A three dimensional nerve map of human bladder trigone

Purves, J. Todd; Spruill, Laura; Borisko, Elyse; McCants, Alden; Mugo, Elizabeth; Wingard, Ainsley; Trusk, Thomas C.; Bacro, Thierry; Hughes, Francis M.

doi:10.1002/nau.23049

Cited by 16 publications

(8 citation statements)

References 12 publications

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“…It has been established that onabotulinumtoxinA inhibits overactivity of the detrusor 22 . In addition, our understanding of the mechanism of onabotulinumtoxinA action has continued to evolve over time, with studies demonstrating suburothelial sensory innervation changes following onabotulinumtoxinA injections into the bladder, 21 leading to the hypothesis that there may be benefit to targeting the trigone area because of the rich sensory innervation 23 . Studies using fewer injections than in the standard 20‐injection‐site paradigm have not demonstrated any major differences in outcomes, 24–27 and evidence for the theoretical risk of urine reflux when onabotulinumtoxinA is injected into the trigone has not materialized 15–17 …”

Section: Discussionmentioning

confidence: 99%

“…22 In addition, our understanding of the mechanism of onabotulinumtoxinA action has continued to evolve over time, with studies demonstrating suburothelial sensory innervation changes following onabotulinumtox-inA injections into the bladder, 21 leading to the hypothesis that there may be benefit to targeting the trigone area because of the rich sensory innervation. 23 Studies using fewer injections than in the standard 20injection-site paradigm have not demonstrated any major differences in outcomes, [24][25][26][27] and evidence for the theoretical risk of urine reflux when onabotulinumtox-inA is injected into the trigone has not materialized. [15][16][17] The LO-BOT study assessed the efficacy and safety of an unapproved alternative injection paradigm using a lower total injection volume of onabotulinumtoxinA and fewer injections that were focused on the lower bladder, including the trigone, to help maintain upper bladder function and potentially reduce the need for CIC.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder

MacDiarmid,

Glazier,

McCrery

et al. 2023

Neurourology and Urodynamics

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AimsIn studies utilizing a 20‐injection‐site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10‐injection‐site paradigm targeting the lower bladder.MethodsIn this phase 4, double‐blind, parallel‐group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI‐free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder.ResultsOf 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double‐blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (−2.9) versus placebo (−0.3) (least squares mean difference [LSMD]: −2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75–50.37]), ≥75% (OR: 7.25 [2.00–26.29]), and ≥50% improvement (OR: 4.79 [1.87–12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: −2.24, p < 0.0001), nocturia (LSMD: −0.71, p = 0.0004), and urgency (LSMD: −2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23–52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double‐blind period; no females used CIC during the double‐blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo.ConclusionIn patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder

MacDiarmid,

Glazier,

McCrery

et al. 2023

Neurourology and Urodynamics

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“…New research indicates that the trigone was most densely innervated in the bladder. These nerves respond to passive distension and active contraction of the bladder and are the sensory component during a normal micturition cycle (33). Botulinum toxins have a direct role in the sensory nerve endings as well as the synaptic nerve junctions.…”

Section: Discussionmentioning

confidence: 99%

Trigonal-Sparing vs. Trigonal-Involved OnabotulinumtoxinA Injection for the Treatment of Overactive Bladder: A Systematic Review and Meta-Analysis

et al. 2021

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Objective: Overactive bladder (OAB) is a disease characterized by the presence of urinary urgency. We carried out a meta-analysis to assess the effectiveness and safety of trigonal-involved injection of onabotulinumtoxinA (BoNT-A) in comparison with the trigonal-sparing technique in cases with OAB [neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO)].Methods: Randomized controlled trials (RCTs) of BoNT-A injection for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The datum was calculated by RevMan version 5.3.0. The original references of relating articles were also reviewed.Results: In total, six RCTs involving 437 patients were included in our analysis. For OAB, the trigone-including group showed a different patient symptom score (p = 0.03), complete dryness rate (p = 0.002), frequency of incontinence episodes (p = 0.01), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.0004) compared with the trigone-sparing group. Also, a trigone-including intradetrusor injection demonstrated a significant improvement in the patient symptom score (p = 0.0004), complete dryness rate (p = 0.0002), frequency of incontinence episodes (p = 0.0003), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.00006) compared with the trigone-sparing group for treatment of NDO. The adverse events rates were similar in both groups.Conclusions: The meta-analysis has demonstrated that trigone-including BoNT-A injection was more effective compared with the trigone-sparing injection for the treatment of OAB, especially for NDO.

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“…Although previous studies demonstrated urinary bladder innervation or suburothelial microvascular structure in human or rodents at 3D level [16][17][18][19], anatomic information about neurovascular network in whole layers of urinary bladder are still lacking. In the present study, therefore, we present an immunohistochemical staining method that delineates 3D neurovascular systems of mouse urinary bladder at a high resolution.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Reconstruction of Neurovascular Network in Whole Mount Preparations and Thick-Cut Transverse Sections of Mouse Urinary Bladder

Minh

Song

Choi

et al. 2021

World J Mens Health

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Purpose: Proper functional and structural integrity of nervous and vascular system in urinary bladder plays an important role in normal bladder function and the disruption of these structures is known to be related to lower urinary tract symptoms. Here, we present an immunohistochemical staining method that delineates neurovascular structures in the mouse urinary bladder by using immunohistochemical staining with three-dimensional reconstruction. Materials and Methods: The urinary bladder was harvested from 8-week-old C57BL/6 male mouse. Lamina propria and detrusor muscle layer were dissected for whole mount staining, and thick-cut (60-μm) sections were prepared for full-thickness bladder staining. Immunofluorescent staining of bladder tissue was performed with antibodies against CD31 (an endothelial cell marker), smooth muscle α-actin (a smooth muscle cell marker), NG2 (a pericyte marker), and βIII-tubulin (a neuronal marker). We reconstructed three-dimensional images of bladder neurovascular system from stacks of two-dimensional images. Results: Three-dimensional images obtained from thick-cut sections clearly provided good anatomic information about neurovascular structures in the three layers of bladder, such as urothelium, lamina propria, and detrusor muscle layer. Whole mount images of lamina propria and detrusor muscle layer also clearly delineated spatial relationship between nervous and vascular systems. The microvessel density was higher in the lamina propria than in the detrusor muscle layer. Nerve fibers were evenly innervated into the lamina propria and detrusor muscle. Conclusions: This study provides comprehensive insight into three-dimensional neurovascular structures of mouse urinary bladder. Our technique may constitute a standard tool to evaluate pathologic changes in a variety of urinary bladder diseases.

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A three dimensional nerve map of human bladder trigone

Cited by 16 publications

References 12 publications

Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder

Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder

Trigonal-Sparing vs. Trigonal-Involved OnabotulinumtoxinA Injection for the Treatment of Overactive Bladder: A Systematic Review and Meta-Analysis

Three-Dimensional Reconstruction of Neurovascular Network in Whole Mount Preparations and Thick-Cut Transverse Sections of Mouse Urinary Bladder

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