SPARC: Abundance, Chemical Content and Regional Distributions of Nerve Fibers in the Human Gastric Muscle and Mucosa

Disorders of gastric motility and sensation, including gastroparesis, are common, debilitating and currently poorly treated. To develop new treatments for these disorders, a thorough understanding of the gastric innervation and its pathology in humans is required. We have developed methods to identify and quantify the density of different classes of nerve fibers to the gastric muscle and mucosa. To do this we employed immunohistochemistry using characterized antibodies and a grid‐based quantitation method combined with high resolution confocal microscopy in resection tissue and biopsies from the gastric fundus and corpus. In the muscle we have identified nerve fibers immunoreactive for a range of neurochemical markers including neuronal nitric oxide synthase (NOS), vasoactive inhibitory peptide (VIP), tachykinins (TK), gastrin releasing peptide (GRP), neuropeptide Y (NPY), vesicular acetylcholine transporter (VAChT) and tyrosine hydroxylase (TH). Neuronal NOS and VIP were commonly colocalized in putative inhibitory nerves innervating the external musculature. We saw extensive labelling for VAChT and TK, both markers of the excitatory fibers innervating the muscle. GRP and NPY were also present in subgroups of excitatory nerve fibers. The density of inhibitory fibers (NOS) was greater than excitatory fibers (TK) in all external muscle layers. TH was found in a proportion of fibers in the muscle, suggesting direct sympathetic innervation of the muscle occurs in human stomach. These TH fibers also contained NPY but were separate from NPY immunoreactive excitatory muscle motor nerves.Prominent in mucosal innervation were fibers immunoreactive for VIP and GRP and a separate population containing VAChT. Another population of fibers containing NPY and TH were found around mucosal glands and also around arteries supplying the mucosa. For all common fiber types in the mucosa there was a gradient of densities such that most fibers were found in the bottom third of the mucosa and few fibers were found in the top third of the glands near the lumen. Rare CGRP containing fibers were also seen in the mucosa but were not present in every section suggesting they are rare and unevenly distributed.We conclude that the signature chemistries of nerve fibers that innervate the gastric muscle and mucosa in human are similar to those present in other species, including rat. An exception is the prominent direct innervation of the gastric muscle by extrinsic sympathetic axons which is often absent in small mammals. This parallel chemistry will allow us to extrapolate circuits determined experimentally in rat to human and to identify cell body types in the myenteric ganglia.Support or Funding InformationThis work was supported by NIH (SPARC) grant ID # OT2OD023847 (PI Terry Powley) to John Furness and Martin Stebbing.