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Backgroud: The use of neuromodulators is prevalent in various functional gastrointestinal disease. However, data concerning the outcomes of these treatments in functional esophageal disorders (FED) remains limited and inadequate., Aims: The aim of the present study is to examine the efficacy of central neuromodulators in FED., Methods: We searched PubMed, EMBASE, and the Cochrane library databases from inception to April 2023. Randomized controlled trials that compared the effects of neuromodulators and placebos on FED are included. Primary outcome is the symptom improvement, and Rome IV criteria is used to assess eligible studies., Results: Eleven randomized controlled studies (three for functional chest pain, four for reflux hypersensitivity/functional heartburn, three for globus, and one for functional dysphagia) were included in the final analysis. Neuromodulators reduced chest pain by 52%-71% in patients with functional chest pain, and alleviated symptom by 46%-75% in patients with globus (n = 3, Odds ratio 6.30, 95% confidence interval 4.17-9.50). However, the results were inconsistent for reflux hypersensitivity and functional heartburn. There was a lack of convincing evidence to support the use of neuromodulators for functional dysphagia. The use of neuromodulators did not have a significant impact on the quality of life., Conclusions: Functional chest pain and globus may potentially benefit from the use of neuromodulators, but their effectiveness for functional dysphagia, functional heartburn and reflux hypersensitivity remains controversial. More controlled trials are needed to confirm the therapeutic effects on these conditions., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

The underlying causes of heartburn, characteristic symptom of gastroesophageal reflux disease (GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease (NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), and acid-sensing ion channel 3 (ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterized TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of patients with GERD. We studied 10 patients with NERD, 10 with erosive reflux disease (ERD), 7 with functional heartburn (FH), and 8 with Barrett's esophagus (BE). Biopsies obtained from the distal esophageal mucosa were costained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8 , and ASIC3 was assessed using qPCR. Patients with NERD had significantly increased expression of TRPV1 on superficial sensory nerves compared with ERD ( P = 0.028) or BE ( P = 0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in patients with NERD and ERD ( P ≤0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localization of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 coexpression on epithelial cells in NERD and ERD, suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in patients with NERD, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option. NEW & NOTEWORTHY We demonstrate for the first time that increased pain perception in patients with nonerosive reflux disease likely results from expression of acid-sensitive channels on superficial mucosal afferents and esophageal epithelial cells, raising the potential for topical therapy.

Background/aim: Esophageal acid sensitivity plays a role in symptomatic manifestation of gastroesophageal reflux disease (GERD). Esophageal hypomotility is common in patients with GERD. We aimed to determine whether esophageal acid sensitivity may differ between patients with and without esophageal hypomotility., Methods: We prospectively enrolled 41 consecutive patients (10 females, mean age 53 years, range 32-79) with typical reflux symptoms and 10 healthy subjects (5 females, mean age 45 years, range 28-56) for esophageal acid sensitivity and motility tests. Demographics, body mass index (BMI), and reflux symptoms using a validated questionnaire (GERDQ) were recorded. All subjects underwent infusion of 0.1 N hydrochloric acid in the esophagus at a rate of 10 mL/min for 10 minutes. The parameters for esophageal acid infusion included lag time, intensity rating, and acid sensitivity score., Results: Esophageal motility diagnosis included 24 patients with normal motility and 17 patients with ineffective esophageal motility (IEM). Lag time was similar between the patient groups. No differences between patients with normal motility and IEM were found for any of other acid infusion parameters. There was a positive correlation between lag time and BMI (r = .33, P = .04). GERDQ was negatively correlated to lag time (r = -.73, P < .001)., Conclusions: Esophageal acid sensitivity was similar in GERD patients with and without hypomotility. Decreased acid sensitivity in individuals with increasing body mass index may play a pathological role in symptomatic modulation of patients with GERD., (© 2019 John Wiley & Sons Ltd.)

Background and Aim: 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., Methods: Secondary peristalsis was performed with intra-esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1 N HCl following pretreatment with placebo or baclofen was randomly performed at least 1 week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol., Results: 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)., Conclusions: 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., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease (GERD)., Methods: Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicin-containing red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 mL of red pepper sauce diluted with 15 mL of saline and 20 mL of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL/min with a randomized and double-blind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli., Results: Infusion of capsaicin significantly increased heartburn perception in patients with GERD ( P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception ( P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis ( P = 0.001) and increased its frequency ( P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion ( P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis ( P = 0.002) and reduced the frequency of secondary peristalsis ( P = 0.02) during rapid air injection., Conclusion: Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

Objective: Acute 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., Methods: Secondary 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., Results: The 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., Conclusions: Esophageal 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.

