Mechanisms of prostate atrophy after glandular botulinum neurotoxin type a injection: an experimental study in the rat.
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.
Silva
João
J
Department of Urology, Hospital S. João, Porto, Portugal.
Pinto
Rui
R
Carvallho
Tiago
T
Coelho
Ana
A
Avelino
Antonio
A
Dinis
Paulo
P
Cruz
Francisco
F
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
D009498:Neurotoxins; D010277:Parasympathomimetics; D013566:Sympathomimetics; D018723:Bethanechol; D010656:Phenylephrine; D019274:Botulinum Toxins, Type A