Distension-induced Secondary Peristalsis Research Articles

Effects of capsaicin on esophageal peristalsis in humans using high resolution manometry.

Capsaicin-containing red pepper sauce suspension augments esophageal contraction amplitude on conventional manometry. This study used high-resolution manometry (HRM) to investigate if capsaicin infusion modulates segmental esophageal smooth muscle peristalsis in healthy adults. Sixteen healthy volunteers (mean age 37 years, 14 male) underwent HRM for the evaluation of primary peristalsis and secondary peristalsis using slow and rapid air distensions. Both primary and secondary peristalsis were assessed following infusions of capsaicin-containing red pepper sauce and saline. Capsaicin infusion significantly increased heartburn symptoms compared to saline infusion (p < 0.001), and significantly decreased threshold volumes of secondary peristalsis during rapid air distensions (p = 0.02). The frequency of secondary peristalsis during rapid air distensions was significantly increased by capsaicin infusion (p = 0.03). Neither capsaicin infusion (p = 0.06) nor saline infusion (p = 0.27) altered threshold volume during slow air distensions. Capsaicin infusion significantly increased distal contractile integral (DCI) of primary peristalsis (p = 0.04), particularly in the proximal smooth muscle segment (p = 0.048). It enhanced secondary peristalsis during rapid air distensions (p = 0.003) but not during slow air distension (p = 0.23). Saline infusion significantly increased DCI of secondary peristalsis during rapid air distension (p = 0.01). Augmentation of distension-induced secondary peristalsis can be modulated by activation of capsaicin-sensitive afferents similar to mechanosensitive afferents. Capsaicin-induced augmentation of primary peristalsis isolates to the cholinergic-mediated proximal smooth muscle segment, which warrants study in ineffective esophageal motility to determine therapeutic potential.

Effects of menthol on esophageal motility in humans: Studies using high-resolution manometry.

The cold receptor, transient receptor potential melastatin 8 (TRPM8), has been reported to be expressed in esophageal vagal afferents. Esophageal infusion of menthol modulates esophageal perception in reflux patients via TRPM8, but the effects of menthol on esophageal motility are not well investigated. This study aimed to test the hypothesis whether the infusion of menthol into the esophagus could affect esophageal peristaltic characteristics. Eighteen healthy adults (men 13, mean age 27) underwent high-resolution manometry (HRM) using a catheter with the injection port located in mid-esophagus. Primary peristalsis was performed with ten wet swallows, while secondary peristalsis was generated by 10 rapid air injections. Two different sessions were randomly performed including acute administration of menthol (3mM) and the placebo. Menthol significantly decreased upper esophageal (UES) pressure of primary peristalsis than the placebo (p=0.019). There was no difference in distal contractile integral (p=0.33), distal latency (p=0.86), basal lower esophageal sphincter pressure (p=0.19), or 4-second integrated relaxation pressure (p=0.75) between menthol and placebo. Menthol significantly decreased the frequency of secondary peristalsis subsequent to the administration of menthol during rapid injections with 20mL air (p=0.04). Intraluminal infusion of menthol reduces UES basal pressure and inhibits peristaltic frequency of secondary peristalsis. The data suggest that the triggering of secondary peristalsis is probably modulated by TRPM8-sensitive mechanoreceptors; however, the activation of TRPM8 from menthol does not alter esophageal motility following deglutition or distension-induced secondary peristalsis.

Effects of codeine on esophageal peristalsis in humans using high resolution manometry.

Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension-induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults. Eighteen healthy volunteers (13 men, mean age 27.5years, aged 20-43years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid-esophagus. Secondary peristalsis was performed with 10 and 20mL rapid air injections. Two different sessions including acute administration of codeine (60mg) or the placebo were randomly performed. Codeine significantly increased 4-s integrated relaxation pressure (IRP-4s) (P=0.003) and shortened distal latency (DL) (P=0.003) of primary peristalsis. The IRP-4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10mL (P=0.048) and 20mL (P=0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10mL than the placebo (P=0.007), but not for air injection with 20mL (P=0.305). In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.

Effects of esophageal acid infusion vs mosapride on distension-induced secondary peristalsis in humans.

