Effect of Botulinum Toxin A on the Autonomic Nervous System of the Rat Lower Urinary Tract

Smith, Christopher P.; Franks, Michael; McNeil, Brian K.; Ghosh, Rudrani; Groat, William C. de; Chancellor, Michael B.; Somogyi, George T.

doi:10.1097/01.ju.0000049202.56189.54

Cited by 153 publications

(101 citation statements)

References 20 publications

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“…19 The proposed mechanisms of BoNT-A on neuronal hyperactivity are inhibition of vesicular release of excitatory neurotransmitters and neuropeptides, such as ACh, norepinephrine, adenosine triphosphate, nerve growth factor and substance P, as well as suppression of the axonal expression of the transient receptor potential vanilloid 1 channel and purinergic receptors, from the urothelium and suburothelial nerve endings. [19][20][21] In the present study, we delivered BoNT-A not into the detrusor layer, but mainly into the suburothelial layer, and achieved symptom relief in patients with refractory IC.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

et al. 2015

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Objectives: To determine whether botulinum toxin type A can represent an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies. Methods: This is a single-center, prospective, open labeled, randomized comparative study. Patients with refractory interstitial cystitis were randomly divided into two groups: immediate injection (group A) or 1-month delayed injection (group B) of botulinum toxin type A after allocation. The rate of treatment response (global response assessment ≥+1: slightly improved), and changes in symptom scores and frequency volume chart variables were compared between groups 1 month after allocation. Using subjects of both groups as a single cohort, predictive factors for treatment response at 1 month post-injection and the duration of response were explored. Results: A total of 34 patients (group A n = 18, group B n = 16) were allocated. The response rate was significantly higher in group A than group B (72.2% vs 25.0%, P = 0.01). All symptom measures showed significant improvement in group A than group B. When both groups were combined as a single cohort, the response rate was 73.5% at 1 month, 58.8% at 3 months, 38.2% at 6 months and 20.6% at 12 months. The mean duration of response was 5.4 months. Multivariate analysis showed that past exposure to hydrodistension more than three times correlated with better outcomes. Conclusions: Botulinum toxin type A injection could be an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies, especially for those who have received repeated hydrodistensions and transurethral fulguration.

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Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

et al. 2015

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“…A more intriguing hypothesis comes from the observation that BTX-A inhibits not only the release of ACh and noradrenaline, 16 but also that of ATP, substance P and CGRP, from the detrusor muscle and urothelium. 17 ACh, noradrenaline and ATP have been demonstrated to decrease NGF production at the level of the detrusor muscle and urothelium.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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.

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“…If high doses of BTX-A are used, near-complete neuromuscular blockade of the detrusor results in impaired voiding and/or urinary retention. 4,[60][61][62][63] However, there is no compelling evidence at this time that BTX-A acts on the detrusor smooth muscle.…”

Section: Action On Striated Versus Smooth Musclementioning

confidence: 99%

“…63 ATP has also been implicated as a neurotransmitter in the generation of unstable contractions in idiopathic detrusor overactivity. [67][68][69] Animal studies of bladder strips from guinea pigs 70 and rats 71 indicate that BTX-A inhibits the release of both acetylcholine and ATP, providing a rationale for its possible use in treating patients with idiopathic detrusor overactivity.…”

Section: Effects On Acetylcholine and Atp Releasementioning

confidence: 99%

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

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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Effect of Botulinum Toxin A on the Autonomic Nervous System of the Rat Lower Urinary Tract

Abstract: These data indicate that the clinical effects of botulinum toxin A on the lower urinary tract may vary depending on the site of injection and level of nerve activity.

Cited by 153 publications

References 20 publications

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

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

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

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