{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:52:06Z","timestamp":1785887526111,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T00:00:00Z","timestamp":1567123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxin A (BoNT\/A) appears to be one of the best intravesical treatments for interstitial cystitis\/bladder painful syndrome (IC\/BPS). We aimed to point out what the evidence is regarding the effects of BoNT\/A intravesically injected in patients with IC\/BPS. We performed a systematic review of all randomized controlled trials (RCTs) assessing BoNT\/A for IC\/BPS by using Medline, EMBASE, CINAHL, CENTRAL and MetaRegister of Controlled Trials. Standardized mean differences (SMD) were extracted from the available trials and combined in a meta-analysis applying a random effect model, including heterogeneity of effects. Twelve trials were identified. Significant benefits from BoNT\/A injections were detected in: Interstitial Cystitis Symptom Index and Problem Index (ICSI, ICPI) (small to medium effect size: SMD = \u20130.302; p = 0.007 and \u20130.430, p = 0.004, respectively); Visual Analog Scale (VAS) for pain and day-time urinary frequency (medium effect size: SMD = \u20130.576, p &lt; 0.0001 and \u20130.546, p = 0.013, respectively). A great effect size was detected for post-void residual volume (PVR, SMD = 0.728; p =0.002) although no clinically relevant in most cases. Great heterogeneity was observed in treatments\u2019 methodologies and symptoms assessment. Overall, BoNT\/A intravesical injections significantly improve some of the most relevant symptoms affecting IC\/BPS patients.<\/jats:p>","DOI":"10.3390\/toxins11090510","type":"journal-article","created":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T10:31:17Z","timestamp":1567161077000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Botulinum Neurotoxin A Intravesical Injections in Interstitial Cystitis\/Bladder Painful Syndrome: A Systematic Review with Meta-Analysis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6460-6587","authenticated-orcid":false,"given":"Antonella","family":"Giannantoni","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences and Neurosciences, Functional and Surgical Urology Unit, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3486-1226","authenticated-orcid":false,"given":"Marilena","family":"Gubbiotti","sequence":"additional","affiliation":[{"name":"Department of Urology, San Donato Hospital, 52100 Arezzo, Italy"},{"name":"Serafico Institute of Assisi, Research centre \u201cInVita\u201d, Assisi, 06081 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Bini","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/nau.23072","article-title":"A standard for terminology in chronic pelvic pain syndromes: Areport from the chronic pelvic pain working group of the international continence society","volume":"36","author":"Doggweiler","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.eururo.2007.09.019","article-title":"Diagnostic criteria, classification, and nomenclature for painful bladder syndrome\/interstitial cystitis: An ESSIC proposal","volume":"53","author":"Nordling","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/S0090-4295(00)00845-1","article-title":"Treatment used in women with interstitial cystitis: The interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group","volume":"56","author":"Rovner","year":"2000","journal-title":"Urology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41585-018-0135-5","article-title":"MAPP Research Network Study Group. Urologic chronic pelvic pain syndrome: Insights from the MAPP Research Network","volume":"16","author":"Clemens","year":"2019","journal-title":"Nat. Rev. Urol"},{"key":"ref_5","first-page":"141","article-title":"Chronic prostatitis\/chronic pelvic pain syndrome and interstitial cystitis: Are they related?","volume":"4","author":"Pontari","year":"2006","journal-title":"Curr. Urol. Rep."},{"key":"ref_6","unstructured":"Simpson, D.M., Justin, C.M., and Robert, H.D. (2012). Peripheral and central mechanisms of neuropathic pain. Neuropathic Pain \u2013Mechanisms, Diagnosis and Treatment, Oxford Publisher."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.parkreldis.2011.06.013","article-title":"Update on the nociceptive mechanism hypothesis and related disorders","volume":"17","author":"Aoki","year":"2011","journal-title":"Park. Relat. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.3390\/toxins7062232","article-title":"Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection","volume":"7","author":"Jhang","year":"2015","journal-title":"Toxins"},{"key":"ref_9","first-page":"197","article-title":"Intravesical onabotulinumtoxinA injections for refractory painful bladder syndrome","volume":"15","author":"Chung","year":"2012","journal-title":"Pain Physician"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.urology.2015.12.049","article-title":"Use of Botulinum Toxin in Urologic Diseases","volume":"91","author":"Chermansky","year":"2016","journal-title":"Urology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.3390\/toxins7083127","article-title":"Botulinum toxin for neuropathic pain: A review of the literature","volume":"7","author":"Oh","year":"2015","journal-title":"Toxins"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.3390\/toxins7114519","article-title":"Current status and future directions of botulinum neurotoxins for targeting pain processing","volume":"7","author":"Pellett","year":"2015","journal-title":"Toxins"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/AJP.0000000000000538","article-title":"Efficacy of Intra-Articular Botulinum Toxin in Osteoarticular Joint Pain: A Meta-Analysis of Randomized Controlled Trials","volume":"34","author":"Courseau","year":"2018","journal-title":"Clin. J. Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.3390\/toxins7093818","article-title":"Botulinum Toxin Type a as a Therapeutic Agent against Headache and Related Disorders","volume":"7","author":"Luvisetto","year":"2015","journal-title":"Toxins"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Machado, D., Kumar, A., and Jabbari, B. (2016). Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain. Toxins, 8.","DOI":"10.3390\/toxins8120374"},{"key":"ref_16","first-page":"205","article-title":"Botulinum toxin for the treatment of chronic pain. Review of the evidence","volume":"42","author":"Lotero","year":"2014","journal-title":"Colomb. J. Anesth."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S142","DOI":"10.1097\/00002508-200211001-00005","article-title":"Review of the FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction","volume":"18","author":"Lew","year":"2002","journal-title":"Clin. J. Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10072-017-2884-y","article-title":"Action mechanisms of Onabotulinum toxin-A: Hints for selection of eligible patients","volume":"38","author":"Lovati","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chiu, B., Tai, H.C., Chung, S.D., and Birder, L.A. (2016). Botulinum Toxin A for Bladder Pain Syndrome\/Interstitial Cystitis. Toxins, 8.","DOI":"10.3390\/toxins8070201"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11916-016-0545-0","article-title":"Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States","volume":"20","author":"Patil","year":"2016","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1523\/JNEUROSCI.0375-08.2008","article-title":"Long-distance retrograde effects of botulinum neurotoxin A","volume":"28","author":"Antonucci","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.celrep.2016.06.104","article-title":"Interneuronal Transfer and Distal Action of Tetanus Toxin and Botulinum Neurotoxins A and D in Central Neurons","volume":"16","author":"Vevea","year":"2016","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.toxicon.2017.10.027","article-title":"Direct central nervous system effects of botulinum neurotoxin","volume":"147","author":"Caleo","year":"2018","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Marinelli, S., Vacca, V., Ricordy, R., Uggenti, C., Tata, A.M., Luvisetto, S., and Pavone, F. (2012). The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047977"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0041-0101(99)00153-1","article-title":"Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins","volume":"38","author":"Welch","year":"2000","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1526-4610.2004.04007.x","article-title":"Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: Implications for migraine therapy","volume":"44","author":"Durham","year":"2004","journal-title":"Headache"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/pme.12017","article-title":"Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain","volume":"14","author":"Xiao","year":"2013","journal-title":"Pain Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.juro.2007.07.120","article-title":"Intraprostatic botulinum toxin A injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat","volume":"180","author":"Chuang","year":"2008","journal-title":"J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.urology.2007.04.038","article-title":"Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis","volume":"70","author":"Liu","year":"2007","journal-title":"Urology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.12659\/MSM.897350","article-title":"Intravesical botulinum toxin A injections for bladder pain syndrome\/interstitial cystitis: A systematic review and meta-analysis of controlled studies","volume":"22","author":"Wang","year":"2016","journal-title":"Med. Sci Monit"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s11255-016-1295-y","article-title":"Efficacy and safety of botulinum toxin injection for interstitial cystitis\/bladder pain syndrome: A systematic review and meta-analysis","volume":"48","author":"Shim","year":"2016","journal-title":"Int. Urol. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00192-016-3079-4","article-title":"Intravesical treatment for interstitial cystitis\/painful bladder syndrome: A network meta-analysis","volume":"28","author":"Zhang","year":"2017","journal-title":"Int. Urogynecol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1007\/s00192-010-1162-9","article-title":"Intravesical botulinum toxin A injections in the treatment of painful bladder syndrome\/interstitial cystitis: A systematic review","volume":"21","author":"Tirumuru","year":"2010","journal-title":"Int. Urogynecol. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/S0090-4295(99)80333-1","article-title":"The interstitial cystitis symptom index and problem index","volume":"49","author":"Sant","year":"1997","journal-title":"Urology"},{"key":"ref_35","first-page":"835","article-title":"Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response","volume":"22","author":"Akiyama","year":"2015","journal-title":"Urology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.juro.2017.02.021","article-title":"A prospective, multicenter, double-blinded, randomized trial of bladder instillation of liposome formulation onabotulinumtoxin A for interstitial cystitis\/bladder pain syndrome","volume":"198","author":"Chuang","year":"2017","journal-title":"J. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"El-Bahnasy, A., Farahat, Y., El-Bendary, M., Taha, M.R., El-Damhogy, M., and Mourad, S. (2009). A randomized controlled trial of bacillus Calmette-Guerin and botulinum toxin A for the treatment of refractory interstitial cystitis. UroToday Int. J., 2.","DOI":"10.3834\/uij.1944-5784.2008.12.06"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/nau.20946","article-title":"A Pilot study of botulinum toxin for interstitial cystitis\/painful bladder syndrome","volume":"30","author":"Gottsch","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e335","DOI":"10.1016\/j.juro.2012.02.912","article-title":"Randomized controlled trial for efficacy of botulinum toxin type A in treatment of patients suffering bladder pain syndrome\/interstitial cystitis with Hunners\u2019 Lesions: Preliminary results","volume":"187","author":"Kasyan","year":"2012","journal-title":"J. Urol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/j.1464-410X.2009.08495.x","article-title":"Comparison of botulinum toxin type A injections plus hydrodistention with hydrodistention alone for the treatment of refractory interstitial cystitis\/painful bladder syndrome","volume":"104","author":"Kuo","year":"2009","journal-title":"BJUI Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/nau.22760","article-title":"Intravesical botulinum toxin-A injections reduces bladder pain of interstitial cystitis\/bladder pain syndrome refractory to conventional treatment-A prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial","volume":"35","author":"Kuo","year":"2016","journal-title":"Neurourol. Urodyn."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00192-013-2267-8","article-title":"A multicenter, prospective, randomized, double-blind study to measure the treatment effectiveness of abobotulinum A (AboBTXA) among women with refractory interstitial cystitis\/bladder pain syndrome","volume":"25","author":"Manning","year":"2014","journal-title":"Int. Urogynecol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.juro.2017.10.018","article-title":"Intratrigonal onabotulinumtoxinA improves bladder symptoms and quality of life in patients with bladder pain syndrome\/interstitial cystitis: A pilot, single center, randomized, double-blind, placebo controlled trial","volume":"199","author":"Pinto","year":"2018","journal-title":"J. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1569-9056(10)60630-6","article-title":"A prospective, randomized study of intravesical pentosan polysulfate and botulinum toxin-A for the treatment of painful bladder syndrome\/Interstitial cystitis","volume":"9","author":"Farahat","year":"2010","journal-title":"Eur. Urol. Suppl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0022-5347(17)41529-1","article-title":"Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28\u201329, 1987","volume":"140","author":"Gillenwater","year":"1988","journal-title":"J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13027","DOI":"10.1111\/ijcp.13027","article-title":"A practical approach to the management of nocturia","volume":"71","author":"Oelke","year":"2017","journal-title":"Int. J. Clin. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hsieh, P.F., Chiu, H.C., Chen, K.C., Chang, C.H., and Chou, EC. (2016). Botulinum toxin A for the Treatment of Overactive Bladder. Toxins, 8.","DOI":"10.3390\/toxins8030059"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control. Clin. Trials"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.eururo.2011.07.069","article-title":"Contemporary management of the painful bladder: A systematic review","volume":"61","author":"Giannantoni","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_50","unstructured":"Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, Routledge. [2nd ed.]."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analysis","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"13","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref_54","unstructured":"Jadad, A.R. (1998). Randomised Controlled Trials, Blackwell Publishing."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/9\/510\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:15:24Z","timestamp":1760188524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/9\/510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,30]]},"references-count":54,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["toxins11090510"],"URL":"https:\/\/doi.org\/10.3390\/toxins11090510","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.736553505.793564936","asserted-by":"object"}]},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,30]]}}}