Secondary peristalsis contributes to the clearance of the refluxate from the esophagus. Acute administration of 5-hydroxytryptamine 4 (5-HT4 ) receptors agonist, mosapride or esophageal infusion of hydrochloric acid (HCl) facilitates secondary peristalsis. The aim of this study was to determine whether esophageal acid infusion and administration of mosapride had different effects on secondary peristalsis. Secondary peristalsis was performed with esophageal distension with rapid and slow air injections in 16 healthy subjects. We performed two separate sessions with HCl (0.1 N) and 40 mg oral mosapride to compare their influence on secondary peristaltic parameters. The threshold volume of secondary peristalsis was significantly lower with HCl infusion than mosapride (P = 0.01) by slow air injections. The threshold volume to generate secondary peristalsis was significantly lower with HCl infusion than mosapride (P = 0.002) by rapid air injections. More secondary peristalsis was trigged by rapid air injections after HCl infusion than mosapride (P = 0.003). Infusion of HCl or mosapride administration has similar effects on peristaltic wave amplitude and duration of primary and secondary peristalsis. Acute esophageal acid infusion can induce greater mechanosensitivity to distension-induced secondary peristalsis than 5-HT4 receptors agonist mosapride. The data suggest that acid-sensitive afferents are more likely to contribute to sensory modulation of esophageal secondary peristalsis; however, the motility aspects of secondary peristalsis are comparable between acute esophageal acidification and 5-HT4 receptors activation via mosapride.

Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid-induced excitation of secondary peristalsis but not heartburn sensation.

Acute esophageal acid infusion promotes distension-induced secondary peristalsis. The gamma-aminobutyric acid receptor type B (GABA-B) receptors activation inhibits secondary peristalsis. This study aimed to test the hypothesis whether acid excitation of secondary peristalsis can be influenced by baclofen. Secondary peristalsis was performed with intra-esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1N HCl following pretreatment with placebo or baclofen was randomly performed at least 1week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol. The intensity of heartburn symptom in response to esophageal acid infusion was significantly greater with baclofen than the placebo (P=0.002). The threshold volume of secondary peristalsis during slow air injections in response to acid infusion was significantly greater with baclofen than the placebo (P=0.001). Baclofen significantly increased the threshold volume of secondary peristalsis during rapid air injections in response to acid infusion (P=0.001). The frequency of secondary peristalsis in response to acid infusion was significantly decreased by baclofen as compared with the placebo (P=0.001). Baclofen significantly decreased peristaltic amplitudes in response to acid infusion during rapid air injections (P=0.007). Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid excitation of secondary peristalsis in human esophagus, which is probably mediated by both muscular and mucosal mechanoreceptors. This work supports the evidence of potential involvement of GABA-B receptors in negative modulation of acid excitation of esophageal perception as well as secondary peristalsis.

Axial Movements and Length Changes of the Human Lower Esophageal Sphincter During Respiration and Distension-induced Secondary Peristalsis Using Functional Luminal Imaging Probe.

Background/AimsEfficient transport through the esophago-gastric junction (EGJ) requires synchronized circular and longitudinal muscle contraction of the esophagus including relaxation of the lower esophageal sphincter (LES). However, there is a scarcity of technology for measuring esophagus movements in the longitudinal (axial) direction. The aim of this study is to develop new analytical tools for dynamic evaluation of the length change and axial movement of the human LES based on the functional luminal imaging probe (FLIP) technology and to present normal signatures for the selected parameters.MethodsSix healthy volunteers without hiatal hernia were included. Data were analyzed from stepwise LES distensions at 20, 30, and 40 mL bag volumes. The bag pressure and the diameter change were used for motion analysis in the LES. The cyclic bag pressure frequency was used to distinguish dynamic changes of the LES induced by respiration and secondary peristalsis.ResultsCyclic fluctuations of the LES were evoked by respiration and isovolumetric distension, with phasic changes of bag pressure, diameter, length, and axial movement of the LES narrow zone. Compared to the respiration-induced LES fluctuations, peristaltic contractions increased the contraction pressure amplitude (P < 0.001), shortening (P < 0.001), axial movement (P < 0.001), and diameter change (P < 0.01) of the narrow zone. The length of the narrow zone shortened as function of the pressure increase.ConclusionsFLIP can be used for evaluation of dynamic length changes and axial movement of the human LES. The method may shed light on abnormal longitudinal muscle activity in esophageal disorders.

Effects of prucalopride on esophageal secondary peristalsis in humans.

