{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:04:54Z","timestamp":1774940694856,"version":"3.50.1"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"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>Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic inflammation, and bladder response to BOO. The pathogenesis of BPH involves an imbalance of internal hormones and chronic prostatic inflammation, possibly triggered by prostatic infection, autoimmune responses, neurogenic inflammation, oxidative stress, and autonomic dysfunction. Botulinum toxin A (BoNT-A) is well recognized for its ability to block acetylcholine release at the neuromuscular junction by cleaving synaptosomal-associated proteins. Although current large clinical trials have shown no clinical benefits of BoNT-A for the management of LUTS due to BPH, BoNT-A has demonstrated beneficial effects in certain subsets of BPH patients with LUTS, especially in males with concomitant chronic prostatitis\/chronic pelvic pain syndrome and smaller prostate. We conducted a review of published literature in Pubmed, using Botulinum toxin, BPH, BOO, inflammation, LUTS, and prostatitis as the key words. This article reviewed the mechanisms of BPH pathogenesis and anti-inflammatory effects of BoNT-A. The results suggested that to achieve effectiveness, the treatment of BPH with BoNT-A should be tailored according to more detailed clinical information and reliable biomarkers.<\/jats:p>","DOI":"10.3390\/toxins11090547","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T10:55:21Z","timestamp":1568890521000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Can Botulinum Toxin A Still Have a Role in Treatment of Lower Urinary Tract Symptoms\/Benign Prostatic Hyperplasia Through Inhibition of Chronic Prostatic Inflammation?"],"prefix":"10.3390","volume":"11","author":[{"given":"Bing-Juin","family":"Chiang","sequence":"first","affiliation":[{"name":"College of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan"},{"name":"Department of Urology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan"},{"name":"Department of Life Science, College of Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7165-4771","authenticated-orcid":false,"given":"Hann-Chorng","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Urology, Buddhist Tzu Chi General Hospital, and Tzu Chi University, Hualien 97002, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Hou","family":"Liao","sequence":"additional","affiliation":[{"name":"College of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan"},{"name":"Department of Urology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"ref_1","unstructured":"Gravas, S., Cornu, J.N., Drake, M.J., Gacci, M., Gratzke, C., Herrmann, T.R.W., Mamoulakis, C., Rieken, M., Speakman, M.J., and Tikkinen, K.A.O. (2019, January 01). Management of Non-Neurogenic Male LUTS. Available online: https:\/\/uroweb.org\/guideline\/treatment-of-non-neurogenic-male-luts\/."},{"key":"ref_2","unstructured":"Foster, H.E., Barry, M.J., Gandhi, M.C., Kaplan, S.A., Kohler, T.S., Lerner, L.B., Lightner, D.J., Parsons, J.K., Roehrborn, C.G., and Welliver, C. (2019, January 01). Benign Prostatic Hyperplasia: Surgical Management of Benign Prostatic Hyperplasia\/Lower Urinary Tract Symptoms (2018, Amended 2019). Available online: https:\/\/www.auanet.org\/guidelines\/benign-prostatic-hyperplasia-."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1067\/mob.2002.125704","article-title":"The standardisation of terminology of lower urinary tract function: Report from the Standardisation Sub-committee of the International Continence Society","volume":"187","author":"Abrams","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.eururo.2008.03.109","article-title":"Lower urinary tract symptoms revisited: A broader clinical perspective","volume":"54","author":"Chapple","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1007\/s12325-017-0577-9","article-title":"Prevalence of lower urinary tract symptoms in China, Taiwan, and South Korea: Results from a cross-sectional, population-based study","volume":"34","author":"Chapple","year":"2017","journal-title":"Adv. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.eururo.2006.01.031","article-title":"The association between vascular risk factors and lower urinary tract symptoms in both sexes","volume":"50","author":"Ponholzer","year":"2006","journal-title":"Eur. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1464-410X.2008.07587.x","article-title":"Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: Assessment using colour Doppler ultrasonography","volume":"102","author":"Pinggera","year":"2008","journal-title":"BJU Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0022-5347(01)66307-9","article-title":"Canine bladder blood flow and oxygenation: Changes induced by filling, contraction and outlet obstruction","volume":"155","author":"Azadzoi","year":"1996","journal-title":"J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/00005392-200101000-00072","article-title":"The effect of bladder outflow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs","volume":"165","author":"Greenland","year":"2001","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0022-5347(17)44930-5","article-title":"Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction","volume":"136","author":"Gosling","year":"1986","journal-title":"J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/j.1464-410X.2008.07593.x","article-title":"Immunohistochemical estimation of hypoxia in human obstructed bladder and correlation with clinical variables","volume":"102","author":"Koritsiadis","year":"2008","journal-title":"BJU Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/S0022-5347(17)43675-5","article-title":"Bladder outflow obstruction\u2014A cause of denervation supersensitivity","volume":"138","author":"Speakman","year":"1987","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1016\/S0022-5347(17)37092-1","article-title":"The effect of experimental urethral obstruction and its reversal on changes in passive electrical properties of detrusor muscle","volume":"148","author":"Seki","year":"1992","journal-title":"J. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1046\/j.1464-410x.2000.00611.x","article-title":"The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder","volume":"85","author":"Greenland","year":"2000","journal-title":"BJU Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/cne.903100309","article-title":"Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction","volume":"310","author":"Steers","year":"1991","journal-title":"J. Comp. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1464-410X.1987.tb05033.x","article-title":"Bladder instability and denervation in patients with bladder outflow obstruction","volume":"60","author":"Harrison","year":"1987","journal-title":"Br. J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E524","DOI":"10.5489\/cuaj.1636","article-title":"Obstruction-induced alterations within the urinary bladder and their role in the pathophysiology of lower urinary tract symptomatology","volume":"8","author":"Komninos","year":"2014","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S0022-5347(05)66541-X","article-title":"Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index","volume":"165","author":"Nickel","year":"2001","journal-title":"J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s11934-014-0463-9","article-title":"The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy","volume":"15","author":"Ficarra","year":"2014","journal-title":"Curr. Urol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/pcan.2015.43","article-title":"Metabolic syndrome, inflammation and lower urinary tract symptoms: Possible translational links","volume":"19","author":"He","year":"2016","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1046\/j.1464-410X.1998.0810s1029.x","article-title":"The pathophysiology of lower urinary tract symptoms in the ageing male population","volume":"81","author":"Lepor","year":"1998","journal-title":"Br. J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1210\/jc.2009-1492","article-title":"Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes","volume":"95","author":"Tai","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.eururo.2013.04.042","article-title":"Future direction in pharmacotherapy for non-neurogenic male lower urinary tract symptoms","volume":"64","author":"Soler","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.urols.2015.01.003","article-title":"Significant intravesical prostatic protrusion and prostatic calcification predict unfavorable outcomes of medical treatment for male lower urinary tract symptoms","volume":"27","author":"Kuei","year":"2016","journal-title":"Urol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ucl.2009.07.004","article-title":"Established medical therapy for benign prostatic hyperplasia","volume":"36","author":"Auffenberg","year":"2009","journal-title":"Urol. Clin. N. Am."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0094-0143(21)00961-7","article-title":"Pathology of benign prostatic hyperplasia. Insight into etiology","volume":"17","author":"McNeal","year":"1990","journal-title":"Urol. Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/0090-4295(80)90577-4","article-title":"Human benign prostatic hyperplasia: A stromal disease? New perspectives by quantitative morphology","volume":"16","author":"Rohr","year":"1980","journal-title":"Urology"},{"key":"ref_28","first-page":"92","article-title":"Benign nodular hyperplasia of the prostate; A review","volume":"14","author":"Franks","year":"1953","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0094-0143(21)00978-2","article-title":"Androgen ablation and blockade in the treatment of benign prostatic hyperplasia","volume":"17","author":"McConnell","year":"1990","journal-title":"Urol. Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3109\/13685538.2010.550660","article-title":"Significant association between serum dihydrotestosterone level and prostate volume among Taiwanese men aged 40\u201379 years","volume":"15","author":"Liao","year":"2012","journal-title":"Aging Male"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/j.1939-4640.1991.tb00272.x","article-title":"The pathophysiology of benign prostatic hyperplasia","volume":"12","author":"McConnell","year":"1991","journal-title":"J. Androl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/1097-0045(20000615)44:1<19::AID-PROS3>3.0.CO;2-S","article-title":"Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate","volume":"44","author":"Harris","year":"2000","journal-title":"Prostate"},{"key":"ref_33","first-page":"1","article-title":"5\u03b1-reductase isozymes in the prostate","volume":"25","author":"Zhu","year":"2005","journal-title":"J. Med Sci. (Taipei Taiwan)"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/j.1464-410X.2003.04766.x","article-title":"A randomized placebo-controlled multicentre study to evaluate the safety and efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA chronic nonbacterial prostatitis)","volume":"93","author":"Nickel","year":"2004","journal-title":"BJU Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.eururo.2006.12.011","article-title":"Is benign prostatic hyperplasia (BPH) an immune inflammatory disease?","volume":"51","author":"Kramer","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ucl.2007.09.012","article-title":"Inflammation and benign prostatic hyperplasia","volume":"35","author":"Nickel","year":"2008","journal-title":"Urol. Clin. N. