This starts in the small intestine and moves into the stomach. Gas pain? Stool issues? Sign up for the best tips to take care of your stomach. Lee OY. Asian motility studies in irritable bowel syndrome. J Neurogastroenterol Motil. Drug-induced gastrointestinal disorders. Frontline Gastroenterol. Gastrointestinal motility disorders in inflammatory bowel diseases.
World J Gastroenterol. Lynch KL. Esophageal motility disorders. Merck Manual. Updated July Esophageal motility abnormalities in gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther. Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis. Neurogastroenterol Motil. Intestinal pseudo-obstruction. Updated February Patel KS, Thavamani A.
Physiology, peristalsis. Updated March 1, Katsanos KH, et al. Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page.
Like striated muscle in other parts of the body, the striated muscle segment of the esophagus is dependent on excitatory nerve activity from lower motor neurons. The striated muscle of the esophagus is innervated by myelinated vagal lower motor neurons whose cell bodies are located in the nucleus ambiguus and nucleus retrofacialis. These nerve fibers contain choline acetyltransferase and calcitonin gene-related peptide CGRP and synapse directly on the motor end plates. Acetylcholine is the primary neurotransmitter involved in activation of esophageal striated muscle.
The role of CGRP is unknown. Bilateral cervical vagotomy above the origin of the pharyngoesophageal branches abolishes peristalsis in the striated muscle esophagus. They used the central portion of the sectioned vagus in sheep to reinnervate the sternocleidomastoid and trapezius muscles from which they were able to record electrical activity. Activation of deglutition induced sequential contraction of the reinnervated muscles that coincided with peristaltic contractions simultaneously measured by intraluminal manometry.
A scant myenteric plexus does exist within the striated muscle esophagus, but its role in esophageal motor function is unclear. Interestingly, it has been demonstrated that motor end plates in the striated muscle esophagus are co-innervated by vagal lower motor neurons and nitrergic myenteric plexus neurons. Control of peristalsis in the smooth muscle segment of the esophagus is more complicated than in the adjacent striated muscle segment.
In the latter, the central nervous system not only initiates the primary and secondary peristaltic wave, but also completely controls the sequential nature of the contraction. In the smooth muscle esophagus, the central nervous system is required for activation of primary peristalsis and exerts some control over the sequencing of the peristaltic contractions. However, peristalsis can also occur independently of the central nervous system, which highlights the importance of neuromuscular mechanisms intrinsic to the esophageal wall in the generation of the peristaltic wave.
Cell bodies of vagal efferent fibers that innervate the smooth muscle esophagus are largely in the dorsal motor nucleus although at least in the cat a small proportion may also reside in the nucleus retroambiguus.
The observation that either bilateral cervical vagotomy or vagal cooling abolishes swallow-induced peristalsis in the smooth muscle esophagus clearly demonstrates that input from the central nervous system is required to initiate the primary peristaltic wave.
This was based on electromyographic recordings from baboon skeletal muscle that had been reinnervated by vagal efferent fibers, in which muscle spike bursts that coincided with peristaltic activity in the smooth muscle esophagus were recorded.
The pattern of this muscle discharge was sequential, indicating that vagal preganglionic fibers destined for the smooth muscle esophagus were being activated by a central sequencing mechanism. It was suggested that these vagal preganglionic efferent fibers synapse on postganglionic cholinergic fibers, which in turn sequentially activate the smooth muscle.
However, these studies do not explain the initial inhibitory discharge that occurs prior to peristaltic contraction in response to deglutition. Gidda and Goyal 35 recorded swallow-evoked potentials from single cervical vagal efferent fibers in the opossum and were able to distinguish two types of efferent discharge based on the latency to firing. Short latency fibers begin firing within 1 second of the onset of swallowing, whereas long latency fibers had latencies ranging between 1 and 5 seconds.
It was postulated that short latency discharges correlated with the initial inhibition to the esophagus and that long latency discharges correlated with peristaltic contractions. These experimental data suggested that in addition to initiating primary peristalsis, vagal efferent discharge might also modulate the speed, amplitude, and duration of the peristaltic wave.