Objectives:Prucalopride, a high-affinity 5-hydroxytrypatamine 4 (5-HT4) receptors agonist, has been shown to improve colon motility in adults. Secondary peristalsis helps the clearance of retained food bolus and refluxate from the esophagus, but the effects of prucalopride on esophageal secondary peristalsis are unknown. We aimed to assess the effects of prucalopride on distension-induced secondary peristalsis in healthy adults.Methods:Two separate sessions with prucalopride and placebo were performed in 11 healthy adults to test the effects on secondary peristalsis. Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air after a baseline recording of esophageal motility.Results:Prucalopride significantly decreased the threshold volume to generate secondary peristalsis during slow air injection (9.8±1.4 vs. 14.4±0.9 ml, P=0.005) and rapid air injection (3.9±0.3 vs. 5.2±0.4 ml, P=0.008). Secondary peristalsis was generated more frequently after application of prucalopride (80% (70–100%) vs. 70% (60–73%), P=0.01). Prucalopride increased the wave amplitude of distal esophagus during slow air injection (147.9±28.5 vs. 104.2±16.8 mm Hg, P=0.048) and rapid air injection (128.0±13.3 vs. 105.7±12.3 mm Hg, P=0.016). Primary peristaltic amplitudes were also significantly increased by the application of prucalopride.Conclusions:Acute administration of prucalopride enhances mechanosensitivity of distension-induced secondary peristalsis and promotes esophageal contractility in healthy adults. Whether prucalopride could be a therapeutic option for the treatment of subjects with esophageal hypomotility needs further study.

Differences in the Control of Secondary Peristalsis in the Human Esophagus: Influence of the 5-HT4 Receptor versus the TRPV1 Receptor.

ObjectiveAcute administration of 5-hydroxytryptamine4 (5-HT4) receptor agonist, mosapride or esophageal infusion of the transient receptor potential vanilloid receptor-1 (TRPV1) agonist capsaicin promotes secondary peristalsis. We aimed to investigate whether acute esophageal instillation of capsaicin-containing red pepper sauce or administration of mosapride has different effects on the physiological characteristics of secondary peristalsis.MethodsSecondary peristalsis was induced with mid-esophageal air injections in 14 healthy subjects. We compared the effects on secondary peristalsis subsequent to capsaicin-containing red pepper sauce (pure capsaicin, 0.84 mg) or 40 mg oral mosapride.ResultsThe threshold volume for generating secondary peristalsis during slow air distensions was significantly decreased with capsaicin infusion compared to mosapride (11.6 ± 1.0 vs. 14.1 ± 0.8 mL, P = 0.02). The threshold volume required to produce secondary peristalsis during rapid air distension was also significantly decreased with capsaicin infusion (4.6 ± 0.5 vs. 5.2 ± 0.6 mL, P = 0.02). Secondary peristalsis was noted more frequently in response to rapid air distension after capsaicin infusion than mosapride (80% [60–100%] vs. 65% [5–100%], P = 0.04). Infusion of capsaicin or mosapride administration didn’t change any parameters of primary or secondary peristalsis.ConclusionsEsophageal infusion with capsaicin-containing red pepper sauce suspension does create greater mechanosensitivity as measured by secondary peristalsis than 5-HT4 receptor agonist mosapride. Capsaicin-sensitive afferents appear to be more involved in the sensory modulation of distension-induced secondary peristalsis.

Tu1426 Differences in the Control of Distension-Induced Secondary Peristalsis in Human Esophagus: the Role of 5-HT4 Receptor Versus TRPV1 Receptor

Tu1426 Differences in the Control of Distension-Induced Secondary Peristalsis in Human Esophagus: the Role of 5-HT4 Receptor Versus TRPV1 Receptor

Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans.

The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p<0.001) and rapid air injections (p=0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception (p<0.001), but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion (p=0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p=0.003) and rapid air injections (p=0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p=0.0005) and rapid air injections (p=0.003). Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus.

Comparable effects of capsaicin‐containing red pepper sauce and hydrochloric acid on secondary peristalsis in humans