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cca.2017.03.012","article-title":"Elevated insulin and reduced insulin like growth factor binding protein-3\/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia","volume":"469","author":"Sreenivasulu","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15639","DOI":"10.1038\/srep15639","article-title":"Metformin attenuates testosterone-induced prostatic hyperplasia in rats: A pharmacological perspective","volume":"5","author":"Mosli","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15428","DOI":"10.1038\/s41598-017-15832-5","article-title":"Serotonin regulates prostate growth through androgen receptor modulation","volume":"7","author":"Miranda","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/aje\/kwi299","article-title":"Sexually transmitted infections, prostatitis, ejaculation frequency, and the odds of lower urinary tract symptoms","volume":"162","author":"Sutcliffe","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_41","first-page":"1","article-title":"Prostatic inflammation in benign prostatic hyperplasia\u2014The third component?","volume":"1","author":"Nickel","year":"1994","journal-title":"Can. J. Urol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.eururo.2007.11.026","article-title":"The relationship between prostate inflammation and lower urinary tract symptoms: Examination of baseline data from the REDUCE trial","volume":"54","author":"Nickel","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/aje\/kwj258","article-title":"Protective association between nonsteroidal antiinflammatory drug use and measures of benign prostatic hyperplasia","volume":"164","author":"Jacobson","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/pros.20051","article-title":"Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia","volume":"60","author":"Castro","year":"2004","journal-title":"Prostate"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.eururo.2006.07.016","article-title":"Seminal plasma cytokines and chemokines in prostate inflammation: Interleukin 8 as a predictive biomarker in chronic prostatitis\/chronic pelvic pain syndrome and benign prostatic hyperplasia","volume":"51","author":"Penna","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.urology.2007.11.083","article-title":"Elevated epithelial expression of interleukin-8 correlates with myofibroblast reactive stroma in benign prostatic hyperplasia","volume":"72","author":"Schauer","year":"2008","journal-title":"Urology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.4049\/jimmunol.0801875","article-title":"Human benign prostatic hyperplasia stromal cells as inducers and targets of chronic immuno-mediated inflammation","volume":"182","author":"Penna","year":"2009","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1365-2605.2009.00972.x","article-title":"Chronic inflammation in the pathogenesis of benign prostatic hyperplasia","volume":"33","author":"Fibbi","year":"2010","journal-title":"Int. J. Androl."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.eururo.2007.06.038","article-title":"Inflammation and chronic prostatic diseases: Evidence for a link?","volume":"52","author":"Sciarra","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/pros.20896","article-title":"The vitamin D receptor agonist elocalcitol inhibits IL-8-dependent benign prostatic hyperplasia stromal cell proliferation and inflammatory response by targeting the RhoA\/Rho kinase and NF-kappaB pathways","volume":"69","author":"Penna","year":"2009","journal-title":"Prostate"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1016\/j.ijantimicag.2007.08.028","article-title":"Epidemiology of prostatitis","volume":"31","author":"Krieger","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_52","first-page":"217","article-title":"Studies on the prostate and testis as immunologically privileged sites","volume":"61","author":"Whitmore","year":"1977","journal-title":"Cancer Treat. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/S0022-5347(01)66974-X","article-title":"Autoantibodies to prostate specific antigen in patients with benign prostatic hyperplasia","volume":"154","author":"Zisman","year":"1995","journal-title":"J. Urol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.clim.2005.03.011","article-title":"Presence of INF\u03b3-secreting lymphocytes specific to prostate antigens in a group of chronic prostatitis patients","volume":"116","author":"Motrich","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/1097-0045(20000615)44:1<49::AID-PROS7>3.0.CO;2-7","article-title":"PSA is a candidate self-antigen in autoimmune chronic prostatitis\/chronic pelvic pain syndrome","volume":"44","author":"Ponniah","year":"2000","journal-title":"Prostate"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0090-4295(01)01597-7","article-title":"Nerve