The peripheral neuromuscular control mechanisms involved in peristalsis of the esophageal circular smooth muscle has been an area of intense interest and investigation for many years. A number of observations clearly establish the importance of intrinsic neuromuscular mechanisms in the generation of the peristaltic wave. As mentioned above, sequential firing does occur in vagal efferent nerves, and the vagus is needed for initiation of primary peristalsis.
However, peristalsis can be induced by local distention and electrical stimulation of an esophagus devoid of extrinsic innervation. Furthermore, simultaneous electrical activation of all vagal efferent nerve fibers induces peristalsis after a variable delay, rather than an immediate simultaneous contraction 36, 37, 38, 39 Figure 3. This indicates the prime importance of peripheral neuromuscular mechanisms in the generation of peristalsis.
Swallowing a evokes a peristaltic wave of contraction that migrates smoothly from the striated to smooth muscle esophagus. Simultaneous electrical activation of all vagal efferent neurons b produces simultaneous contractions in the striated muscle esophagus, which would be expected based on the direct innervation of this muscle by the vagal efferent neurons.
However, in the smooth muscle segment a peristaltic wave is induced. This is because intrinsic neurons activated by vagal efferent nerve stimulation are capable of evoking a peristaltic contraction without the need for centrally mediated sequencing. Tension recording studies of isolated circular smooth muscle strips that have intrinsic but not extrinsic innervation have elegantly demonstrated an intrinsic "latency gradient" of contraction along the esophagus that appears to contribute to the generation of the peristaltic wave.
Short-duration electrical stimulation of the intrinsic nerves of a circular smooth muscle strip results in a contraction that occurs after the stimulus has ended the so-called off response.
The onset of this contraction relative to the stimulus increases in strips taken from more aboral segments of the smooth muscle esophagus Figure 4. This latency gradient has been shown to relate to the initial inhibition or hyperpolarization that occurs upon nerve stimulation.
In other words, with nerve stimulation there is first release of an inhibitory neurotransmitter that causes hyperpolarization of the membrane. The duration of this hyperpolarization is longer aborally, 41 so that the ensuing contraction is delayed aborally.
This initial hyperpolarization of the circular smooth muscle membrane potential has also been recorded in the opossum in vivo in response to swallows.
It could represent a relative increase in the release or local effects of inhibitory neurotransmitter distally, or alternatively, a relative increase in excitatory neurotransmitter release or effects proximally. There is no direct evidence in support of either of these possibilities, but studies in several species 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 have shown that atropine delays the onset of peristaltic contractions, with a greater effect in the proximal than distal esophagus, whereas inhibition of nitric oxide NO shortens the latency of contraction, with a more pronounced effect distally than proximally see below.
To date, there has been no morphologic evidence of a gradient in the density of cholinergic or nitrergic innervation along the esophagus. This raises the possibility that intrinsic differences in smooth muscle responses along the esophagus may result in a varied response to the same quantum of released neurotransmitter.
There is some evidence in support of this hypothesis. Decktor and Ryan 56 noted a decrease in resting membrane potential along the smooth muscle portion of the opossum esophagus, with resting membrane potential being less negative distally.
A gradient in potassium content along the opossum smooth muscle esophagus has also been reported. More recently, Diamant and colleagues 59, 60, 61, 62, 63 have reported a number of regional myogenic differences along the feline smooth muscle esophagus, which may contribute to different responses to neurotransmitters.
These differences include the following: 1 A more depolarized resting membrane potential was found at 4 cm as compared to 2 cm above the LES , owing at least partly to higher sodium permeability distally. Stimulation results in phasic contraction after a variable delay.
The latency to onset of this contraction increase progressively in strips taken from more aboral segments of the smooth muscle esophagus. This demonstrates the existence of an "intrinsic latency gradient" of contraction along the esophagus, which contributes to the generation of a peristaltic wave. Thus, there must be mechanisms other than the intrinsic latency gradient to explain peristalsis. Experiments in which simultaneous electrical and mechanical activity were recorded in both the proximal and distal opossum smooth muscle esophagus have helped clarify the discrepancy between the in vitro and in vivo observations.
