation in treating patients with refractory interstitial cystitis/painful bladder syndrome (IC/PBS) and to identify any related factors that influence its therapeutic effect.MethodsThirty-three female IC/PBS patients who demonstrated poor or unsatisfactory responses to previous treatments between December 2010 and October 2012 were enrolled. Despite previous treatments, the enrolled patients had visual analogue scale (VAS) pain scores ≥4 and total scores (symptom and bother scores) ≥13 on the pelvic pain and urgency/frequency (PUF) questionnaire and ≥12 on the O'Leary-Sant interstitial cystitis symptoms index (ICSI)/problems index (ICPI). All patients received once weekly intravesical instillations of 40-mg HA diluted in 50-mL saline for 4 weeks. The efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to 4 weeks after treatment. Improvement was defined as a ≥2 decrease in the VAS. Moreover, we investigated the effects of the presence of Hunner's ulcer and previous treatment modalities on the therapeutic outcome of HA instillation.ResultsThe mean age was 57.0±1.8 years (range, 28-75 years). The VAS score significantly decreased from baseline to 4 weeks after treatment (-2.5, P<0.001). The mean changes in the PUF, ICSI, and ICPI from baseline to 4 weeks after the treatment were -3.8 (P<0.001), -2.3 (P<0.001), and -2.7 (P<0.001), respectively. Twenty patients (61%) showed improvements. Previous treatment modalities did not affect the efficacy of HA instillation and the presence of Hunner's ulcer was unrelated to outcomes. No complications were observed.ConclusionsThese results show that intravesical HA instillation is an effective and safe treatment for patients with refractory IC/PBS. Previous treatment modalities and presence of Hunner's ulcer do not affect the efficacy of HA instillation.

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“…Son efficacité en traitement local dans les études précliniques (injections sous-cutanée, intraganglionnaire et intrathécale) permet d'envisager des essais cliniques. Deux études pilotes sont en cours : l'injection intrathécale de RTX dans la prise en charge des douleurs cancéreuses en soins palliatifs [36] et l'injection intravésicale dans le traitement du syndrome de la vessie douloureuse et de la cystite [37]. …”

Section: La Résinifératoxine (Rtx)unclassified

TRPV1 dans les neuropathies douloureuses

Danigo¹,

Magy²,

Demiot³

2013

Med Sci (Paris)

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Ce récepteur est exprimé par les neurones sensitifs des ganglions rachidiens dorsaux et trigéminaux qui sécrètent du CGRP (calcitonin gene-related peptide) et de la substance P, deux neuropeptides. Des afférences sensitives positives pour TRPV1 ont été identifiées dans la vessie, le tractus gastro-intestinal et la peau [3]. L'état du canal est modulé par deux types de molécules : les agents qui favorisent son ouverture du canal, dits activateurs, et les agents qui induisent sa fermeture ou empêchent son ouverture, dits inhibiteurs.Agents activateurs TRPV1 est stimulé par des facteurs agissant directement sur le canal, tels qu'une température ressentie comme douloureuse (> 43 °C), un milieu extracellulaire acide, ou la fixation de vanilloïdes comme la capsaïcine, composé extrait du piment, ou la résinifératoxine (RTX), isolée à partir du latex de Euphorbia resinifera. Des molécules endogènes activatrices de TRPV1 ont aussi été identifiées : les endovanilloïdes qui regroupent les produits de la 12-lipoxygénase et l'anandamide [4]. TRPV1 peut être activé de façon indirecte par des facteurs de croissance, certains lipides et de nombreuses molécules de l'inflammation [5]. L'activation indirecte de TRPV1 aboutit à l'augmentation de la probabilité d'ouverture du canal, soit par la diminution du seuil d'activation à la chaleur, soit par la levée de l'inhibition de PIP 2 (phosphatidylinositol 4,5-biphosphate). La diminution du seuil d'activation à la chaleur implique des phénomènes de phosphorylation par la PKA et la PKC.

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Effects of Combination Treatment of Intravesical Resiniferatoxin Instillation and Hydrodistention in Patients with Refractory Painful Bladder Syndrome/Interstitial Cystitis: A Pilot Study

Cited by 27 publications

References 19 publications

Receptors, channels, and signalling in the urothelial sensory system in the bladder

Receptors, channels, and signalling in the urothelial sensory system in the bladder

Pretreatment Features to Influence Effectiveness of Intravesical Hyaluronic Acid Instillation in Refractory Interstitial Cystitis/Painful Bladder Syndrome

TRPV1 dans les neuropathies douloureuses

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