Response Properties of Urethral Distension Evoked Unifiber Afferent Potentials in the Lower Urinary Tract.

PURPOSE: It is well known that afferent input from the urethra can modulate bladder function. Nevertheless, little is known about the functional properties of urethral afferents. In the current study we investigated the effect of urethral distension on single fiber afferent activities of the lower urinary tract in the female rat. MATERIALS AND METHODS: Female Sprague Dawley® rats were anesthetized. Single fiber afferent activities were recorded from the left L6 dorsal root and classified by conduction velocity. The response of pelvic and pudendal units on urethral distension (60 seconds) was measured. Two distension diameters were measured in the proximal and the distal urethra. RESULTS: A total of 93 pelvic and 72 pudendal units were isolated in 15 rats. Of the units 20 (8 pelvic and 12 pudendal) were responsive to urethral distension. Three patterns of response could be distinguished, including a fast adapting and 2 groups of slow adapting afferents. The largest grade of distension resulted in the greatest response in both nerves. Five pelvic and 3 pudendal units responded exclusively to proximal distension, 2 pelvic and 5 pudendal units responded to distal distension, and 1 pelvic and 4 pudendal units responded to both types of distension. The responses were reproducible. No association was found between the type of nerve and the location of the response to distension. CONCLUSIONS: This electrophysiological study demonstrates the presence of urethral distension evoked afferents in the pelvic and pudendal nerves, and describes their response to distension. Differences in sensory signaling in type and in location were demonstrated. The current technique can be used for further investigation of urethral afferents.

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

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. © 2018 Wiley Periodicals, Inc.

Regional Structural and Functional Specializations in the Urethra of the Female Rat: Evidence for Complex Physiological Control Systems.

This study characterizes the complex structural and functional elements of the female rat urethra that may be involved in controlling urethral closure and continence. Urethras were dissected from female Sprague-Dawley rats (N = 12) euthanized by pentobarbital overdose. Tissues were fixed (4% paraformaldehyde), frozen, and sectioned (8 µm) for light microscopy and immunohistochemistry. Antibodies were used to detect immunoreactivity to calcitonin gene related peptide, nitric oxide synthase, vesicular acetylcholine transporter, and tyrosine hydroxylase. Measurements of urethral wall compliance were taken along its length and in different axes using a closed ended catheter with a circular aperture. The bladder neck and proximal urethra are characterized by a highly folded epithelium and lamina propria. A smooth muscle layer is apparent but not pronounced. Distal to this region the smooth muscle layer thickens and forms the body of the internal sphincter, which has a complex innervation. In the mid urethra, the smooth muscle is thickened resulting in a luminal protrusion, producing an occlusion of the lumen. The structure of the distal urethra is different. The epithelium has few folds and, immediately below the lamina propria large thin walled vascular lacunae can be found. Measurements of the urethral wall compliance demonstrate distinct regional differences with proximal and distal specialisations. These variations, which correlate with muscular and vascular elements, suggest the operation of discrete systems, hence effecting urethral closure during filling. An understanding of these systems may yield insights into urethral pathology and direct approaches to develop pharmacological interventions to promote continence. Anat Rec, 301:1276-1289, 2018. © 2018 Wiley Periodicals, Inc.