Effect of botulinum neurotoxin on the urinary bladder: novel insights on mechanism of action

Botulinum neurotoxins (BoNTs) recently tarted to be used in common urologic practice for the treatment of neurogenic and non neurogenic detrusor overactivity (DO) refractory to all conventional treatments. The rationale was that botulinum toxin, particularly BoNT type A (BoNT/A), was able to block the presynaptic release of acetylcholine (ACh) from the parasympathetic efferent nerves thus paralyzing the detrusor smooth muscle, an action similar to that performed in skeletal muscles. With the present review we aimed at assessing the state of the art on the mechanisms of function of botulinum toxins in the management of urological dysfunctions. We searched PubMed using the medical subject heading (MeSH) term botulinum toxin in conjunction with any of the following terms: mechanism of action, bladder, afferent and efferent nervous transmission, urothelium and suburothelium, detrusor overactivity. Review articles and published abstracts were identified by limiting for review and abstract, respectively. The reference list of review and original papers were reviewed to identify any missed papers. A similar search strategy was applied in EMBASE using identical EMTREE terms. Recent evidences in in vivo and in in vitro studies suggest that in addition to a direct effect on detrusor motor innervation, BoNT/A also modulates intrinsic bladder reflexes through a multimodal effect on sensory pathways. Such mechanisms may contribute to the efficiency of this treatment and partly explain how it affects abnormal detrusor contractions more markedly than voluntary bladder emptying.