id="ulink_8180b9bc-c479-57c7-9cfa-de811689fcd2">Figure 5.8 Muscular architecture of the pharynx and upper esophagus from the laterodorsal aspect. The cricopharyngeus muscle has an upper portion that is continuous with the inferior constrictor muscle and a lower portion that encircles the region at the approximate location of the highest upper esophageal sphincter pressure. Between the two portions is a small space, the Killian triangle, where a Zenker’s diverticulum will occur. The lower border of the cricopharyngeus and the origins of the longitudinal layer of the upper esophageal striated muscle form another triangle, Laimer’s triangle.
Source: Liebermann‐Meffert [80] with permissions of Oxford University Press.
Pharyngeal stimulation with small volumes of water, 0.1–1.5 cm, will induce the oropharyngeal stage of swallowing with UES relaxation. However, prior to initiation of the swallow, UES pressure increases [13].
Esophageal stage motor activity
Esophageal body
Anatomy, structure, and innervation
The esophagus is a 20–22 cm long muscular tube with sphincters at either end. Measured manometrically, the total length can vary between 17 and 30 cm with a mean of 23 cm [121]. The proximal 5%, including the UES, is composed of striated muscle. Transition from striated to smooth muscle occurs progressively in the middle 35–40%, and the distal 50–60% is composed entirely of smooth muscle [122]. This transition occurs more proximally in the inner circular muscle layer. The outer longitudinal muscle originates anteriorly from the cricoid cartilage along with some fibers from the cricopharyngeus muscle. As the esophagus passes distally and posteriorly, there is a triangle at the top end that is free of this longitudinal layer, called Laimer’s triangle (see Figure 5.8). The longitudinal layer is present through the remainder of the esophageal body to the level of the LES, changing from striated to smooth muscle more distally compared to the circular muscle. There is no serosa covering the esophagus, with only a thin layer of connective tissue allowing the esophagus to move more freely within the mediastinum.
There is a myenteric plexus of ganglion cells and nerve fibers in both smooth and striated muscle sections between the circular and longitudinal muscle layers (Auerbach’s plexus), more prominent in the smooth muscle section, which in turn release neurotransmitters to the esophageal smooth muscle. Additionally, there is a submucosal plexus (Meissner’s plexus), which is sparse compared to the myenteric plexus [123]. In the smooth muscle portion, ganglion cells in the myenteric plexus receive efferent vagal preganglionic motor fibers from the DMNV, which provide excitatory and inhibitory innervation to the muscle layers. Thus, pre‐ and postganglionic motor neurons can be excitatory or inhibitory [124]. The excitatory pathway arises from the rostral part of the DMN, whereas the inhibitory pathway arises from the caudal part. Activation of inhibitory nerves occurs simultaneously in the entire esophagus at the onset of swallowing (deglutitive inhibition), followed by activation of excitatory neurons resulting in peristaltic contraction [125, 126]. Through their connectivity within the enteric nervous system, these ganglia provide a local neural mechanism for peristalsis and distal inhibition. Sympathetic motor input is directed primarily to the myenteric plexus from intermediolateral columns of thoracic spine through sympathetic ganglia, which are denser in the smooth muscle esophagus compared to the striated muscle [127, 128].
