Can Botulinum Toxin A Still Have a Role in Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Through Inhibition of Chronic Prostatic Inflammation?

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2019 Sep 25

PMID 31546892

Citations 5

Authors

Bing-Juin Chiang

Hann-Chorng Kuo

Chun-Hou Liao

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Speakman M, Brading A, Gilpin C, Dixon J, Gilpin S, Gosling J . Bladder outflow obstruction--a cause of denervation supersensitivity. J Urol. 1987; 138(6):1461-6. DOI: 10.1016/s0022-5347(17)43675-5. View

Ponholzer A, Temml C, Wehrberger C, Marszalek M, Madersbacher S . The association between vascular risk factors and lower urinary tract symptoms in both sexes. Eur Urol. 2006; 50(3):581-6. DOI: 10.1016/j.eururo.2006.01.031. View

Sugar L . Inflammation and prostate cancer. Can J Urol. 2006; 13 Suppl 1:46-7. View

McVary K, Rademaker A, Lloyd G, Gann P . Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2005; 174(4 Pt 1):1327-433. DOI: 10.1097/01.ju.0000173072.73702.64. View

Lindsay R, Harmar A . Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature. 1989; 337(6205):362-4. DOI: 10.1038/337362a0. View

Steers W, Ciambotti J, Etzel B, Erdman S, de Groat W . Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction. J Comp Neurol. 1991; 310(3):401-10. DOI: 10.1002/cne.903100309. View

Chuang Y, Chiang P, Huang C, Yoshimura N, Chancellor M . Botulinum toxin type A improves benign prostatic hyperplasia symptoms in patients with small prostates. Urology. 2005; 66(4):775-9. DOI: 10.1016/j.urology.2005.04.029. View

Ou Z, He Y, Qi L, Zu X, Wu L, Cao Z . Infiltrating mast cells enhance benign prostatic hyperplasia through IL-6/STAT3/Cyclin D1 signals. Oncotarget. 2017; 8(35):59156-59164. PMC: 5601722. DOI: 10.18632/oncotarget.19465. View

Choi J, Werbel T, Wang Z, Wu C, Yaksh T, Di Nardo A . Botulinum toxin blocks mast cells and prevents rosacea like inflammation. J Dermatol Sci. 2019; 93(1):58-64. PMC: 7680644. DOI: 10.1016/j.jdermsci.2018.12.004. View

10.

Sreenivasulu K, Nandeesha H, Dorairajan L, Rajappa M, Vinayagam V . Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia. Clin Chim Acta. 2017; 469:37-41. DOI: 10.1016/j.cca.2017.03.012. View

11.

El-Enen M, Abou-Farha M, El-Abd A, El-Tatawy H, Tawfik A, El-Abd S . Intraprostatic injection of botulinum toxin-A in patients with refractory chronic pelvic pain syndrome: The transurethral vs. transrectal approach. Arab J Urol. 2015; 13(2):94-9. PMC: 4561927. DOI: 10.1016/j.aju.2015.01.001. View

12.

Schraufstatter I, Chung J, Burger M . IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways. Am J Physiol Lung Cell Mol Physiol. 2001; 280(6):L1094-103. DOI: 10.1152/ajplung.2001.280.6.L1094. View

13.

Mangera A, Andersson K, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A . Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA). Eur Urol. 2011; 60(4):784-95. DOI: 10.1016/j.eururo.2011.07.001. View

14.

Falahatkar S, Shahab E, Gholamjani Moghaddam K, Kazemnezhad E . 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. BJU Int. 2014; 116(4):641-9. DOI: 10.1111/bju.12951. View

15.

McConnell J . The pathophysiology of benign prostatic hyperplasia. J Androl. 1991; 12(6):356-63. View

16.

Mosli H, Esmat A, Atawia R, Shoieb S, Mosli H, Abdel-Naim A . Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective. Sci Rep. 2015; 5:15639. PMC: 4616049. DOI: 10.1038/srep15639. View

17.

Harrison S, Hunnam G, Farman P, Ferguson D, Doyle P . Bladder instability and denervation in patients with bladder outflow obstruction. Br J Urol. 1987; 60(6):519-22. DOI: 10.1111/j.1464-410x.1987.tb05033.x. View

18.

Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U . The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Am J Obstet Gynecol. 2002; 187(1):116-26. DOI: 10.1067/mob.2002.125704. View

19.

ROHR H, Bartsch G . Human benign prostatic hyperplasia: a stromal disease? New perspectives by quantitative morphology. Urology. 1980; 16(6):625-33. DOI: 10.1016/0090-4295(80)90577-4. View

20.

Koritsiadis G, Stravodimos K, Koutalellis G, Agrogiannis G, Koritsiadis S, Lazaris A . Immunohistochemical estimation of hypoxia in human obstructed bladder and correlation with clinical variables. BJU Int. 2008; 102(3):328-32. DOI: 10.1111/j.1464-410X.2008.07593.x. View