[188].
Afferent sensory stimulation
The esophageal stage of the SPG is normally activated during swallowing [7], enhanced by pharyngeal and esophageal sensory feedback, but least prominent during the esophageal stage. Failed esophageal peristalsis in all or part of the esophagus is common in humans, particularly with “dry” swallows. The presence of a bolus increases the amplitude of the peristaltic wave and its completion [78, 189, 190]. Animal studies have been conflicting in determining the necessity for bolus stimulation of the esophagus for primary peristalsis to occur. In dogs that have a totally striated muscle esophagus, and with diversion of the bolus in the cervical esophagus, primary peristalsis is absent in the distal esophagus [191, 192]. In the decerebrate cat with absent cortical input and intact distal smooth muscle esophagus, the bolus must be present in the cervical esophagus for peristalsis to proceed [104]. In primates that also have a distal smooth muscle esophagus, the bolus is not always necessary [193]. Transcranial magnetic stimulation of the cortex in the anesthetized cat [50] or awake dog [194] can itself initiate swallowing. Transcranial magnetic stimulation does not initiate swallowing in the human, although muscles in the pharynx and upper and lower esophagus can be induced to contract [195–197]. The esophageal stage of the SPG must be adequately activated for primary esophageal peristalsis, and one or more of the three SPG inputs – cortical, pharyngeal, or esophageal – is sufficient for activation, with each input facilitating others [198]. However, involvement of all three may not be necessary, depending on species’ differences and experimental conditions.
The swallowed bolus is an important component of peristaltic integrity, and amplitude, duration, and velocity of the peristaltic wave are subject to the nature and size of the bolus. Sensory feedback regarding the swallowed bolus is transmitted by esophageal afferent nerves to the solitary nucleus, which modifies efferent output to the smooth esophageal muscles [199]. Bolus information can also modify peristalsis through intramural neuromuscular reflexes, thereby affecting the strength and speed of esophageal peristalsis [200–203]. Larger boluses and increased viscosity increase contraction amplitude and duration, and slow peristaltic velocity [189, 190, 200]. Additionally, hot water increases amplitude while decreasing the duration of contraction, whereas cold water decreases amplitude and increases the duration of contraction [199]. Increased intra‐abdominal pressure and esophageal obstruction also increase amplitude and slow velocity.
Under normal circumstances, secondary peristalsis is dependent on sensory activation of a central reflex, mediated by activation within the esophageal stage of the SPG [184, 204]. This is always true of the striated muscle esophagus because of its dependence on central control. Once initiated, this also activates neurons for the smooth muscle esophagus, and the contraction wave progresses distally in identical fashion to the primary wave [184, 205]. There is no convincing evidence that intramural neural or myogenic mechanisms stimulated locally in the smooth muscle segment could independently produce secondary peristalsis when central connections are intact. In the cat, vagal blockade in the neck abolishes secondary peristalsis [157]. However, local mechanisms in this segment can alter the response to the central control that is initiated by afferent signaling to the SPG, influenced by factors such as the location of the peripheral stimulus and whether the stimulus is a stationary distending balloon, collapsible barostat balloon, or movable bolus. When initiated by a moveable bolus or barostat balloon, secondary peristalsis proceeds relatively unaltered. A fixed distending balloon, not a physiologic stimulus, induces contractions proximal to the balloon and can significantly alter the distal contraction [40,206–212]. As with primary peristalsis, the local and central mechanisms must integrate effectively.
Muscle tone
Both the striated and smooth muscle esophagus exhibit a resting tone that can be measured by a barostat [207, 209]. In the smooth muscle esophagus, this tone is due to cholinergic excitation that is largely vagal dependent, modulated by nitrergic inhibition. The tone is influenced by afferent information, enhanced by intraluminal distention, and inhibited by a swallow [125].
Smooth muscle esophageal body: motor activity
Three control mechanisms interact and integrate effectively to ensure smooth muscle peristalsis: (i) the central SPG [5, 7, 26, 35], through sequential efferent signals to the esophagus via the vagus nerves [39, 213, 214]; (ii) an intramural neural mechanism that can result in peristalsis near the onset of vagal stimulation or intraluminal balloon distention (“on contraction” or “A wave”) or after the stimulus or distention are terminated (“off contraction” or “B wave”) [166,215–217]; and (iii) a myogenic mechanism [165, 218, 219]. Regardless of mechanism, swallow‐induced peristaltic contraction is highly atropine sensitive in the human, monkey, and (especially) cat [205, 210,220–222], suggesting mediation by intramural cholinergic neurons.
Central control mechanisms
The esophagus receives vagal input providing sequential activation to both the striated and smooth muscle segments during both primary and secondary peristalsis. Figure 5.11 illustrates this vagal activity in the baboon and opossum [39, 214]. The findings in the opossum indicate two different timings of vagal firing patterns: an early, rapid‐sequence group that would fit with early activation of inhibitory neurons; and a later, slower‐sequence group that mirrors the timing and velocity of the peristaltic contraction. It is not known if two firing patterns are present in other species. If initial inhibition and subsequent excitation is the function of these two groups, it has been assumed that the early group excites the inhibitory neurons, while the later group excites the excitatory neurons along the smooth muscle esophagus. It is unclear if the vagal fibers go directly to these neurons or are routed through interneuronal circuitry. However, this input must integrate effectively with the intramural mechanisms, including this circuitry and the muscle itself.
Figure 5.11 Vagus nerve firing patterns with esophageal peristalsis. The firing patterns of the vagus nerve during a swallow in the opossum (A) and the baboon (B). In the opossum, there is an early and a late sequential firing pattern, the later pattern corresponding to the timing and velocity of the esophageal peristaltic wave. In the baboon, only a sequential firing pattern timed with the presence of the esophageal contraction along the esophagus was recorded. UE, upper esophagus; ME, mid esophagus; LE, lower esophagus.
Sources: (A) Adapted from Gidda and Goyal [164] (B) Roman [39] with permissions of Elsevier.
Intramural neural control mechanisms
In 1970, Christensen demonstrated neurally mediated peristaltic contraction in the isolated opossum smooth muscle esophagus in vitro that followed intraluminal balloon distention or electrical stimulation to the external surface [173, 223]. These observations established the presence of a local mechanism capable of producing peristalsis. Thereafter, two main approaches have explored the neural mechanisms involved: studies of the intact animal with or without vagotomy, and studies of smooth muscle strips in vitro. The studies have elucidated much of the underlying physiology that can operate but have not clarified how the central and peripheral neural mechanisms interact under normal circumstances.
Dodds et al. stimulated the cut end of the vagus, stimulating all efferent and afferent fibers at once, and found two peripheral neural mechanisms for peristalsis: on contraction (A wave) and off contraction (B wave) [215–217]. The on contraction was induced by low‐frequency stimulation, was atropine sensitive, and had slow propagation velocity similar to normal peristalsis. The off contraction occurred at higher stimulating frequencies, was not atropine sensitive, and had a much more rapid propagation velocity. Varying other stimulus parameters as well can influence