In keeping with the electrophysiologic and muscle strip studies, the duration of the initial hyperpolarization was slightly longer distally than proximally, but this difference was insufficient to explain the marked delay of esophageal contraction in the distal versus the proximal smooth muscle esophagus.
Rather, in the distal esophagus the initial monophasic inhibitory potential was followed by a second wave of hyperpolarization before the membrane potential rebounded into depolarization and initiation of spike potentials Figure 5.
It was suggested that this secondary hyperpolarization is likely due to reactivation of descending inhibitory neurons by distention or contraction of the more proximal esophagus in the course of peristalsis Figure 6.
This suggests that intramural descending inhibitory pathways are crucial in generating the peristaltic wave. Subsequent studies in the opossum have demonstrated that localized distention appears to directly activate intrinsic nitrergic inhibitory neurons that send long aboral projections. The peristaltic reflex was then activated by distending an intraluminal balloon in the proximal segment, whereas electrical and mechanical responses were recorded in the distal segment. Interestingly, whereas tetrodotoxin placed in the intermediate chamber abolished the descending peristaltic reflex, removing calcium and adding high concentrations of magnesium to the intermediate chamber, which blocks synaptic transmission, had no effect, indicating that the intramural neurons mediating this response traveled for at least 3 cm without synapsing on interneurons.
Furthermore, although removing calcium from the distending chamber inhibited the response, this was likely due to an effect on muscle tension generation in response to stretch, as application of antagonists of all known esophageal neurotransmitters to the distending chamber had no effect.
Also, the calcium channel blocker nifedipine, when placed in the oral distending chamber, decreased the muscle tension generated in response to distention and also inhibited the distal response. With primary peristalsis, note that the delay in onset of depolarization, spike burst, and esophageal contraction in the distal esophagus relates to a marked secondary hyperpolarization arrow.
However, when balloon distention induces a secondary peristaltic wave of normal velocity right panel , the marked delay in onset of contraction distally correlates with a secondary hyperpolarization arrow that is likely due to reactivation of intrinsic descending inhibitory pathways by contractions occurring upstream. Source: Paterson, 44 with permission.
With the initial stimulation, be it swallowing or distention, there is a short-lived hyperpolarization that is slightly longer in more aboral region of the esophagus. Intrinsic descending inhibitory neurons can then be continuously reactivated by contraction or bolus distention as it migrates down the esophagus. Vagal efferent neurons involved in esophageal peristalsis synapse on both inhibitory and excitatory myenteric neurons. Ganglionic transmission is predominantly nicotinic, although there may be associated muscarinic and serotonergic transmission as well.
One stains for NO synthase and vasoactive intestinal peptide, and the other for choline acetyl transferase and substance P. Nitric oxide is the predominant inhibitory neurotransmitter, whereas acetylcholine, acting on muscarinic receptors, is the predominant excitatory neurotransmitter.
Evidence for this dual innervation comes from a number of sources. In the opossum model, nerve stimulation of isolated circular smooth muscle strips produces a predominant "off" contraction i. These observations are supported by studies using vagal efferent nerve stimulation.
These are often peristaltic in nature, but this can be influenced by adjusting the electrical stimulus parameters. If a long stimulus train is used, however, both an intrastimulus contraction A wave and a poststimulus contraction B wave are frequently observed.
Whether A waves, B waves, or both are induced by long train vagal efferent stimulation depends on the stimulus frequency used. Low-frequency stimulation favors A waves, whereas high-frequency stimulation favors B waves, implying that intrinsic cholinergic and nitrergic neurons respond differently to different intensity stimuli.
Interestingly, administration of atropine not only blocks A waves, but also unmasks or enhances B waves, whereas NOS inhibition does the opposite Figure 7. It thus appears that the normal peristaltic wave is a result of blended innervation that may vary along the esophagus. Cholinergic neurons activate contraction by directly depolarizing the muscle. On the other hand, nitrergic neurons presumably cause contraction through a "rebound" depolarization following an initial hyperpolarization; that is, NO serves as both an inhibitory and excitatory neurotransmitter.
