INTRAVESICAL BOTULINUM TOXIN A ADMINISTRATION PRODUCES ANALGESIA AGAINST ACETIC ACID INDUCED BLADDER PAIN RESPONSES IN RATS

No AccessJournal of UrologyInvestigative Urology1 Oct 2004INTRAVESICAL BOTULINUM TOXIN A ADMINISTRATION PRODUCES ANALGESIA AGAINST ACETIC ACID INDUCED BLADDER PAIN RESPONSES IN RATS YAO-CHI CHUANG, NAOKI YOSHIMURA, CHAO-CHENG HUANG, PO-HUI CHIANG, and MICHAEL B. CHANCELLOR YAO-CHI CHUANGYAO-CHI CHUANG , NAOKI YOSHIMURANAOKI YOSHIMURA , CHAO-CHENG HUANGCHAO-CHENG HUANG , PO-HUI CHIANGPO-HUI CHIANG , and MICHAEL B. CHANCELLORMICHAEL B. CHANCELLOR View All Author Informationhttps://doi.org/10.1097/01.ju.0000137844.77524.97AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: There is evidence that botulinum toxin A (BTX-A) might have analgesic properties. However, the mechanisms by which BTX-A alters pain remain largely unexplored. In the bladder afferent nerve fibers contain calcitonin gene-related peptide (CGRP). In this study we investigated the effect of intravesical BTX-A administration on CGRP immunoreactivity and bladder hyperactivity in an acetic acid induced bladder pain model in rats. Materials and Methods: Experimental and control animals were catheterized and intravesically exposed to protamine sulfate (1 ml, 10 mg/ml), followed by BTX-A (1 ml, 25 U/ml) or saline, respectively. Three or 7 days after intravesical therapy continuous cystometrograms were performed using urethane anesthesia by filling the bladder (0.08 ml per minute) with saline, followed by 0.3% acetic acid. Bladder immunohistochemistry was used to detect CGRP. Results: The intercontraction interval (ICI) was decreased after acetic acid instillation (50.2% and 65.0%) in the control group at days 3 and 7, respectively. However, rats that received BTX-A showed a significantly decreased response (28.6% ICI decrease) to acetic acid instillation at day 7. This effect was not observed at day 3 (62.2% ICI decrease). Increased CGRP immunoreactivity was detected in the BTX treated group at day 7, which was not detected at day 3. Conclusions: Intravesical BTX administration blocked acetic acid induced bladder pain responses and inhibited CGRP release from afferent nerve terminals. These results support the clinical application of BTX-A for the treatment of interstitial cystitis and other types of visceral pain. References 1 : Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). J Urol1991; 145: 732. Link, Google Scholar 2 : Treatment of interstitial cystitis with intravesical heparin. Br J Urol1994; 73: 504. Google Scholar 3 : The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor. J Urol2001; 165: 975. Link, Google Scholar 4 : Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis. J Urol1992; 147: 587. 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Link, Google Scholar From the Departments of Urology (Y-CC, P-HC) and Pathology (C-CH), Chang Gung Memorial Hospital, Kaohsiung, Taiwan, and Department of Urology, University of Pittsburgh School of Medicine (NY, MBC), Pittsburgh, Pennsylvania© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byChuang Y, Huang T, Tyagi P and Huang C (2015) Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Low Energy Shock WavesJournal of Urology, VOL. 196, NO. 2, (599-608), Online publication date: 1-Aug-2016.Chuang Y, Kaufmann J, Chancellor D, Chancellor M and Kuo H (2014) Bladder Instillation of Liposome Encapsulated OnabotulinumtoxinA Improves Overactive Bladder Symptoms: A Prospective, Multicenter, Double-Blind, Randomized TrialJournal of Urology, VOL. 192, NO. 6, (1743-1749), Online publication date: 1-Dec-2014.Pinto R, Lopes T, Silva J, Silva C, Dinis P and Cruz F (2012) Persistent Therapeutic Effect of Repeated Injections of Onabotulinum Toxin A in Refractory Bladder Pain Syndrome/Interstitial CystitisJournal of Urology, VOL. 189, NO. 2, (548-553), Online publication date: 1-Feb-2013.Chuang Y, Tyagi P, Huang C, Yoshimura N, Wu M, Kaufman J and Chancellor M (2009) Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using LiposomesJournal of Urology, VOL. 182, NO. 2, (786-792), Online publication date: 1-Aug-2009.Chuang Y, Yoshimura N, Huang C, Wu M, Chiang P and Chancellor M (2008) Intraprostatic Botulinum Toxin A Injection Inhibits Cyclooxygenase-2 Expression and Suppresses Prostatic Pain on Capsaicin Induced Prostatitis Model in RatJournal of Urology, VOL. 180, NO. 2, (742-748), Online publication date: 1-Aug-2008.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.Rapp D, Turk K, Bales G and Cook S (2018) Botulinum Toxin Type A Inhibits Calcitonin Gene-Related Peptide Release From Isolated Rat BladderJournal of Urology, VOL. 175, NO. 3, (1138-1142), Online publication date: 1-Mar-2006.Chuang Y, Huang C, Kang H, Chiang P, Demiguel F, Yoshimura N and Chancellor M (2018) Novel Action of Botulinum Toxin on the Stromal and Epithelial Components of the Prostate GlandJournal of Urology, VOL. 175, NO. 3, (1158-1163), Online publication date: 1-Mar-2006.Chancellor M (2018) URGENCY, BOTULINUM TOXIN AND HOW BOTULINUM TOXIN CAN HELP URGENCYJournal of Urology, VOL. 174, NO. 3, (818-818), Online publication date: 1-Sep-2005.APOSTOLIDIS A, POPAT R, YIANGOU Y, COCKAYNE D, FORD A, DAVIS J, DASGUPTA P, FOWLER C and ANAND P (2018) DECREASED SENSORY RECEPTORS P2X3 AND TRPV1 IN SUBUROTHELIAL NERVE FIBERS FOLLOWING INTRADETRUSOR INJECTIONS OF BOTULINUM TOXIN FOR HUMAN DETRUSOR OVERACTIVITYJournal of Urology, VOL. 174, NO. 3, (977-983), Online publication date: 1-Sep-2005. Volume 172Issue 4 Part 1October 2004Page: 1529-1532 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsbladderpainurodynamicscystitisinterstitialbotulinum toxin type AMetrics Author Information YAO-CHI CHUANG Financial interest and/or other relationship with Allergan. More articles by this author NAOKI YOSHIMURA More articles by this author CHAO-CHENG HUANG More articles by this author PO-HUI CHIANG More articles by this author MICHAEL B. CHANCELLOR Financial interest and/or other relationship with OrthoMcNeil, Pfizer, Lilly, Watson, Cook and Yamanouchi. More articles by this author Expand All Advertisement PDF downloadLoading ...