Understanding the Role of Botulinum Toxin A in the Treatment of the Overactive Bladder—More than Just Muscle Relaxation  Apostolos Apostolidis, Axel Haferkamp, K. Roger Aoki  European Urology Supplements  Volume 5, Issue 11, Pages 670-678 (July 2006) DOI: 10.1016/j.eursup.2006.05.006 Copyright © 2006 European Association of Urology Terms and Conditions

Fig. 1 Bladder signalling in health. In healthy patients, sensation of bladder fullness is conveyed by the mechanosensitive Aδ afferent axons, whereas the primarily nociceptive C-fibres do not normally respond to mechanical distension and remain quiescent. Stimuli associated with the sensation of bladder fullness then ascend via the spinal cord to an integrative brain centre, the periaqueductal grey (PAG), and are relayed to the pontine micturition centre (PMC), which promotes micturition via excitatory parasympathetic outflow to the bladder. European Urology Supplements 2006 5, 670-678DOI: (10.1016/j.eursup.2006.05.006) Copyright © 2006 European Association of Urology Terms and Conditions

Fig. 2 Bladder signalling in neurogenic detrusor overactivity. Following the disruption of the spinobulbospinal pathways, as in conditions associated with spinal neurogenic detrusor overactivity, capsaicin-sensitive C-fibre afferents in the suburothelium undergo hypertrophy and display increased excitability, consequently becoming sensitive to mechanical stimuli. Such changes lead to increased afferent firing to the spinal cord during bladder distension, increased parasympathetic input to the bladder and, thus, detrusor overactivity. European Urology Supplements 2006 5, 670-678DOI: (10.1016/j.eursup.2006.05.006) Copyright © 2006 European Association of Urology Terms and Conditions

Fig. 3 Intradetrusor BoNT/A injections produced progressive decrease and eventual ‘normalisation’ of mean P2X3 (a) and TRPV1 (b) immunoreactivity in suburothelial nerve fibres at 16 weeks after successful treatment in a group of patients suffering from intractable NDO or IDO. European Urology Supplements 2006 5, 670-678DOI: (10.1016/j.eursup.2006.05.006) Copyright © 2006 European Association of Urology Terms and Conditions

Fig. 4 Proposed ‘cascade’ mechanism of action of intravesically injected BoNT/A via multiple inhibition of the vesicular release of neurotransmitters and neuropeptides by the urothelium and suburothelial nerves and reduction of the axonal expression of SNARE-complex dependent proteins that are thought to be involved in bladder mechanosensation (reproduced with permission from Eur Urol 2006;49:644–650). European Urology Supplements 2006 5, 670-678DOI: (10.1016/j.eursup.2006.05.006) Copyright © 2006 European Association of Urology Terms and Conditions