Botulinum-A Toxin Injections Into the Detrusor Muscle Decrease Nerve Growth Factor Bladder Tissue Levels in Patients With Neurogenic Detrusor Overactivity

Abstract

Purpose:We investigated the effects of BTX-A on visceral afferent nerve transmission by measuring bladder tissue NGF levels in patients with neurogenic detrusor overactivity before and after intravesical treatment with BTX-A. We also compared the bladder tissue NGF content with clinical and urodynamic data. Materials and Methods: A total of 23 patients underwent clinical evaluation and urodynamics with detection of the UDC threshold, maximum pressure and maximum cystometric capacity before, and at the 1 and 3-month followups. Endoscopic bladder wall biopsies were also obtained at the same time points. NGF levels were measured in tissue homogenate by enzyme-linked immunosorbent assay (Promega, Madison, Wisconsin). Results: At 1 and 3 months mean catheterization and incontinent episodes were significantly decreased (p Ͻ0.05 and Ͻ0.001, respectively). On urodynamics we detected a significant increase in the UDC threshold and maximum cystometric capacity, and a significant decrease in UDC maximum pressure at the 1 and 3-month followups compared to baseline (each p Ͻ0.001).At the same time points we detected a significant decrease in NGF bladder tissue content (each p Ͻ0.02). Conclusions: BTX-A intravesical treatment induces a state of NGF deprivation in bladder tissue that persists at least up to 3 months. As caused by BTX-A, the decrease in acetylcholine release at the presynaptic level may induce a decrease in detrusor contractility and in NGF production by the detrusor muscle. Alternatively BTX-A can decrease the bladder level of neurotransmitters that normally modulate NGF production and release.

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

“…Intravesical BTX-A injection lowers the NGF content in the bladder tissue of patients with neurogenic detrusor overactivity; however, it is unknown whether reduced bladder NGF results from decreased production, reduced uptake or a combination of both. 90 …”

Botulinum A Toxin Intravesical Injections in the Treatment of Refractory Overactive Bladder in Patients with Parkinson's Disease

“…In vitro and in vivo experimental studies suggest that the long-lasting effect of the BoNT/A injection in the detrusor muscle could be attributed to the lack of axonal sprouting, as observed in detrusor biopsies after toxin injection (Haferkamp et al, 2004). Studies on biopsies from patients with neurogenic overactive bladder who receive an intradetrusor BoNT/A injection (Apostolidis et al, 2006;Giannantoni et al, 2006), however, have shown decreased levels of sensory receptors P2X3, TRPV1 and NGF, thereby suggesting that BoNT/A may act by reducing the afferent nervous transmission.…”

“…In both neural and bladder tissue, BoNT/A affected the release of numerous sensory transmitters other than ACh, including adenosine triphosphate (ATP), substance P, calcitonin gene related peptide (CGRP), and glutamate. BoNT/A may also interfere with vesicle trafficking (Apostolidis et al, 2006), expression of sensory receptors (Apostolidis et al, 2005) and nerve growth factor (NGF) in the bladder wall (Giannantoni et al, 2006). It is therefore likely 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.…”

Neural Control of the Lower Urinary Tract

“…NGF levels can be reduced along with symptom improvement after intradetrusor botulinum toxin treatment (231,385). Animal studies also demonstrated that the production of neurotrophic factors including NGF increases in the bladder after SCI (661) and chronic administration of NGF into the spinal cord or into the bladder wall in rats induces bladder overactivity and increases excitability of bladder afferent neurons (366,698,740).…”