Background/aim: Esophageal instillation of capsaicin or hydrochloric acid enhances secondary peristalsis. Our aim was to investigate whether intra-esophageal capsaicin infusion can influence symptom perception and physiological alteration of secondary peristalsis subsequent to acid infusion., Methods: Secondary peristalsis was induced by mid-esophagus injections of air in 18 healthy subjects. Two different sessions including esophageal infusion of hydrochloric acid (0.1 N) following pretreatment with saline or capsaicin-containing red pepper sauce were randomly performed at least one week apart. Symptoms of heartburn and secondary peristalsis were determined and compared between each study session., Results: The intensity of heartburn symptom subsequent to acid infusion was significantly reduced after capsaicin infusion as compared with saline infusion (54 ± 3 vs 61 ± 3; P = 0.03). Capsaicin infusion significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal acid infusion (8.0 ± 0.5 mL vs 4.4 ± 0.3 mL; P < 0.0001). The frequency of secondary peristalsis subsequent to acid infusion was significantly decreased after capsaicin infusion as compared to saline infusion (70% [60-82.5%] vs 80% [70-90%]; P = 0.03). Capsaicin infusion significantly decreased the pressure wave amplitude of secondary peristalsis subsequent to acid infusion during rapid air injections (90.6 ± 8.7 mmHg vs 111.1 ± 11.1 mmHg; P = 0.03)., Conclusions: Capsaicin appears to desensitize the esophagus to acid induced excitation of secondary peristalsis in humans, which is probably mediated by rapidly adapting mucosal mechanoreceptors. High capsaicin-containing diet might attenuate normal physiological response to abrupt acid reflux by inhibiting secondary peristalsis., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Secondary peristalsis contributes to clearance of retained refluxate or material from the esophagus., Aim: The goal of our study was to investigate the effects of hydrochloric acid (HCl) on physiological characteristics of esophageal secondary peristalsis in healthy adults., Methods: 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., Results: 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)., Conclusions: 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.

Background and Aim: Ineffective oesophageal motility (IOM) often occurs in patients with gastro-oesophageal reflux disease. We aimed to examine the hypothesis of whether the presence of IOM differs between patients with gastro-oesophageal reflux disease with different symptom profiles., Methods: Eligible patients were subclassified according to their predominant symptom of heartburn (HB) or acid regurgitation (AR). All patients underwent combined multichannel intraluminal impedance and oesophageal manometry. IOM was further graded according to the presence of oesophageal transit abnormalities., Results: Fourteen healthy individuals, 16 HB patients and 24 AR patients participated in this study. The percentage of swallows with complete bolus transit was lower in AR than in HB patients during liquid and viscous swallowing (P<0.05). Abnormal bolus transit occurred more frequently in AR patients than in HB patients with liquid swallows (P<0.001) and viscous swallows (P<0.05). IOM occurred more frequently in AR patients than in HB patients (42.7 vs. 12.5%, P=0.049). In patients with IOM, severe functional abnormality was more frequently found in AR patients than in HB patients (P<0.05)., Conclusion: This study suggests a potential link between oesophageal body dysfunction and individual reflux symptom. Patients with a predominant symptom of AR are characterized by greater IOM and defective bolus clearance.

Objective: This study aimed to compare the effect of intraluminal acidification on esophageal sensory perception and motor activity between older and younger patients with gastroesophageal reflux disease (GERD)., Material and Methods: All 40 subjects had saline and hydrochloric acid infused into the mid-esophagus. The esophageal perception to acid infusion was documented including lag time, intensity rating, and sensitivity score. Esophageal body motility was recorded., Results: The younger group had a shorter lag time to initial heartburn perception (p = 0.01) and a greater sensory intensity rating (p = 0.001). The acid infusion sensitivity score was lower in the older patients (p = 0.001). Age positively correlated to lag time to initial symptom perception (r = 0.44, p = 0.005), but negatively correlated to sensory intensity (r = -0.40, p = 0.01) and acid infusion sensitivity score (r = -0.39, p = 0.01). When compared with saline infusion, acid infusion induced a significant increase in the deglutition frequency in younger patients (0.51 vs. 0.67, p = 0.005), but not in older patients (0.59 vs. 0.65, p = 0.67)., Conclusions: Age-related decrease in sensorimotor response to esophageal acidification may be an important element in the pathogenesis and clinical presentation of GERD in older adults.

