Innervation of the Epithelium and Lamina Propria of the Urethra of the Female Rat

Abstract

The aim of this study was to characterize the number, type and distribution of immunochemically identified nerves in epithelium and lamina propria of the female rat urethra. Urethras from female Sprague-Dawley rats (n = 12) were fixed, frozen and sectioned (8 μm). Standard immunohistochemical techniques were used to identify putative nerves using the following antibodies: calcitonin gene related peptide (cgrp), neuronal nitric oxide synthase (nNos), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (vacht). The number, distribution and characteristics of all immunoreactive (IR) structures adjacent to the urethral epithelium and in the lamina propria was assessed. In the bladder, few cgrp-IR and vacht-IR fibers were associated with the urothelium or suburothelium of the lateral wall. In contrast, large numbers of vacht-IR, nNos-IR and cgrp-IR fibers were found close to the epithelium and subepithelium of the bladder neck and throughout the urethra. The number of cgrp-IR fibers was significantly higher in the urethra in comparison with the bladder neck. A population of undescribed cgrp-IR cells associated with the bladder neck and proximal urethra has been characterized. Each of these cells appears to be associated with a nerve fiber. In the distal urethra, the number of peptidergic fibers penetrating the epithelium was significantly higher than the rest of the urethra. Clearly, this study has revealed a highly complex and heterogeneous network of putative afferent nerves fibers along the length of the urethra. These structural specializations need to be taken into account when probing the different functions of the urethra. Anat Rec, 302:201-214, 2019. © 2019 players.brightcove.net/656326989001/default_default/index.html? videoId=5988401873001 BB = bladder base; BN = bladder neck; det = detrusor; DU = distal urethra; epi = epithelium; F = epithelial folds; lp = lamina propria; lum = lumen; LW = bladder lateral wall; MU = mid urethra; PU = proximal urethra; sm = smooth muscle; ss = striated muscle sphincter

The urethra in continence and sensation: Neural aspects of urethral function

“…21 Autonomic fibers are also present ( Figure 2B,C, 2B1, B2 and 2C1, C2), as a recent study documented the presence of large numbers of sympathetic and parasympathetic tracts close to the epithelium and in the lamina propria of the bladder neck and throughout the urethra of the female rat. 21 While the fine mechanisms underlying how urethragenerated sensory input is perceived and conveyed by afferents are still unclear, there is evidence supporting that urethral sensation may be at least partially dependent on specialized urothelial cells. These cells show "neuron-like" properties, including the ability of sense and respond to chemical and mechanical stimuli, which allows them to communicate with nerves and myofibroblasts in the lamina propria.…”

“…Importantly, at least in rodents, the innervation patterns, particularly of sensory innervation, seem to differ according to urethral zone, 20 as well in as between the anterior and posterior regions. 21 Autonomic fibers are also present (Figure 2B,C, 2B1, B2 and 2C1, C2), as a recent study documented the presence of large numbers of sympathetic and parasympathetic tracts close to the epithelium and in the lamina propria of the bladder neck and throughout the urethra of the female rat. 21 While the fine mechanisms underlying how urethragenerated sensory input is perceived and conveyed by afferents are still unclear, there is evidence supporting that urethral sensation may be at least partially dependent on specialized urothelial cells.…”

“…In the rat spinal cord, sensory input generated in the urethra is conveyed to L6‐S2 spinal segments 3 (Figure 3). Importantly, at least in rodents, the innervation patterns, particularly of sensory innervation, seem to differ according to urethral zone, 20 as well in as between the anterior and posterior regions 21 . Autonomic fibers are also present (Figure 2B,C, 2B1, B2 and 2C1, C2), as a recent study documented the presence of large numbers of sympathetic and parasympathetic tracts close to the epithelium and in the lamina propria of the bladder neck and throughout the urethra of the female rat 21 …”

Mapping afferent and pelvic postganglionic neurons of the urethra from female rats: The L6 DRG is the major primary afferent supplier

“…Previous studies suggest that sensoryDRG neurons projecting to the urethra may innervate epithelium, lamina propria, muscle layers, and adventitia 13,19 . Moreover, sensory fibers of the proximal urethra are linked to distension 13 .…”

“…11 Previous studies suggest that sensoryDRG neurons projecting to the urethra may innervate epithelium, lamina propria, muscle layers, and adventitia. 13,19 Moreover, sensory fibers of the proximal urethra are linked to distension. 13 Fibers penetrating the epithelium might be sensitive to lateral movements of the epithelium, 20 such as the displacements that might occur during urine flow.…”