Expression of Low Affinity Nerve Growth Factor Receptor p75 in Classic Bladder Exstrophy.

Martin Promm,Wolfgang H Roesch,Stefanie Götz,Winfried Neuhuber,Wolfgang Otto,Maximilian Burger,Peter Rubenwolf,Karolina Müller,Florian Weber

doi:10.3389/fped.2021.634343

Abstract

Successful primary closure of classic bladder exstrophy (BE) is crucial for development of bladder capacity and voided continence. It is universally agreed that an intensive pain management including the use of caudal epidural anesthesia is an essential cornerstone for the outcome of this complex surgery. Whether and to what extent pain is caused by structural or functional changes is not yet known. The nerve growth factor (NGF) is regarded as a marker for pain in different bladder disorders. This prospective study investigated the role of histological alterations and NGF in patients with BE including 34 patients with BE and 6 patients with congenital vesicoureterorenal reflux (VUR) who served as controls. Between January 2015 and April 2020 transmural bladder biopsies were taken from the posterior bladder wall during delayed primary bladder closure. The samples were stained for histological evaluation and subjected to immunohistochemistry to analyze NGFR p75. Differences in histological alterations were examined with Fisher's exact test, and Mann-Whitney-U-test was used to compare the NGFR p75 staining intensity between patients with BE and controls. Patients with BE showed significantly more often acute inflammation (p < 0.001), squamous metaplasia (p = 0.002), and cystitis glandularis (p = 0.005) as well as NGFR p75 in the urothelium (p = 0.003) than patients with VUR. A limitation of this study is the small number of participants due to the rare disease entity. Similar to other painful bladder disorders, pain transmission in BE after intitial closure may in part be facilitated by elevated NGF signaling through its receptor.

Highlights

Successful primary closure is crucial for the development of bladder capacity and voided continence [1, 2]
In this study we looked on the occurrence of NGFR p75 and histological alterations in 34 patients with bladder exstrophy (BE) presenting for delayed primary closure and six patients with vesicoureterorenal reflux (VUR) who served as controls
Our results showed a statistically significant difference in NGFR p75 in the urothelium between patients with BE and patients with VUR

Summary

Introduction

Successful primary closure is crucial for the development of bladder capacity and voided continence [1, 2]. In a majority of unclosed bladders urothelial differentiation changes could be shown [6]. These findings may result in a dysfunctional barrier of the urothelium with implications for the structural and functional properties of the unclosed bladder wall. NGF is produced by the bladder smooth muscle and the urothelium [13]. NGF is assumed to mostly affect afferent fibers. NGF seems to play a significant role in abnormal afferent signaling and in increased bladder sensations [12, 13]. Whether and to what extent peri- and postoperative pain might be caused by structural or functional changes in the exstrophic bladder wall is yet unknown

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Conclusion