growth factor and chronic prostatitis\/chronic pelvic pain syndrome","volume":"59","author":"Miller","year":"2002","journal-title":"Urology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1128\/iai.59.12.4443-4449.1991","article-title":"Isolated hepatic granulomas from mice infected with Schistosoma mansoni contain nerve growth factor","volume":"59","author":"Varilek","year":"1991","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0014-5793(86)80428-8","article-title":"Nerve growth factor induces mast cell degranulation without changing intracellular calcium levels","volume":"198","author":"Mazurek","year":"1986","journal-title":"FEBS Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"59156","DOI":"10.18632\/oncotarget.19465","article-title":"Infiltrating mast cells enhance benign prostatic hyperplasia through IL-6\/STAT3\/Cyclin D1 signals","volume":"8","author":"Ou","year":"2017","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/337362a0","article-title":"Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons","volume":"337","author":"Lindsay","year":"1989","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"F840","DOI":"10.1152\/ajprenal.00187.2002","article-title":"Substance P via NK1 receptor facilitates hyperactive bladder afferent signaling via action of ROS","volume":"284","author":"Chien","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1113\/JP277452","article-title":"Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation","volume":"597","author":"Funahashi","year":"2019","journal-title":"J. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/pros.23100","article-title":"Oxidative stress promotes benign prostatic hyperplasia","volume":"76","author":"Vital","year":"2016","journal-title":"Prostate"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"105735","DOI":"10.18632\/oncotarget.22395","article-title":"Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats","volume":"8","author":"Chiang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Dearakhshandeh, N., and Mogheiseh, A. (2019). Changes in the oxidative stress factors and inflammatory proteins following the treatment of BPH-induced dogs with an anti-proliferative agent called tadalafil. J. Vet. Pharmacol. Ther.","DOI":"10.1111\/jvp.12805"},{"key":"ref_66","first-page":"46","article-title":"Inflammation and prostate cancer","volume":"13","author":"Sugar","year":"2006","journal-title":"Can. J. Urol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0302-2838(02)00548-1","article-title":"Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: A retrospective analysis","volume":"43","author":"Gentile","year":"2003","journal-title":"Eur. Urol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1097\/01.ju.0000173072.73702.64","article-title":"Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia","volume":"174","author":"McVary","year":"2005","journal-title":"J. Urol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1210\/en.2008-1782","article-title":"A signaling network in phenylephrine-induced benign prostatic hyperplasia","volume":"150","author":"Kim","year":"2009","journal-title":"Endocrinology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/pros.10267","article-title":"Norepinephrine activates P44 and P42 MAPK in human prostate stromal and smooth muscle cells but not in epithelial cells","volume":"56","author":"Kanagawa","year":"2003","journal-title":"Prostate"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"s740","DOI":"10.2741\/1093","article-title":"Regulation of stromal proliferation, growth arrest, differentiation and apoptosis in benign prostatic hyperplasia by TGF-beta","volume":"8","author":"Huang","year":"2003","journal-title":"Front. Biosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0968-0004(02)02177-1","article-title":"Botulinum and tetanus neurotoxins: Structure, function and therapeutic utility","volume":"27","author":"Turton","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/S0022-5347(05)00318-6","article-title":"Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland","volume":"175","author":"Chuang","year":"2006","journal-title":"J. Urol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.eururo.2007.03.002","article-title":"Effects of botulinum toxin A on the contractile function of dog prostate","volume":"52","author":"Lin","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chuang, Y.C., Tu, C.H., Huang, C.C., Lin, H.J., Chiang, P.H., Yoshimura, N., and Chancellor, M.B. (2006). Intraprostatic injection of botulinum toxin type-A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs. BMC Urol., 6.","DOI":"10.1186\/1471-2490-6-12"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/j.1464-410X.2006.06479.x","article-title":"Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia","volume":"98","author":"Chuang","year":"2006","journal-title":"BJU Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1517\/13543784.10.8.1531","article-title":"Botulinum toxin therapy for pain and inflammatory disorders: Mechanisms and therapeutic effects","volume":"10","author":"Borodic","year":"2001","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12640-013-9447-7","article-title":"Anti-inflammatory effects of botulinum toxin type A in a complete Freund\u2019s adjuvant-induced arthritic knee joint of hind leg on rat model","volume":"26","author":"Yoo","year":"2014","journal-title":"Neurotox. