Peptidergic nerve fibers in the urethra: Morphological and neurochemical characteristics in female mice of reproductive age

Abstract

We present the first identification of spinal afferent endings in the urethra. Peptidergic nerve fibers, including multiple populations of spinal afferents, provide rich innervation of the female mouse urethra. The morphology of fibers in the epithelium and other regions suggests multiple nerve-cell interactions impacting on urethral function.

Evidence for an urethro‐vesical crosstalk mediated by serotonin

“…Patients with stress urinary incontinence may report the sensation of imminent voiding and show involuntary detrusor contractions during cystometry immediately after urine leak induced by increased abdominal pressure. Further supporting an urethro‐vesical crosstalk, afferent urethral input is conveyed through pudendal and pelvic nerves to lumbosacral spinal regions that also receive sensory information from the bladder …”

“…3,10 The mechanism of urethral sensory fiber excitation is unknown. It may occur through a direct contact between the urine flow and free sensory fiber endings emerging on the surface of the urethral epithelium 8,11 or indirectly through signaling molecules released specialized epithelial cell into the sub-epithelium.…”

“…Populations of specialized cells have been identified in the urethral epithelium of several mammalian species, 8,[12][13][14][15] including humans. 16,17 Electron microscopy studies identified cells with apical microvilli and basal secretory granules expressing acetylcholine (ACh) and serotonin (5-HT).…”

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

“…Next to a dense peptidergic subepithelial plexus, we also identified a high number of penetrating peptidergic fibers in the urethral epithelium, with a significant increase toward the distal urethra. A recent study in mice also identified innervation differences in the epithelial layer of the urethra (Barry et al, ). Here the studied fibers showed immunoreactivity for the pan‐neuronal marker PGP9.5, with an increased amount of epithelial fibers in the distal urethra of multiparous mice.…”

“…The overall innervation of the epithelium and subepithelium of the proximal urethra has been addressed in the rat by Grol et al (). The distribution of peptidergic nerve fibers throughout the urethra has been described in whole mount urethral preparations of the dog (Tamaki et al, ; Iwanaga et al, ) and recently in urethral sections in the mouse (Barry et al, ).…”