Lack of Ultrastructural Detrusor Changes Following Endoscopic Injection of Botulinum Toxin Type A in Overactive Neurogenic Bladder

Haferkamp, Axel; Schurch, Brigitte; Reitz, André; Krengel, Ute; Grosse, Joachim; Kramer, Guus; Schumacher, Stefan; Bastian, Patrick J.; Büttner, Reinhard; Müller, Stefan; Stöhrer, M.

doi:10.1016/j.eururo.2004.07.011

Cited by 183 publications

(88 citation statements)

References 20 publications

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“…In that way, BTX prevents normal vesicle docking and fusion to the presynaptic plasma membrane, and inhibits ACh release at the presynaptic cholinergic neuromuscular junction (Haferkamp et al 2004). Probably due to the toxin mechanism of action, the most distinct changes observed in this study after BTX treatment concerned the number of VAChT-immunopositive fibers.…”

Section: H/npymentioning

confidence: 74%

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall

Lepiarczyk¹,

Bossowska²,

Kaleczyc³

et al. 2011

Polish Journal of Veterinary Sciences

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Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n=6) and in the pigs (n=6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DβH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DβH/NPY-or DβH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

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Section: H/npymentioning

confidence: 74%

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall

Lepiarczyk¹,

Bossowska²,

Kaleczyc³

et al. 2011

Polish Journal of Veterinary Sciences

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show abstract

“…Only one study, by Haferkamp and colleagues, 94 has examined ultrastructural changes in overactive human detrusor tissue after BTX-A injection. They collected 30 biopsy specimens from 24 patients with neurogenic overactive bladder, before and 3 months after BTX-A injection and during the wearing-off phase of the toxin's efficacy.…”

Section: Histological Effects Of Btx-a Injectionmentioning

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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“…BTX-A intravesical injections have been demonstrated to be an effective treatment for both neurogenic and nonneurogenic detrusor overactivity [3,4], without producing any consistent axonal sprouting within the detrusor muscle [5].…”

Section: Introductionmentioning

confidence: 99%

Botulinum A Toxin Intravesical Injections in the Treatment of Painful Bladder Syndrome: A Pilot Study

et al. 2006

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e u r o p e a n u r o l o g y 4 9 ( 2 0 0 6 ) 7 0 4 -7 0 9 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Article info AbstractObjective: We evaluated the efficacy and tolerability of botulinum A toxin (BTX-A) intravesical injections in patients affected by painful bladder syndrome with increased urinary frequency, refractory to conventional treatment modalities. Methods: Twelve women and two men were prospectively included in the study. Under short general anaesthesia patients were given injections of 200 U of commercially available BTX-A diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the trigone and bladder floor under cystoscopic control. Voiding chart, the Visual Analog Scale (VAS) for pain, and urodynamics were performed before treatment and 1 and 3 mo afterward. Results: Overall, 12 patients (85.7%) reported subjective improvement at 1 and 3 mo follow-up. The mean VAS score was significantly reduced at 1 and 3 mo after treatment ( p < 0.05 for both); at the same time points daytime and nighttime urinary frequency significantly decreased ( p < 0.01 and p < 0.05, respectively), and bladder cystometric capacity significantly increased ( p < 0.01). Two patients reported incomplete bladder emptying. We did not detect any systemic side effects during or after treatment. Conclusions:The results of this pilot study indicate that BTX-A intravesical injections are effective in the short-term management of painful bladder syndrome. By modulating afferent C-fiber activity within the bladder walls, BTX-A significantly improves urodynamic parameters and reduces bladder pain and urinary frequency. #

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Lack of Ultrastructural Detrusor Changes Following Endoscopic Injection of Botulinum Toxin Type A in Overactive Neurogenic Bladder

Cited by 183 publications

References 20 publications

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall

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

Botulinum A Toxin Intravesical Injections in the Treatment of Painful Bladder Syndrome: A Pilot Study

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