Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation.
OBJECTIVE
To determine the effect of botulinum toxin type A (BTX-A) on the release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from isolated bladder preparations after acute injury with HCl and the induction of cyclophosphamide (CYP)-induced cystitis, as neurogenic inflammation has been increasingly identified in urological disorders such as interstitial cystitis.


METHODS
Adult rats had either an intraperitoneal injection with CYP or saline over a 10-day period to induce chronic bladder inflammation, after which the bladder was harvested, or normal bladder explants were injured acutely with incubation (20 s) in HCl (0.4 m). To measure the effect of BTX-A on the release of neurotransmitters, harvested bladders were incubated in an organ bath containing BTX-A (10 U) or vehicle. Bladders were transferred to a subsequent bath (physiological saline) and incubated for 15 min, and the bathing medium analysed to measure neurotransmitter release, as determined by radioimmunoassay. Bladder specimens from sham treatment, controls and experimental rats were compared histologically.


RESULTS
Acute injury with HCl caused a significantly greater release of both CGRP and SP release (1235 and 1655 pg/g, respectively) than in controls (183 and 449 pg/g, respectively; P < 0.001). This increase in neurotransmitter release was partly inhibited by exposure to BTX-A (870 and 1033 pg/g (P < 0.05 and <0.01). CYP-induced chronic inflammation caused significantly greater release of SP than in the controls (1060 and 605 pg/g, respectively; P < 0.005). Exposure to BTX-A partly inhibited the release of SP after CYP-induced cystitis (709 pg/g, P < 0.05).


CONCLUSIONS
The application of BTX-A inhibits the release of sensory neurotransmitters from isolated bladder preparations in rat bladder models of both acute injury and chronic inflammation, suggesting a potential clinical benefit of BTX-A in the treatment of neurogenic inflammation.
Lucioni
Alvaro
A
Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, 5841S. Maryland Avenue, MC 6038, Chicago, IL 60637, USA. alvarolucioni@hotmail.com
Bales
Gregory T
GT
Lotan
Tamara L
TL
McGehee
Daniel S
DS
Cook
Sean P
SP
Rapp
David E
DE
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects*; D008297:Male; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000188:drug therapy* / Q000473:pathology; D014563:Urodynamics / Q000502:physiology
D009465:Neuromuscular Agents; D013373:Substance P; D019274:Botulinum Toxins, Type A; D015740:Calcitonin Gene-Related Peptide