title: Mechanisms of prostate atrophy after glandular botulinum neurotoxin type a injection: an experimental study in the rat.
abstract: BACKGROUND
  Previous studies in humans, dogs, and rats have shown that intraprostatic injection of botulinum neurotoxin type A (BoNTA) reduces gland size.
  
  
  OBJECTIVE
  To investigate the role of eventual impairment of sympathetic, parasympathetic, and sensory nerves to gland atrophy after intraprostatic BoNTA administration.
  
  
  METHODS
  Adult male Wistar rats weighing 300-350 g were used.
  
  
  METHODS
  Animals were injected in the prostate ventral lobes with 0.2 ml of saline (n=6) or the same volume containing 10 U BoNTA (BOTOX) (n=18). Six rats treated with BoNTA further received the adrenergic agent phenylephrine (PHE, 0.05 mg/kg per day), six received the cholinergic drug bethanechol (2 mg/kg per day), and six received subcutaneous saline. Animals were sacrificed 1 wk later.
  
  
  METHODS
  Prostates were weighed, fixed, and stained for sympathetic (tyrosine hydroxylase [TH]), parasympathetic (vesicular acetylcholine [ACh] transporter [VAChT]), and sensory nerve (calcitonin gene-related peptide [CGRP]) visualisation. Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labelling (TUNEL) reaction was performed to investigate apoptosis.
  
  
  CONCLUSIONS
  Prostate weight in controls was 1.82+/-0.24 mg/100 g of rat weight. In BoNTA-treated rats, weight decreased to 1.28+/-0.18 mg /100 g of rat weight (p=0.002). In BoNTA plus PHE-treated rats, prostate weight was similar to controls: 1.78+/-0.27 (p=0.87). In rats treated with BoNTA plus bethanechol, weight was less than controls: 1.41+/-0.17 (p=0.01). The number of TH-positive fibres was markedly reduced after BoNTA (p<0.001). VAChT- and CGRP-positive fibres were scarce in controls, preventing further evaluation. Rats treated with BoNTA had more TUNEL-positive cells than controls (p<0.001) and rats treated with BoNTA plus PHE (p<0.001). There were no differences between the BoNTA and BoNTA plus bethanechol groups (p=0.81). Although showing atrophy after BoNTA injection, rat prostates do not develop benign prostatic hyperplasia (BPH). Thus, present findings should be used cautiously to explain prostate atrophy seen in men with BPH treated with BoNTA.
  
  
  CONCLUSIONS
  Prostate atrophy induced by BoNTA in the rat may be the result of sympathetic nerve impairment and decreased adrenergic stimulation of the gland. Data indirectly suggest that sympathetic drive plays a role in prostate-size regulation.
authors.affiliation: Department of Urology, Hospital S. João, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Silva
authors.forename: Rui
authors.initials: R
authors.lastname: Pinto
authors.forename: Tiago
authors.initials: T
authors.lastname: Carvallho
authors.forename: Ana
authors.initials: A
authors.lastname: Coelho
authors.forename: Antonio
authors.initials: A
authors.lastname: Avelino
authors.forename: Paulo
authors.initials: P
authors.lastname: Dinis
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruz
mesh_terms: D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D018723:Bethanechol / Q000008:administration & dosage; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D054313:Drug Agonism; D007267:Injections; D008297:Male; D009498:Neurotoxins / Q000008:administration & dosage; D009929:Organ Size / Q000187:drug effects; D010277:Parasympathomimetics / Q000008:administration & dosage; D010656:Phenylephrine / Q000008:administration & dosage; D011467:Prostate / Q000187:drug effects* / Q000294:innervation / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000473:pathology; D013566:Sympathomimetics
chemical_list: D009498:Neurotoxins; D010277:Parasympathomimetics; D013566:Sympathomimetics; D018723:Bethanechol; D010656:Phenylephrine; D019274:Botulinum Toxins, Type A