Subsequent administration of atropine abolishes primary peristalsis in the opossum smooth muscle esophagus. As alluded to above, significant regional differences in the balance between cholinergic and noncholinergic i. For instance, in vitro muscle studies using opossum esophageal circular smooth muscle have shown that atropine has a greater effect on amplitude and latency of contraction in the proximal as compared to the distal esophagus.
Amplitude of contraction is also preferentially affected proximally. On the other hand, inhibition of NO shortens the latency and decreases contraction amplitude more so in the distal than in the proximal smooth muscle esophagus. The physiologic role of other neurotransmitters found within the smooth muscle esophagus is unclear, as studies often fail to clearly differentiate a pharmacologic from a physiologic effect.
Using an antagonist of the neurokinin-2 receptor, Krysiak and Preiksaitis 78 found that tachykinins contribute to part of the noncholinergic excitatory response evoked by electrical stimulation of human circular smooth muscle strips. Enkephalins also may modulate peristalsis by presynaptic inhibition or excitation of neurotransmitters directly responsible for peristalsis. Exogenously administered galanin appears to inhibit noncholinergic esophageal nerves, 83 but a galanin antagonist had no noticeable effect on esophageal peristalsis.
In recent years there has been considerable interest in the role of interstitial cells of Cajal ICCs in the control of gastrointestinal GI motility. These cells are believed to be the pacemakers for the stomach and intestine. There is also evidence that they are intercalated between nerves and muscle, and therefore serve as relay stations in neuromuscular transmission.
Spontaneous rhythmic contractions have been recorded from esophageal longitudinal smooth muscle at rest, 85, 86 but these contractions are nifedipine-sensitive and unlikely to be due to pacing by ICCs. However, morphologic studies have reported intercalation of ICCs between nerve endings and esophageal smooth muscle cells in the opossum. This is largely because the ICC-deficient mouse, which has been used for physiologic studies, does not have a smooth muscle esophageal body.
It has been speculated that esophageal body ICCs are involved in neuromuscular transmission, or serve as tension receptors that then relay information to intrinsic or extrinsic neurons. From the above discussion it is clear that both NO and acetylcholine are crucial neurotransmitters in generation of the peristaltic wave. Nitric oxide produces hyperpolarization of the circular smooth muscle cell membrane via a cyclic guanosine monophosphate cGMP -dependent pathway, 89, 90 thereby causing inhibition of voltage-dependent calcium entry.
There has been considerable controversy surrounding the mechanisms whereby NO induces membrane hyperpolarization. In further support of this, NO donors were reported to activate multiple types of potassium channels and whole cell potassium currents in different smooth muscles, including esophageal. However, selective potassium channel blockers failed to abolish the nitrergic IJP in opossum esophageal circular smooth muscle, 93, 94 suggesting that opening of potassium channels may not underlie the hyperpolarization caused by neurally released NO.
Based on experiments utilizing chloride substitution and application of the anion channel blocker 4,4'—diisothiocyanostilbine—2,2'—disulfonic acid, Crist et al.
Subsequently, Zhang et al. More recently, Zhang and Paterson reported that the nitrergic IJP could be blocked by two different calcium-activated chloride channel blockers, namely niflumic acid and 9-anthroic acid. Furthermore, they provided evidence that the nitrergic IJP is dependent on activation of myosin light chain kinase. At rest, the membrane potential of esophageal circular smooth muscle cells shows apparently random membrane potential fluctuations of 1 to 3 mV. Inhibitors of sarcoplasmic reticulum function or blockers of chloride channels markedly attenuate these random fluctuations, suggesting that they are due to spontaneous activation of chloride channels, primed by calcium release from the sarcoplasmic reticulum.
