title: Effect of Onabotulinum Toxin A on Substance P and Receptor Neurokinin 1 in the Rat Ventral Prostate.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Urology, Bagcilar Research and Training Hospital, Bagcilar, Istanbul, Turkey.
authors.forename: Omer Onur
authors.initials: OO
authors.lastname: Cakir
authors.affiliation: Department of Urology, Physiology and Bioengineering, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Podlasek
authors.affiliation: Department of Urology, Bagcilar Research and Training Hospital, Bagcilar, Istanbul, Turkey.
authors.forename: Douglas
authors.initials: D
authors.lastname: Wood
authors.affiliation: Department of Physiology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: McKenna
authors.affiliation: Division of Urology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: McVary
keywords: BoNTA; LUTS/BPH; Prostate; Substance P