Omer Onur Cakir1, Carol A Podlasek2, Douglas Wood1, Kevin E McKenna3, Kevin T McVary4. 1. Department of Urology, Bagcilar Research and Training Hospital, Bagcilar, Istanbul, Turkey. 2. Department of Urology, Physiology and Bioengineering, University of Illinois College of Medicine, Chicago, IL 60612, USA. 3. Department of Physiology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. 4. Division of Urology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
Abstract
INTRODUCTION: The objective of this work is to examine if sensory innervation impacts lower urinary tract symptoms (LUTS). Onabotulinum toxin A (BoNTA) has been used for the treatment of overactive and neurogenic bladder and as a treatment for LUTS secondary to benign prostatic hyperplasia (BPH). The mechanism of how BoNTA impacts LUTS/BPH is unclear. In rats, BoNTA injection causes prostate denervation, apoptosis and atrophy. In clinical trials reduced prostate size and LUTS are observed inconsistently, suggesting a neurologic component. We will examine if BoNTA treatment inhibits substance P production in sensory nerve fibers in the rat prostate. METHODS: Twenty Sprague Dawley rats were divided into four groups including 1X PBS (control, n=6), 2.5 units Onabotulinum toxin A (BoNTA, n=6), 5 units BoNTA (n=6) injected into both lobes of the ventral prostate (VP) and sham surgery (n=2). Rats were Euthanized after one week. Substance P and its receptor neurokinin 1 localization and quantification were performed by counting the number of stained neurons and nerve bundles, by semi-quantitative immunohistochemical analysis and by western analysis. RESULTS: Substance P was localized in neuronal axons and bundles in the stroma of the VP but not in the epithelium. Receptor neurokinin 1 was identified in neuronal bundles of the stroma and in columnar epithelium of the VP ducts. Substance P decreased ~90% after BoNTA treatment (p=0.0001) while receptor neurokinin 1 did not change by IHC (p=0.213) or Western (p=0.3675). CONCLUSIONS: BoNTA treatment decreases substance P in the rat VP.
INTRODUCTION: The objective of this work is to examine if sensory innervation impacts lower urinary tract symptoms (LUTS). Onabotulinum toxin A (BoNTA) has been used for the treatment of overactive and neurogenic bladder and as a treatment for LUTS secondary to benign prostatic hyperplasia (BPH). The mechanism of how BoNTA impacts LUTS/BPH is unclear. In rats, BoNTA injection causes prostate denervation, apoptosis and atrophy. In clinical trials reduced prostate size and LUTS are observed inconsistently, suggesting a neurologic component. We will examine if BoNTA treatment inhibits substance P production in sensory nerve fibers in the rat prostate. METHODS: Twenty Sprague Dawley rats were divided into four groups including 1X PBS (control, n=6), 2.5 units Onabotulinum toxin A (BoNTA, n=6), 5 units BoNTA (n=6) injected into both lobes of the ventral prostate (VP) and sham surgery (n=2). Rats were Euthanized after one week. Substance P and its receptor neurokinin 1 localization and quantification were performed by counting the number of stained neurons and nerve bundles, by semi-quantitative immunohistochemical analysis and by western analysis. RESULTS: Substance P was localized in neuronal axons and bundles in the stroma of the VP but not in the epithelium. Receptor neurokinin 1 was identified in neuronal bundles of the stroma and in columnar epithelium of the VP ducts. Substance P decreased ~90% after BoNTA treatment (p=0.0001) while receptor neurokinin 1 did not change by IHC (p=0.213) or Western (p=0.3675). CONCLUSIONS: BoNTA treatment decreases substance P in the ratVP.
Authors: Paul D Walden; Dorene Marinese; Dinesh Srinivasan; Elda Tzoumaka; Harley T Syyong; Anthony P D W Ford; Anindya Bhattacharya Journal: Prostate Date: 2005-06-01 Impact factor: 4.104
Authors: João Silva; Rui Pinto; Tiago Carvallho; Ana Coelho; Antonio Avelino; Paulo Dinis; Francisco Cruz Journal: Eur Urol Date: 2008-07-15 Impact factor: 20.096