Acetylcholine affects many ionic currents in esophageal circular smooth muscle including calcium-sensitive chloride and nonselective cation currents. Chloride currents cause depolarization of the smooth muscle membrane, which in turn leads to entry of extracellular calcium via voltage-sensitive calcium channels.
Activation of nonselective cation channels does not lead to significant membrane depolarization. Their activation may result in calcium entry by non—voltage-dependent mechanisms. The second messenger pathways involved in acetylcholine-induced contraction are complex, and have recently been reviewed Figure 8.
Acetylcholine acts on muscarinic type 2 M 2 receptors that are linked to G i3 -type G proteins within the muscle membrane. Of interest, esophageal peristalsis can be induced in the smooth muscle esophagus in the presence of tetrodotoxin, which blocks all sodium channel—mediated action potentials in neurons. It is believed that there is polarization of the muscle-to-muscle communication such that depolarization of one smooth muscle cell will result in electrotonic spread of current to adjacent muscle cells in an aboral direction.
Secondary peristalsis refers to peristalsis activated by esophageal distention. This can occur physiologically by food left behind after the primary peristaltic wave has passed, or by refluxed contents from the stomach. Unlike primary peristalsis, secondary peristalsis is not accompanied by deglutition with associated pharyngeal and upper esophageal sphincter motor function.
In the striated muscle esophagus, distention activates a peristaltic reflex that is mediated by central mechanisms; distention activates vagal afferents, which in turn leads to sequential vagal efferent discharge to the striated musculature of the proximal esophagus.
Indeed, luminal distention of an esophagus excised and placed in a tissue bath results in a peristaltic contraction. A similar, atropine-sensitive contraction orad to the balloon is also seen in humans. During the distending stimulus there is a descending inhibitory discharge, mediated predominantly by NO , which results in hyperpolarization and inhibition of the circular smooth muscle.
This peristaltic reflex is quite different from that described in the intestine, where the proximal excitation does not involve extrinsic innervation.
Rather, descending nitrergic neurons appear to be activated directly by the distending stimulus and send long descending inhibitory neural connections to the distal esophagus. Understandably, investigators have focused on the role of the circular smooth muscle in esophageal peristalsis; however, the longitudinal muscle also contracts in sequential fashion during peristalsis and appears to play a role in bolus transport.
To date, studies on the physiology of the longitudinal muscle have focused entirely on the smooth muscle esophagus. Whereas it is easy to conceptualize how aborally progressive lumen occluding contractions of the circular muscle serve to push the bolus toward the stomach, it is less obvious how longitudinal muscle contraction might be involved in this process.
It has been proposed that the longitudinal smooth muscle contraction may facilitate peristalsis by two mechanisms: 1 by shortening the esophagus, the esophageal radius must increase, thereby increasing the lumen size ahead of the oncoming bolus ; 2 longitudinal contractions tend to slide the esophagus over the bolus and increase the density of the circular muscle fibers orad to the bolus, which in turn increase the efficiency of the circular muscle contraction 2.
Recent studies using a mathematical model based on fluid theory have provided evidence that local longitudinal muscle contraction results in marked reduction in local pressure and shear stress in the zone of circular muscle contraction, thereby reducing the peak contractile pressure required for bolus transit.
Studies in the opossum have shown that the longitudinal muscle contracts sequentially in an aboral direction during primary peristalsis. The duration of longitudinal muscle contraction also appears to vary along the esophagus. Similar to circular muscle, contraction is longer distally than proximally. In vivo studies in the opossum model have also shown that the primary neurotransmitter involved in longitudinal smooth muscle contraction is acetylcholine.
The muscarinic antagonist atropine virtually abolishes longitudinal muscle contraction and esophageal shortening in response to swallowing and vagal stimulation. In vitro studies have also shown that longitudinal muscle contraction is predominantly mediated by cholinergic neurons; however, with certain stimulus parameters a slowly developing and sustained longitudinal muscle contraction can be evoked, which is abolished by substance P desensitization.