Esophageal vagal afferent nerve endings are found in the mucosa, the muscularis propria (intramuscular array endings, IMAs), and the intraganglionic laminar endings (IGLEs). Vagal sensory information is transmitted centrally by nerves with their cell bodies in the nodose ganglia in the neck and is responsible for the sensory–motor regulation of the SPG for peristalsis and for esophagus‐initiated reflexes [129]. Sensory receptors include IGLEs [130] and potentially interstitial cells of Cajal (ICCs) [131] and IMAs [132, 133]. IGLEs are a specialized laminar structure that cover myenteric ganglia in the muscularis propria and perceive passive and active tension [132, 134]. ICCs have been found in esophageal smooth muscle and the LES (intramuscular ICC; ICC‐IM) [135, 136]. ICC‐IMs may influence the release of neurotransmitters from nerve endings to the smooth muscle and thus participate in esophageal peristalsis [136, 137]. Additionally, the network of ICC‐IMs and IMAs may function as stretch receptors [132, 133]. IMAs consist of a branching array of vagal axons along smooth muscle, including the LES. Mucosal afferent endings can respond to various stimuli, including mechanical and chemical stimuli. While these nerves are not sensitive to intraluminal distention, light touch from bolus passage can be detected. Calcitonin gene‐related peptide (CGRP) positive afferent nerves have been demonstrated in esophageal mucosa [138, 139]. Esophageal sensory information also passes to the spinal cord and centrally via the sympathetics through the C1 to L2 dorsal root ganglia [23] and provides cognitive sensation and nociception rather than motor function [20].
Striated muscle
Motor innervation to the striated muscle esophagus originates in motor neurons of the nucleus ambiguus and is carried to the esophagus largely by the recurrent laryngeal nerve. The nerve fibers terminate in motor endplates in both circular and longitudinal layers [140] and release acetylcholine to contract the muscle through nicotinic muscarinic receptors [141]. The ganglion cells in the myenteric plexus send fibers to the motor endplates and contain NO, vasoactive intestinal peptide (VIP), galanin, and neuropeptide Y [142–146]. This coinnervation provides inhibitory modulation of striated muscle contraction and peristalsis through local and/or central reflexes [145, 146]. It is unclear whether vagal fibers from the SPG impact these neurons. IGLEs, considered to be sensory receptors, are present. ICCs are also present, but their role is unclear, although they may also function as sensory receptors 131, 147]. The region also receives sympathetic innervation, and sympathetic sensory information is passed from this region through segments C1–T8. 127].
Contraction of the striated muscle for both primary and secondary peristalsis is under central control of the SPG esophageal stage [5, 7, 35], with sequential excitation through vagal fibers [39, 40, 148]. This activity is sensitive to sensory feedback and may be modulated by local and/or central reflexes [145, 146, 149].
Smooth muscle
There is significant redundancy of control mechanisms for smooth muscle peristalsis that interact effectively for normal peristalsis. Vagal fibers enter the esophagus at different levels and travel various distances within the esophagus to reach the neurons within the intramural plexuses. Sympathetic supply arises from spinal segments T1–10 with post‐ganglionic fibers passing to the esophagus from paraspinal sympathetic ganglia 127]. These fibers also go mainly to the intramural plexuses, to modulate neuronal activity. Few sympathetic fibers go directly to the smooth muscle cells. The role of the sympathetics appears to be limited [150, 151], although activation of beta‐receptors causes membrane hyperpolarization and muscle relaxation [151, 152], and catecholamines may release other inhibitory peptides from nerves [153]. As in the striated muscle portion, the myenteric ganglion cells have many different peptides [143, 154, 155]. Some of these peptides may have a modulatory role. However, for practical purposes, functionally there are only two types of motor neurons: excitatory cholinergic neurons that also contain substance P; and inhibitory nitrergic (NO) neurons that also contain VIP.
The longitudinal muscle forms a continuous layer of smooth muscle cells that do not make gap junction contact with each other. ICCs are present in this layer in the human [156] and cat esophagus [131], but not the dog or opossum [135, 157, 158]. Nerve fibers enter this layer from the myenteric plexus.
The circular layer is not a continuous sheet of muscle cells but is separated into lamellae or muscle bundles by connective tissue septa that are in intimate contact with the myenteric plexus region [131, 156]. Smooth muscle cells make gap junction contacts between themselves and the ICCs, but not with nerves. The ICCs are found within the muscle bundles and in the connective tissue septa. There are few ICCs in the myenteric plexus region. It is proposed that many of these ICCs function as sensory receptors since the presence and structural integrity of some ICCs are dependent on the presence