Proposed mechanism of action of botulinum toxin type A (BoNTA) injected into the overactive bladder wall.

It has been proposed that a complex system of interactions exists between the release of neurotransmitters and actions on respective receptors located on the urothelium and suburothelium, corresponding to pathways of bladder mechanosensation. All connections identified by arrows are thought to be upregulated in detrusor overactivity. BoNTA may exert a multimodal effect on those pathways via multiple inhibition of the vesicular release of neurotransmitters and neuropeptides by the urothelium and suburothelial nerves and reduction of the axonal expression of soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)-complex–dependent proteins that are thought to be involved in bladder mechanosensation. 

bl = basal lamina of urothelium; mf = myofibroblast layer; det = detrusor muscle; TRPV1 = transient receptor potential vanilloid 1; P2X3 = ionotropic purinergic receptor type 3; P2Y = metabotropic purinergic receptors; M2/M3 = muscarinic acetylcholine receptors types 2 and 3; NK1 = neurokinin receptor type 1 (SP receptor); SP = substance P; NGF = nerve growth factor; ACh = acetylcholine; ATP = adenosine triphosphate.