Mechanisms of action of intravesical botulinum treatment in refractory detrusor overactivity

Urinary retention is one of a multitude of autonomic deficits resulting from acute botulism (oral botulinum intoxication). The powerful influence of botulinum-A neurotoxin (BoNT-A) on autonomic function has now been harnessed to the benefit of patients with detrusor overactivity (DO), by injecting the agent intramurally, with consequent improvement in urodynamic and clinical variables. Nonetheless, the complexity of bladder cellular physiology and putative mechanisms underlying the pathophysiological basis of DO even now render the precise mechanisms of clinical response to intravesical BoNT-A uncertain. In this review, the processes by which BoNT-A affects nerve function and the state-of-the-art in the physiological understanding of bladder dysfunction are discussed together, conveying how much must be reckoned when attempting to understand the mechanisms by which this powerful agent can improve refractory and bothersome DO.