Botulinum Neurotoxin Serotype A Suppresses Neurotransmitter Release from Afferent as Well as Efferent Nerves in the Urinary Bladder

Ikeda, Youko; Zabbarova, Irina; Birder, Lori A.; Groat, William C. de; McCarthy, Carly; Hanna-Mitchell, Ann T.; Kanai, Anthony

doi:10.1016/j.eururo.2012.03.031

Cited by 73 publications

(67 citation statements)

References 31 publications

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“…A total of 24 8–9 week-old female C57BL/6N mice (Envigo, Frederick, MD) weighing 18–20 g were used, and SCI mice underwent complete transection of Th8/9 spinal cord after induction of anesthesia by intraperitoneal (i.p.) injection of pentobarbital (50 mg/kg), according to the methods described previously (McCarthy et al, 2009; Ikeda et al, 2012; Kadekawa et al, 2016). SCI animals were treated with ampicillin (100 mg/kg, subcutaneously) for 5 days post-SCI and this treatment was continued twice a week afterwards.…”

Section: Methodsmentioning

confidence: 99%

Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury

et al. 2017

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Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRG) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. The number of CMV promoter vector-labeled neurons was not altered after SCI. The number of CGRP and TRPV1 promoter vector-labeled neurons was significantly increased whereas the number of NF200 vector-labeled neurons was decreased in L6 DRG after SCI. The median size of CGRP promoter-labeled C-fiber neurons was increased from 247.0 in SI mice to 271.3 µm2 in SCI mice whereas the median cell size of TRPV1 promoter vector-labeled neurons was decreased from 245.2 in SI mice to 216.5 µm2 in SCI mice. CGRP and TRPV1 mRNA levels of laser-captured bladder afferent neurons labeled with Fast Blue were significantly increased in SCI mice compared to SI mice. Thus, using a novel HSV vector-mediated neuronal labeling technique, we found that SCI induces expansion of the CGRP- and TRPV1-expressing C-fiber cell population, which could contribute to C-fiber afferent hyperexcitability and NDO after SCI.

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Section: Methodsmentioning

confidence: 99%

Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury

et al. 2017

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“…This phenomenon could be explained by the mechanism of onabotulinumtoxinA. Data from studies in experimental animals [25,26] suggest that onabotulinumtoxinA blocks release of different neuropeptides and neurotransmitters into the neuromuscular junction, and acts on both motor and sensory pathways [27]. Therefore, onabotulinumtoxinA may be more effective in preventing activation of muscarinic receptors compared with antimuscarinic drugs [28].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Adverse Events Associated With Use of OnabotulinumtoxinA for Treatment of Neurogenic Detrusor Overactivity: A Meta-Analysis

Yuan

Cui

et al. 2017

Int Neurourol J

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PurposeOnabotulinumtoxinA is used widely for the treatment of neurogenic detrusor overactivity. We conducted a systematic review and meta-analysis to assess its efficacy and safety for neurogenic detrusor overactivity treatment.MethodsA systematic literature review was performed to identify all published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for neurogenic detrusor overactivity treatment. MEDLINE, Embase, and the CENTRAL were employed. Reference lists of retrieved studies were reviewed carefully.ResultsSix publications involving 871 patients, which compared onabotulinumtoxinA with a placebo were analyzed. Efficacy of onabotulinumtoxinA treatment was shown as a reduction of the mean number of urinary incontinence episodes per day (mean difference, -1.41; 95% confidence interval [CI], -1.70 to -1.12; P<0.00001), maximum cystometric capacity (135.48; 95% CI, 118.22–152.75; P<0.00001), and maximum detrusor pressure (-32.98; 95% CI, -37.33 to -28.62; P<0.00001). Assessment of adverse events revealed that complications due to onabotulinumtoxinA injection were localized primarily to the urinary tract.ConclusionsThis meta-analysis suggests that onabotulinumtoxinA is an effective treatment for neurogenic detrusor overactivity with localized advent events.

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“…The combination of these mechanisms leads to a long-term inhibition of afferent and efferent neural transmission, which is used in the treatment of NDO. This influence on the afferent neural pathway is most likely responsible for the long-term effect of BoNT/A [4]. …”

Section: Introductionmentioning

confidence: 99%

Submucosal Administration of OnabotulinumtoxinA in the Treatment of Neurogenic Detrusor Overactivity: Pilot Single-Centre Experience and Comparison with Standard Injection into the Detrusor

Šámal¹,

Mečl²,

Šrám

2013

Urol Int

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Introduction: Apart from the standard intramural administration of botulinum neurotoxin A (BoNT/A) to the detrusor, intense research is taking place into new means of administration in view of the complex mechanism of action of BoNT/A. Methods: An open, randomised, prospective study was performed on a total of 23 patients with neurogenic detrusor overactivity. Following randomisation, patients were treated with 300 U of onabotulinumtoxinA (onaBoNT/A) in either the submucosa or the detrusor. Urodynamic examinations were carried out, and a bladder diary was kept both prior to and 12 weeks after the treatment. All patients stopped taking anticholinergics 1 week prior to the treatment. Results: In both the submucosa and detrusor groups, we recorded a significant improvement in the monitored urodynamic parameters and significant decreases in the frequency of urinary incontinence episodes following the treatment. A comparison of the two groups showed no significant difference between the two forms of application, with the exception of voided volume (p = 0.007). Conclusion: A comparison of the two administration methods did not show any significant difference between onaBoNT/A administration to the submucosa and to the detrusor. Thus, the submucosal injection of onaBoNT/A represents an equally effective approach for its administration to patients.

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Botulinum Neurotoxin Serotype A Suppresses Neurotransmitter Release from Afferent as Well as Efferent Nerves in the Urinary Bladder

Cited by 73 publications

References 31 publications

Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury

Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury

Efficacy and Adverse Events Associated With Use of OnabotulinumtoxinA for Treatment of Neurogenic Detrusor Overactivity: A Meta-Analysis

Submucosal Administration of OnabotulinumtoxinA in the Treatment of Neurogenic Detrusor Overactivity: Pilot Single-Centre Experience and Comparison with Standard Injection into the Detrusor

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