We aimed to evaluate whether acute esophageal instillation of capsaicin and hydrochloric acid had different effects on distension-induced secondary peristalsis. Secondary peristalsis was induced by slow and rapid air injections into the mid-esophagus after the evaluation of baseline motility in 16 healthy subjects. The effects on secondary peristalsis were determined by esophageal instillation with capsaicin-containing red pepper sauce (pure capsaicin, 0.84 mg) and hydrochloric acid (0.1 N). The administration of capsaicin induced a significant increase in the visual analogue scale score for heartburn as compared with hydrochloric acid (P = 0.002). The threshold volume for generating secondary peristalsis during slow and rapid air distensions did not differ between capsaicin and hydrochloric acid infusions. Hydrochloric acid significantly increased the frequency of secondary peristalsis in response to rapid air distension compared with capsaicin infusion (P = 0.03). Pressure wave amplitude during slow air distension was greater with the infusion of hydrochloric acid than capsaicin infusion (P = 0.001). The pressure wave duration during rapid air distension was longer after capsaicin infusion than hydrochloric acid infusion (P = 0.01). The pressure wave amplitude during rapid air distension was similar between capsaicin and hydrochloric acid infusions. Despite subtle differences in physiological characteristics of secondary peristalsis, acute esophageal instillation of capsaicin and hydrochloric acid produced comparable effects on distension-induced secondary peristalsis. Our data suggest the coexistence of both acid- and capsaicin-sensitive afferents in human esophagus which produce similar physiological alterations in secondary peristalsis.

Influence of Intraluminal Acidification on Esophageal Secondary Peristalsis in Humans

Secondary peristalsis contributes to clearance of retained refluxate or material from the esophagus. The goal of our study was to investigate the effects of hydrochloric acid (HCl) on physiological characteristics of esophageal secondary peristalsis in healthy adults. After recording esophageal motility baseline for primary peristalsis, secondary peristalsis was stimulated with slow and rapid air injections in the mid-esophageal in 16 healthy subjects. Normal saline and HCl (0.1 N) were separately infused into the esophagus to test whether they had effects on secondary peristalsis. After infusion of HCl, the threshold volume to generate secondary peristalsis was significantly decreased during rapid and slow air infusions (both P < 0.05). The frequency of secondary peristalsis was increased after HCl infusion (90 % [72.5-100 %] versus 85 % [72.5-90 %], P = 0.002). Infusion of HCl significantly increased pressure wave amplitude during rapid and slow air infusions (both P < 0.05). Infusion of saline did not affect any parameters of secondary peristalsis. The occurrence of heartburn was generated in 7 of 16 subjects after infusion of HCl with an increase in visual analogue scale score (12.5). Our data show that acute esophageal acid infusion enhances sensitivity of distension-induced secondary peristalsis and enhances secondary peristaltic activity. The study supports the evidence of the presence of acid-sensitive afferents in the modulation of distension-induced secondary peristalsis in humans.

Mechanisms of Esophageal Distension-Induced Secondary Peristalsis in Human: Studies With Baclofen and Mosapride

Mechanisms of Esophageal Distension-Induced Secondary Peristalsis in Human: Studies With Baclofen and Mosapride

Heterogeneity in Esophageal Motility in Reflux Patients With Different Symptom Presentation: Studies With Combined Impedance and Manometry

peristalsis could be modulated by baclofen and mosapride. Methods: In all 15 healthy subjects (5 female, mean age 22, range 20-26 yr), secondary peristalsis was generated by slow and rapid mid-esophageal injections of air after a baseline recording of esophageal motility. Three separate sessions with 40 mg oral baclofen, 40 mg oral mosapride or placebo were randomly performed to test their effects on esophageal secondary peristalsis with at least a 1-week interval. Results: Baclofen significantly increased the threshold volume for triggering secondary peristalsis during slow air distension (P = 0.003) and rapid air distension (P = 0.002). Baclofen significantly reduced the rate of secondary peristalsis by rapid air distension from 90% to 30% (P = 0.0002). Despite increasing basal LES pressure (P = 0.03), baclofen did not affect any of peristaltic parameters by primary or secondary peristalsis. Mosapride significantly decreased the threshold volume for triggering secondary peristalsis during rapid air distension (P = 0.04). Secondary peristalsis was triggered more frequently in response to rapid air distension after application of mosapride (P = 0.02). Mosapride significantly increased pressure wave amplitudes of secondary peristalsis during slow (P = 0.001) and rapid air distension (P = 0.002). Conclusions: Inhibition of baclofen on the triggering of secondary peristalsis presents during esophageal distension, indicating that sensory part of secondary peristalsis is probably mediated by the GABAB receptors. However, baclofen does not lead to any motility change in secondary peristalsis as induced by either slow or rapid air distension. Mosapride appears to enhance sensitivity to distension-induced secondary peristalsis and facilitates secondary peristaltic contractility, suggesting the involvement of 5-HT4 in the modulation of esophageal secondary peristalsis in humans.

