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Peptidergic nerve fibers in the urethra: Morphological and neurochemical characteristics in female mice of reproductive age
Author(s) -
Barry Christine M.,
Ji Esther,
Sharma Harman,
Yap Pauline,
Spencer Nicholas J.,
Matusica Dusan,
Haberberger Rainer V.
Publication year - 2018
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.23434
Subject(s) - urethra , anatomy , calcitonin gene related peptide , medicine , terminal nerve , vasoactive intestinal peptide , pudendal nerve , free nerve ending , retrograde tracing , nerve fiber , lumbosacral joint , neuropeptide , pathology , immunohistochemistry , receptor , hormone
Background Peptidergic nerve fibers provide important contributions to urethral function. Urethral innervation of female mice is not well documented. Aims To determine the distribution and projection sites of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene‐related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the urethra of wild‐type control mice and compare innervation characteristics between the proximal and distal urethra of young nullipara and older multipara mice. Furthermore, to identify the location and neurochemical coding of the spinal afferent nerve endings in the urethra, whose sensory neurons reside in lumbosacral dorsal root ganglia (DRG). Methods Multiple labeling immunohistochemistry of urethral sections of nulliparous (6‐8 weeks old), and multiparous (9‐12 months old) mice, and anterograde axonal tracing from L5‐S2 (DRG) in vivo. Results Abundant VIP‐, CGRP‐, SP‐, and NPY‐immunoreactive nerve fibers were identified in the adventitia, muscularis, and lamina propria of proximal and distal segments of the urethra. A proportion of fibers were closely associated with blood vessels, glands, and cells immunoreactive for PGP9.5. The epithelium contained abundant nerve fibers immunoreactive for CGRP and/or SP. Epithelial innervation was increased in the distal urethra of multipara mice. Abundant fibers were traced from L5‐S2 DRG to all urethral regions. Conclusions 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.