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      Therapeutic Effect of Botulinum Toxin A on Sensory Bladder Disorders—From Bench to Bedside

      review-article
      1 , 2 , 3 , 1 , 2 , *
      Toxins
      MDPI
      bladder, sensation, therapy, pathophysiology

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          Abstract

          Bladder oversensitivity arises from several different conditions involving the bladder, bladder outlet, systemic or central nervous system diseases. Increase of the bladder sensation results from activation of the sensory receptors in the urothelial cells or suburothelial tissues. Medical treatment targeting the overactive bladder (OAB) or interstitial cystitis (IC) might relieve oversensitive bladder symptoms (frequency, urgency and pain) in a portion of patients, but a certain percentage of patients still need active management. Botulinum toxin A (BoNT-A) has been demonstrated to have anti-inflammatory and antinociceptive effects in bladder sensory disorders and has been shown effective in the reduction of bladder oversensitivity and the increase of functional bladder capacity. For patients with OAB, urgency and urinary incontinence improved, while in patients with IC, bladder pain could be relieved in association with reduction of bladder oversensitivity after BoNT-A intravesical injection. Histological evidence has confirmed the therapeutic mechanism and clinical efficacy of intravesical BoNT-A injection on patients with OAB or IC. Bladder oversensitivity can also be relieved with the instillation of liposome encapsulated BoNT-A or low energy show waves (LESWs), which enable the BoNT-A molecule to penetrate into the urothelium and suburothelial space without affecting the detrusor contractility. Liposome encapsulated BoNT-A or combined LESWs and BoNT-A instillation might be future treatment alternatives for bladder oversensitivity in sensory bladder disorders.

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          Most cited references116

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          Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.

          The purpose of this amendment is to provide an updated clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome based upon data received since the publication of original guideline in 2011.
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            SV2 is the protein receptor for botulinum neurotoxin A.

            How the widely used botulinum neurotoxin A (BoNT/A) recognizes and enters neurons is poorly understood. We found that BoNT/A enters neurons by binding to the synaptic vesicle protein SV2 (isoforms A, B, and C). Fragments of SV2 that harbor the toxin interaction domain inhibited BoNT/A from binding to neurons. BoNT/A binding to SV2A and SV2B knockout hippocampal neurons was abolished and was restored by expressing SV2A, SV2B, or SV2C. Reduction of SV2 expression in PC12 and Neuro-2a cells also inhibited entry of BoNT/A, which could be restored by expressing SV2 isoforms. Finally, mice that lacked an SV2 isoform (SV2B) displayed reduced sensitivity to BoNT/A. Thus, SV2 acts as the protein receptor for BoNT/A.
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              Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019

              The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of non-neurogenic overactive bladder (OAB).
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                09 March 2020
                March 2020
                : 12
                : 3
                : 166
                Affiliations
                [1 ]Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; redeemer1019@ 123456yahoo.com.tw
                [2 ]Department of Urology, Buddhist Tzu Chi University, Hualien 970, Taiwan
                [3 ]Department of Nursing, Hualien Tzu Chi General Hospital, Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan; wanzu666@ 123456gmail.com
                Author notes
                [* ]Correspondence: hck@ 123456tzuchi.com.tw ; Tel.: +886-3-8561825 (ext. 2113); Fax: +886-3-8560794
                Article
                toxins-12-00166
                10.3390/toxins12030166
                7150911
                32182780
                7bd664a2-8418-4f17-a1d4-f860f4267d6e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 February 2020
                : 06 March 2020
                Categories
                Review

                Molecular medicine
                bladder,sensation,therapy,pathophysiology
                Molecular medicine
                bladder, sensation, therapy, pathophysiology

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