Effects of mosapride on esophageal secondary peristalsis in humans

Secondary peristalsis is important for the clearance of refluxate or retained food bolus from the esophagus. Mosapride is a prokinetic agent that enhances GI motility by stimulating 5-hydroxytrypatamine(4) (5-HT(4) ) receptors, but its effects on secondary peristalsis are yet unclear in humans. We aimed to investigate the effect of a 5-HT(4) agonist mosapride on esophageal distension-induced secondary peristalsis in normal subjects. After a baseline recording esophageal motility, secondary peristalsis was generated by slow and rapid mid-esophageal injections of air in 15 healthy subjects. Two separate sessions with 40mg oral mosapride or placebo were randomly performed to test their effects on esophageal secondary peristalsis. Mosapride decreased the threshold volume for triggering secondary peristalsis during rapid air distension (4.5±0.3 vs 5.3±0.4mL; P=0.04) but not slow air distension (14.3±1.2 vs 13.3±1.3mL; P=0.41). Secondary peristalsis was triggered more frequently in response to rapid air distension after application of mosapride [100% (90-100%) vs 90% (80-100%); P=0.02]. Mosapride significantly increased pressure wave amplitudes of secondary peristalsis during slow (135.4±13.8 vs 105.0±12.9mmHg; P=0.001) and rapid air distensions (124.0±11.6 vs 95.9±14.0mmHg; P=0.002). Mosapride enhances sensitivity to distension-induced secondary peristalsis and facilitates secondary peristaltic contractility. These data provide an evidence for modulation of esophageal secondary peristalsis by the 5-HT(4) agonist mosapride, as well support for its clinical utility.

Control of esophageal distension-induced secondary peristalsis by the GABAB agonist baclofen in humans

Secondary peristalsis is important for the clearance of retained food bolus or refluxate from the esophagus. The effects of the gamma aminobutyric acid receptor type B (GABA(B) ) agonist on secondary peristalsis remain unclear in humans. We aimed to investigate the effect of a GABA(B) agonist baclofen on esophageal secondary peristalsis. After a baseline recording of esophageal motility, secondary peristalsis was generated by slow and rapid mid-esophageal injections of air in 15 healthy subjects. Two separate sessions with 40mg oral baclofen or placebo were randomly performed to test their effects on secondary peristalsis. Baclofen increased the threshold volume for triggering secondary peristalsis during slow air distension (P=0.003) and rapid air distension (P=0.002). Baclofen reduced the rate of secondary peristalsis by rapid air distension from 90% to 30% (P=0.0002). Baclofen increased basal lower esophageal sphincter pressure (P=0.03). Baclofen did not affect any of peristaltic parameters during primary or secondary peristalsis. This study provides an evidence for inhibitory modulation of esophageal secondary peristalsis by the GABA(B) agonist baclofen. Activation of secondary peristalsis is probably modulated by GABA(B) receptors; however, baclofen does not lead to any motility change in secondary peristalsis.

Effects of capsaicin-containing red pepper sauce suspension on esophageal secondary peristalsis in humans

Capsaicin-sensitive afferents have been implicated in the modulation of gastrointestinal sensorimotor functions. Secondary peristalsis is important for the clearance of retained refluxate or material from the esophagus. The aim of this study was to evaluate the effects of capsaicin-containing red pepper sauce suspension on esophageal secondary peristalsis in healthy adults. After a baseline recording of esophageal motility, secondary peristalsis was generated by slow and rapid mid-esophageal injections of air in 10 healthy subjects. Two separate sessions with saline and capsaicin-containing red pepper sauce were randomly performed to test their effects on esophageal secondary peristalsis. Infusion of capsaicin significantly increased pressure wave amplitude during rapid (P = 0.002) and slow air infusions (P = 0.01). After capsaicin, the threshold volume to generate secondary peristalsis was significantly decreased during rapid (P < 0.05) and slow air infusions (P = 0.02). Infusion of saline did not affect any parameters of secondary peristalsis during rapid or slow air infusion. The administration of capsaicin was accompanied by the occurrence of heartburn in all subjects. The acute administration of capsaicin-containing red pepper sauce suspension enhances sensitivity to distension-induced secondary peristalsis and facilitates secondary peristaltic contractility. These data suggest the involvement of capsaicin-sensitive afferents in the modulation of esophageal distension-induced secondary peristalsis in humans.

T1879 Mechanisms of Esophageal Distension-Induced Secondary Peristalsis in Humans: Studies With Capsaicin and Lidocaine

T1879 Mechanisms of Esophageal Distension-Induced Secondary Peristalsis in Humans: Studies With Capsaicin and Lidocaine