title: Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014.
abstract: OBJECTIVE
  The use of botulinum toxin A (BoNT/A) is commonplace now in the management of refractory overactive bladder and neurogenic detrusor overactivity (NDO). Despite one formulation now having a license, the full mechanism of action is not fully understood. Furthermore practice varies worldwide in the way the toxin is delivered to the bladder. At the ICI-RS 2014 Meeting in Bristol, UK a Think Tank session was conducted on the topic of "Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder?" This manuscript reflects the Think Tank's summary and opinion.
  
  
  METHODS
  An overview of the existing evidence and consensus regarding mechanism of action and practical aspects of BoNT/A administration was presented. Further avenues of potential research were suggested.
  
  
  RESULTS
  BoNT/A effect in the bladder is complex with likely effects on both efferent and afferent nerves. The site of action is controversial with the relative contribution of the detrusor as opposed to the suburothelial effects remaining unclear and open to further studying. The classical concept of prevention of acetylcholine release in the bladder is not supported by a wealth of evidence on neurotransmitters although co-localization studies have suggested cholinergic nerves are the most affected by BoNT/A. There is more robust evidence for effects on the purinergic system and afferent desensitization and emerging evidence for central effects. A variety of technique studies were presented. OnabotlinumtoxinA has recently been studied in large phase III trials and with this there is a standardized injection technique which is trigone-sparing. The evidence for altering location of injection is mixed with some studies suggesting less voiding dysfunction in bladder base injections alone but others suggesting location of injection does not affect outcomes. Early pilot data and evidence of instillation either with electromotive drug administration (EMDA) or in liposomes were also presented as an alternative to injections.
  
  
  CONCLUSIONS
  The mechanism of action of BoNT/A in the bladder is complex and not fully understood. There is emerging support for its role on afferent mechanisms. The technical aspects of the injection procedure have been standardized to a certain extent but further study is required in larger scale studies to assess minimizing voiding dysfunction, improving tolerability, and assessing alternatives to injections.
authors.affiliation: 2nd Department of Urology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Apostolidis
authors.affiliation: Department of Urology, Maastricht University Medical Centre, Maastricht, Netherlands.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Rahnama'i
authors.affiliation: Department of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fry
authors.affiliation: Department of Urological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Roger
authors.initials: R
authors.lastname: Dmochowski
authors.affiliation: Department of Urology, Guy's Hospital, London, United Kingdom.
authors.forename: Arun
authors.initials: A
authors.lastname: Sahai
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000283:Administration, Intravesical; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D003226:Congresses as Topic; D006801:Humans; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D001750:Urinary Bladder, Neurogenic / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
chemical_list: D065087:Acetylcholine Release Inhibitors; D019274:Botulinum Toxins, Type A
keywords: botulinum toxin; detrusor overactivity; mechanism of action; overactive bladder