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• W2000807287 abstract "No AccessJournal of UrologyAdult Urology: Voiding Dysfunction1 Sep 2005DECREASED SENSORY RECEPTORS P2X3 AND TRPV1 IN SUBUROTHELIAL NERVE FIBERS FOLLOWING INTRADETRUSOR INJECTIONS OF BOTULINUM TOXIN FOR HUMAN DETRUSOR OVERACTIVITY A. APOSTOLIDIS, R. POPAT, Y. YIANGOU, D. COCKAYNE, A.P.D.W. FORD, J.B. DAVIS, P. DASGUPTA, C.J. FOWLER, and P. ANAND A. APOSTOLIDISA. APOSTOLIDIS More articles by this author , R. POPATR. POPAT More articles by this author , Y. YIANGOUY. YIANGOU More articles by this author , D. COCKAYNED. COCKAYNE More articles by this author , A.P.D.W. FORDA.P.D.W. FORD More articles by this author , J.B. DAVISJ.B. DAVIS More articles by this author , P. DASGUPTAP. DASGUPTA More articles by this author , C.J. FOWLERC.J. FOWLER More articles by this author , and P. ANANDP. ANAND More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000169481.42259.54AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT/A may affect sensory fibers. We investigated a possible effect of BoNT/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or idiopathic DO. Materials and Methods: A total of 38 patients (22 with neurogenic DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and voiding diary were also recorded. Specimens were studied immunohistochemically for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls. Results: P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test p=0.0004 and p=0.0008, respectively), when significant improvements were observed in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4 weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR suburothelial fibers remained unchanged after treatment at both followups (p=0.85 and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR also appeared unchanged. Conclusions: Decreased levels of sensory receptors P2X3 and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity. References 1 : Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol2000; 164: 692. Link, Google Scholar 2 : Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci USA1999; 96: 3200. Google Scholar 3 : Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity following intravesical resiniferatoxin treatment. BJU Int2004; 93: 770. Google Scholar 4 : P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur Urol2004; 46: 247. 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Link, Google Scholar From the Peripheral Neuropathy Unit, Hammersmith Hospital, Imperial College London (AA, YY, PA), Department of Uro-Neurology, National Hospital for Neurology and Neurosurgery, University College London Hospital (AA, RP, PD, CJF), and Department of Urology, Guy’s and St. Thomas’ Hospitals (PD), London, the Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow (JBD), United Kingdom, and the Neurobiology Unit, Roche Palo Alto, Palo Alto, California (DC, APDWF)© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byNitti V, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X and Haag-Molkenteller C (2016) OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled TrialJournal of Urology, VOL. 197, NO. 2S, (S216-S223), Online publication date: 1-Feb-2017.Wein A (2018) Re: Reduction of Urgency Severity is the Most Important Factor in the Subjective Therapeutic Outcome of Intravesical OnabotulinumtoxinA Injection for Overactive BladderJournal of Urology, VOL. 198, NO. 4, (748-752), Online publication date: 1-Oct-2017.Nitti V, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X and Haag-Molkenteller C (2018) OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled TrialJournal of Urology, VOL. 189, NO. 6, (2186-2193), Online publication date: 1-Jun-2013.Takahashi R, Yunoki T, Naito S and Yoshimura N (2018) Differential Effects of Botulinum Neurotoxin A on Bladder Contractile Responses to Activation of Efferent Nerves, Smooth Muscles and Afferent Nerves in RatsJournal of Urology, VOL. 188, NO. 5, (1993-1999), Online publication date: 1-Nov-2012.Datta S, Roosen A, Pullen A, Popat R, Rosenbaum T, Elneil S, Dasgupta P, Fowler C and Apostolidis A (2018) Immunohistochemical Expression of Muscarinic Receptors in the Urothelium and Suburothelium of Neurogenic and Idiopathic Overactive Human Bladders, and Changes With Botulinum Neurotoxin AdministrationJournal of Urology, VOL. 184, NO. 6, (2578-2585), Online publication date: 1-Dec-2010.Roosen A, Apostolidis A, Elneil S, Khan S, Panicker J, Brandner S, Fowler C and Kessler T (2018) Cadherin-11 Up-Regulation in Overactive Bladder Suburothelial MyofibroblastsJournal of Urology, VOL. 182, NO. 1, (190-195), Online publication date: 1-Jul-2009.Charrua A, Reguenga C, Cordeiro J, Correiade-Sá P, Paule C, Nagy I, Cruz F and Avelino A (2018) Functional Transient Receptor Potential Vanilloid 1 is Expressed in Human Urothelial CellsJournal of Urology, VOL. 182, NO. 6, (2944-2950), Online publication date: 1-Dec-2009.Karsenty G, Elzayat E, Delapparent T, St-Denis B, Lemieux M and Corcos J (2018) Botulinum Toxin Type A Injections Into the Trigone to Treat Idiopathic Overactive Bladder do Not Induce Vesicoureteral RefluxJournal of Urology, VOL. 177, NO. 3, (1011-1014), Online publication date: 1-Mar-2007.Kuo H (2018) Comparison of Effectiveness of Detrusor, Suburothelial and Bladder Base Injections of Botulinum Toxin A for Idiopathic Detrusor OveractivityJournal of Urology, VOL. 178, NO. 4, (1359-1363), Online publication date: 1-Oct-2007.Altaweel W, Jednack R, Bilodeau C and Corcos J (2018) Repeated Intradetrusor Botulinum Toxin Type A in Children With Neurogenic Bladder Due to MyelomeningoceleJournal of Urology, VOL. 175, NO. 3, (1102-1105), Online publication date: 1-Mar-2006.Schmid D, Sauermann P, Werner M, Schuessler B, Blick N, Muentener M, Strebel R, Perucchini D, Scheiner D, Schaer G, John H, Reitz A, Hauri D and Schurch B (2018) Experience With 100 Cases Treated With Botulinum-A Toxin Injections in the Detrusor Muscle for Idiopathic Overactive Bladder Syndrome Refractory to AnticholinergicsJournal of Urology, VOL. 176, NO. 1, (177-185), Online publication date: 1-Jul-2006.Chuang Y and Chancellor M (2018) The Application of Botulinum Toxin in the ProstateJournal of Urology, VOL. 176, NO. 6, (2375-2382), Online publication date: 1-Dec-2006. Volume 174Issue 3September 2005Page: 977-983 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordsbotulinum toxins, urinary incontinencereflex, abnormalcapsaicin receptor, neurotransmittersMetricsAuthor Information A. APOSTOLIDIS More articles by this author R. POPAT More articles by this author Y. YIANGOU More articles by this author D. COCKAYNE More articles by this author A.P.D.W. FORD More articles by this author J.B. DAVIS More articles by this author P. DASGUPTA More articles by this author C.J. FOWLER More articles by this author P. ANAND More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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