However, it may play a role in the reflex longitudinal muscle contraction that occurs with acid reflux into the esophagus. Nitric oxide has been reported to cause paradoxical contraction of esophageal longitudinal smooth muscle, 86, , but it is unclear whether this neurotransmitter is involved in physiologic contraction of this muscle layer. Nitric oxide synthase inhibition appeared to decrease swallow-induced esophageal shortening in the cat, but evidence for a NO-mediated neural response could not be found in vitro in this species.
Although there is evidence that the longitudinal smooth muscle may participate in deglutitive inhibition, there is no evidence to date that this is related to direct inhibitory innervation to the longitudinal smooth muscle. Elegant studies in which electrical activity was recorded from a flap of isolated longitudinal smooth muscle in vivo showed no evidence of an inhibitory junction potential occurring during primary peristalsis. Little is known about the physiologic role of the muscularis mucosa during peristalsis.
It may contract primarily in response to luminal stimuli, thereby evoking movement of esophageal mucosa. It may also serve to hold the normally loosely attached overlying mucosa in place, thereby preventing excessive movement of the mucosa during bolus movement 2.
Studies on the physiology and pharmacology of this muscle layer have been carried out. There also appears to be a more sustained or tonic contraction due to release of substance P. Esophageal peristalsis, which can be triggered by either swallowing or local esophageal distention, serves to propel esophageal contents into the stomach.
This is orchestrated by a complicated interaction between the central nervous system and the myenteric plexus, with the latter predominating in the smooth muscle esophagus. Esophageal peristalsis consists of sequential contraction of the circular muscles of the muscularis propria, which is largely mediated by acetylcholine.
This sequential contraction serves to occlude the esophageal lumen and push the bolus aborally. An important component in this process is the nitrergic inhibition of the circular smooth muscle that occurs aboral to the oncoming bolus. In addition, sequential contraction of longitudinal muscle also occurs during peristalsis. This serves to shorten the esophagus and increase the cross-sectional diameter, thereby facilitating bolus transport. There remains much to be learned about the physiologic control of esophageal peristalsis, including 1 the precise mechanisms whereby cholinergic and noncholinergic mainly nitrergic innervations interact to generate a peristaltic wave; 2 the cellular mechanisms involved in the nitrergic inhibition of esophageal circular smooth muscle; 3 the role of interstitial cells of Cajal in coordinating esophageal peristalsis; and 4 the role of other neurotransmitters in modulating peristalsis.
The word is derived from New Latin and comes from the Greek peristaltikos , peristaltic, from peristellein , "to wrap around," and stellein , "to place. In much of the gastrointestinal tract , smooth muscles contract in sequence to produce a peristaltic wave which forces a ball of food called a bolus while in the esophagus and gastrointestinal tract and chyme in the stomach along the gastrointestinal tract. Peristaltic movement is initiated by circular smooth muscles contracting behind the chewed material to prevent it from moving back into the mouth, followed by a contraction of longitudinal smooth muscles which pushes the digested food forward.
After food is chewed into a bolus, it is swallowed to move it into the esophagus. Smooth muscles will contract behind the bolus to prevent it from being squeezed back onto the mouth, then rhythmic, unidirectional waves of contractions will work to rapidly force the food into the stomach.
This process works in one direction only and its sole purpose is to move food from the mouth into the stomach. Once processed and digested by the stomach, the milky chyme is squeezed through the pyloric valve into the small intestine.
Once past the stomach a typical peristaltic wave will only last for a few seconds, traveling at only a few centimeters per second. Its primary purpose is to mix the chyme in the intestine rather than to move it forward in the intestine. Through this process of mixing and continued digestion and absorption of nutrients, the chyme gradually works its way through the small intestine to the large intestine.
During vomiting the direction of peristalsis reverses to move food back into the stomach, though the propulsion of food up the esophagus and out the mouth comes from contraction of the abdominal muscles ; peristalsis does not reverse in the esophagus. As opposed to the more continuous peristalsis of the small intestines, fecal contents are propelled into the large intestine by periodic mass movements.
These mass movements occur one to three times per day in the large intestines and colon, and help propel the contents from the large intestine through the colon to the rectum.
0コメント