Local differences in vagal afferent innervation of the rat esophagus are reflected by neurochemical differences at the level of the sensory ganglia and by different brainstem projections

Abstract

The objective of the present study was to characterize further the vagal afferent fibers in the rat esophagus, particularly those in its uppermost part, their cell bodies in vagal sensory ganglia, and their central projections. We applied immunohistochemistry for calretinin, calbindin, and calcitonin gene-related peptide (CGRP); retrograde tracing with FluoroGold; and transganglionic tracing with wheat germ agglutinin-horseradish peroxidase in combination with neurectomies. Vagal terminal structures in the muscularis propria of the whole esophagus consisted of calretinin-immunoreactive intraganglionic laminar endings that were linked to cervical vagal and recurrent laryngeal nerve pathways. The mucosa of the uppermost esophagus was innervated by a very dense net of longitudinally arranged, calretinin-positive fibers that were depleted by section of the superior laryngeal nerve. Distal to this area, the mucosa was virtually devoid of calretinin-immunoreactive vagal afferents. Calretinin-positive mucosal fibers in the upper cervical esophagus were classified into four types. One type, the finger-like endings, was sometimes immunoreactive also for CGRP. About one-third of cell bodies in vagal sensory ganglia retrogradely labeled from the upper cervical esophagus expressed CGRP, whereas two-thirds coexpressed calretinin and calbindin but not CGRP. In addition to the central subnucleus of the nucleus of the solitary tract, vagal afferents from the upper cervical esophagus also projected heavily to the interstitial subnucleus. This additional projection was attributed to mucosal afferents traveling through the superior laryngeal nerve. The present study provides a possible morphological basis for bronchopulmonary and aversive reflexes elicited upon stimulation of the esophagus.

Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation

“…The presence of esophageal mucosal afferents is well documented in animals (17,26), and evidence exists for presence of sensory nerve fibers in human esophageal mucosa (13). Our findings indicate that mucosal mechanoreceptors are of primary importance in mediating the esophago-UES relaxation response, whereas deep mechanoreceptors primarily mediate UES contractile responses.…”

“…A study of receptive fields of vagal afferent fibers in a guinea pig esophagus suggests that the IGLEs are tension-sensitive receptors (28). Various types of nerve endings have also been demonstrated within the esophageal mucosa (26) although it is unknown whether these correspond to the receptive fields of vagal afferent fibers.…”

ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa

“…In the esophagus, ATP released from esophageal keratinocytes may act in different ways on nerve endings that innervate the esophagus. ATP may reach and activate purinergic receptors expressed in intraganglionic laminar endings (23,37,45), since they are in intestine (3). Alternatively, vagal and spinal mucosal afferents may detect released ATP because they abut on and penetrate the esophageal epithelium with small branches (17,30,45).…”

Key Role of Mucosal Primary Afferents in Mediating the Inhibitory Influence of Capsaicin on Vagally Mediated Contractions in the Mouse Esophagus

“…The mucosa of the alimentary tract, in addition to its absorptive and secretive functions, serves as a sensory organ that perceives different sensory modalities and transducts them to the enteric as well as the central nervous systems. Vagal innervation of the mucosa shows the greatest density in the upper cervical esophagus which steeply decreases in the lower cervical and thoracic esophagus [10,20,32]. On the other hand, spinal afferents are distributed rather evenly from oral to aboral [10].…”