Functional segregation within the pelvic nerve of male rats: a meso- and microscopic analysis.

Martin M Bertrand,Peregrine B Osborne,Janet R Keast,Nadja Korajkic

doi:10.1111/joa.13221

Abstract

The pelvic splanchnic nerves are essential for pelvic organ function and have been proposed as targets for neuromodulation. We have focused on the rodent homologue of these nerves, the pelvic nerves. Our goal was to define within the pelvic nerve the projections of organ‐specific sensory axons labelled by microinjection of neural tracer (cholera toxin, subunit B) into the bladder, urethra or rectum. We also examined the location of peptidergic sensory axons within the pelvic nerves to determine whether they aggregated separately from sacral preganglionic and paravertebral sympathetic postganglionic axons travelling in the same nerve. To address these aims, microscopy was performed on the major pelvic ganglion (MPG) with attached pelvic nerves, microdissected from young adult male Sprague–Dawley rats (6–8 weeks old) and processed as whole mounts for fluorescence immunohistochemistry. The pelvic nerves were typically composed of five discrete fascicles. Each fascicle contained peptidergic sensory, cholinergic preganglionic and noradrenergic postganglionic axons. Sensory axons innervating the lower urinary tract (LUT) consistently projected in specific fascicles within the pelvic nerves, whereas sensory axons innervating the rectum projected in a complementary group of fascicles. These discrete aggregations of organ‐specific sensory projections could be followed along the full length of the pelvic nerves. From the junction of the pelvic nerve with the MPG, sensory axons immunoreactive for calcitonin gene‐related peptide (CGRP) showed several distinct patterns of projection: some projected directly to the cavernous nerve, others projected directly across the surface of the MPG to the accessory nerves and a third class entered the MPG, encircling specific cholinergic neurons projecting to the LUT. A subpopulation of preganglionic inputs to noradrenergic MPG neurons also showed CGRP immunoreactivity. Together, these studies reveal new molecular and structural features of the pelvic nerves and suggest functional targets of sensory nerves in the MPG. These anatomical data will facilitate the design of experimental bioengineering strategies to specifically modulate each axon class.

Highlights

In recent years, many new clinical applications have emerged for bioelectronics and neuromodulation to regulate organ function (Birmingham et al 2014; Horn et al 2019; Moore et al 2019; Payne et al 2019)
Several fundamental anatomical and functional principles of this sacral neuroregulatory system mirror the vagus, with the functionally homologous nerves being the pelvic splanchnic nerves and pelvic nerve. These multi-functional nerves contain axons of all parasympathetic preganglionic neurons that regulate pelvic organ function, synapsing on autonomic ganglion neurons that project to relevant tissues in the urinary or digestive tracts, or sex organs. These final motor neurons lie in a complex structure, the inferior hypogastric plexus, whereas in rodents they are aggregated in the major pelvic ganglia (MPGs)
To investigate the trajectory of sensory axons projecting in the pelvic nerve, we closely followed tracts of calcitonin gene-related peptide (CGRP)-positive axons from their point of entry to the major pelvic ganglion (MPG), co-staining selected ganglia for tyrosine hydroxylase (TH) or CTB

Summary

| Introduction

Many new clinical applications have emerged for bioelectronics and neuromodulation (electrical modulation of neural properties) to regulate organ function (Birmingham et al 2014; Horn et al 2019; Moore et al 2019; Payne et al 2019). The most common clinical approach for sacral neuromodulation is to place an electrode in front of the left or right third sacral foramen (Matzel et al 2017), providing the capacity to influence activity in two major neural projections, the pudendal (somatic) and pelvic splanchnic (visceral) nerves, that usually originate from the second to third sacral roots (Baader and Herrmann, 2003) This approach, has the potential to modulate a diverse range of tissues, including the striated muscle of sphincters and pelvic floor, and smooth muscle, epithelia and glandular tissues of the urogenital organs and lower bowel. We extend understanding of this potentially important site of crosstalk between sensory and autonomic systems by examining the projections and associations of axons immunoreactive for calcitonin gene-related peptide (CGRP) in full-thickness MPG with attached nerves

| Materials and methods

| Results

Findings

| Discussion