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jdermsci.2018.12.004","article-title":"Botulinum toxin blocks mast cells and prevents rosacea like inflammation","volume":"93","author":"Choi","year":"2019","journal-title":"J. Dermatol. Sci."},{"key":"ref_80","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_81","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/01.ju.0000137844.77524.97","article-title":"Intravesical botulinum toxin A administration produces analgesia against acetic acid induced bladder pain responses in rats","volume":"172","author":"Chuang","year":"2004","journal-title":"J. Urol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neuro.2005.01.017","article-title":"Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A","volume":"26","author":"Aoki","year":"2005","journal-title":"Neurotoxicology"},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"9072","DOI":"10.1038\/srep09072","article-title":"Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury","volume":"5","author":"Uchiyama","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"L1094","DOI":"10.1152\/ajplung.2001.280.6.L1094","article-title":"IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways","volume":"280","author":"Schraufstatter","year":"2001","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.urology.2004.10.077","article-title":"Prostate botulinum A toxin injection\u2014An alternative treatment for benign prostatic obstruction in poor surgical candidates","volume":"65","author":"Kuo","year":"2005","journal-title":"Urology"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Silva, J., Pinto, R., Carvalho, T., Botelho, F., Silva, P., Oliveira, R., Silva, C., Cruz, F., and Dinis, P. (2009). Intraprostatic botulinum toxin type A injection in patients with benign prostatic enlargement: Duration of the effect of a single treatment. BMC Urol., 9.","DOI":"10.1186\/1471-2490-9-9"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0090-4295(03)00477-1","article-title":"Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: Results of a randomized, placebo-controlled study","volume":"62","author":"Maria","year":"2003","journal-title":"Urology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.urology.2005.04.029","article-title":"Botulinum toxin type A improves benign prostatic hyperplasia symptoms in patients with small prostates","volume":"66","author":"Chuang","year":"2005","journal-title":"Urology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.urology.2008.08.475","article-title":"Relief by botulinum toxin of lower urinary tract symptoms owing to benign prostatic hyperplasia: Early and long-term results","volume":"73","author":"Brisinda","year":"2009","journal-title":"Urology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.juro.2014.02.004","article-title":"A multicenter, randomized, double-blind, placebo controlled study of onabotulinumtoxinA 200 U to treat lower urinary tract symptoms in men with benign prostatic hyperplasia","volume":"192","author":"McVary","year":"2014","journal-title":"J. Urol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.eururo.2012.10.005","article-title":"A randomized double-blind placebo-controlled phase 2 dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia","volume":"63","author":"Marberger","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11255-015-1153-3","article-title":"Efficacy and safety of botulinum toxin injection for benign prostatic hyperplasia: A systematic review and meta-analysis","volume":"48","author":"Shim","year":"2016","journal-title":"Int. Urol. Nephrol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/nau.21142","article-title":"The use of botulinum toxin in benign prostatic hyperplasia","volume":"31","author":"Marchal","year":"2012","journal-title":"Neurourol. Urodyn."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.eururo.2013.10.033","article-title":"An updated systematic review and statistical comparison of standardised mean outcomes for the use of botulinum toxin in the management of lower urinary tract disorders","volume":"65","author":"Mangera","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.eururo.2011.07.001","article-title":"Contemporary management of lower urinary tract disease with botulinum toxin A: A systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA)","volume":"60","author":"Mangera","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.aju.2015.01.001","article-title":"Intraprostatic injection of botulinum toxin-A in patients with refractory chronic pelvic pain syndrome: The transurethral vs. transrectal approach","volume":"13","author":"Tawfik","year":"2015","journal-title":"Arab J. Urol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/bju.12951","article-title":"Transurethral intraprostatic injection of botulinum neurotoxin type A for the treatment of chronic prostatitis\/chronic pelvic pain syndrome: Results of a prospective pilot double-blind and randomized placebo-controlled study","volume":"116","author":"Falahatkar","year":"2015","journal-title":"BJU Int."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/9\/547\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:21:54Z","timestamp":1760188914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/9\/547"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,19]]},"references-count":98,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["toxins11090547"],"URL":"https:\/\/doi.org\/10.3390\/toxins11090547","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,19]]}}}