Background: This study was to determine whether patients with significant nighttime heartburn had more disturbed sleep and more gastroesophageal acid reflux than those without significant nighttime heartburn., Methods: Thirty-three reflux patients were stratified into 2 groups (nighttime heartburn, without nighttime heartburn). All patients completed questionnaires assessing daytime and nighttime heartburn and subjective sleep by Pittsburgh Sleep Quality Index. All participants underwent 24-hour esophageal pH monitoring and an overnight polysomnographic study., Results: The number of reflux events longer than 5 minutes was significantly greater in patients with nighttime heartburn than in those without nighttime heartburn for the total (P=0.004) and upright (P=0.01) position periods. Acid contact time was significantly greater in patients with nighttime heartburn during the upright (P=0.003) period and during the total (P=0.001) period. Patients with nighttime heartburn reported significantly greater subjective sleep impairment (8.1+/-0.7) than those without nighttime heartburn (6.1+/-0.4; P=0.02), but no difference could be observed in any objective sleep parameter by an overnight polysomnographic study between the groups., Conclusions: Patients with significant nighttime heartburn seem to have more acid reflux compared with those without nighttime heartburn. Nighttime heartburn together with sleep complaints is associated with excessive gastroesophageal reflux.

Background and Aim: Studies have shown that altered visceral perception and lower pain thresholds in patients with symptomatic gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Autonomic changes associated with the perception of heartburn in patients with GERD are poorly understood., Methods: A total of 12 GERD patients (six male, six female; mean age 37.2 +/- 2.7 years) and 12 controls (five male, seven female; mean age 32.8 +/- 2.2 years) were studied. The study protocol included a 20-min water infusion (6 mL/min), and 20-min acid infusion (0.1 N HCl, 6 mL/min). Spectral analysis of heart-rate variability (HRV) was used to assess autonomic functioning. The measured HRV indices included the power in the low-frequency (LF) band (0.04-0.15 Hz) reflecting sympathetic tone, and power in the high-frequency (HF) band (0.15-0.5 Hz) reflecting vagal tone, and the LF/HF ratio as an indicator of sympathovagal balance., Results: The GERD group experienced more heartburn than controls with acid infusion. Between-group comparisons showed no significant changes in LF band power in any period. The HF band power was significantly lower in GERD patients during all infusion periods. The LF/HF ratio was significantly larger in GERD patients., Conclusions: The perception of heartburn induced by esophageal acid infusion is associated with a simultaneous increase in sympathetic modulation in patients with GERD. The autonomic responses with esophageal acid infusion are significantly different between healthy subjects and GERD patients., (Copyright 2004 Blackwell Publishing Asia Pty Ltd)

Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined. [ABSTRACT FROM AUTHOR]

Background: Ineffective esophageal motility (IEM) is the most common motility disorder. However, little is known about its pathophysiology. Vagal afferent nerves convey esophageal intraluminal bolus information to solitary nucleus, which is likely to be involved with esophageal primary and secondary peristalsis (SP). We hypothesized that altered mucosal sensory afferents underlie the pathogenesis of IEM. Methods: We prospectively collected esophageal biopsies from 38 patients with proton pump inhibitor‐refractory reflux symptoms from January to December 2019. All patients underwent high‐resolution manometry for the evaluation of primary and secondary peristalsis, and off‐PPI 24‐h impedance‐pH studies. Biopsies were analyzed using immunohistochemistry for identification of calcitonin gene‐related peptide‐immunoreactive (CGRP‐IR) nerves and qPCR for mRNA expression of potential mechanoreceptors. Key Results: Overall 32 patients were finally analyzed which consisted of 11 patients with normal motility and 21 patients with IEM. The position of mucosal CGRP‐IR nerves from the esophageal lumen did not differ between the two groups (the proximal esophagus (p = 0.52), the mid‐esophagus (p = 0.92), the distal esophagus (p = 0.29)) with the similar reflux profile. No difference was seen in the position of CGRP‐IR nerves between patients with successful triggering of SP and those unable to trigger SP. There was also no difference in mRNA expression of each potential mechanoreceptors (TRPA1, TRPV1, TRPV4, ASIC1, ASIC3) between the two groups. Conclusions and Inferences: Our study showed that mucosal sensory afferents nerve position and mRNA expression of potential mechanoreceptors did not correlate to weak esophageal contraction. [ABSTRACT FROM AUTHOR]

Background and Aim: Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms. Methods: This study enrolled 303 consecutive patients with proton pump inhibitor treatment‐naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non‐dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances. Results: There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms. Conclusions: Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms. [ABSTRACT FROM AUTHOR]

Background and Aim: 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. Methods: Secondary peristalsis was performed with intra‐esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1 N HCl following pretreatment with placebo or baclofen was randomly performed at least 1 week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background and Aim Esophageal infusion of capsaicin-containing red pepper sauce induced heartburn symptoms in patients with gastroesophageal reflux disease (GERD). We aimed to test the hypothesis whether sleep disturbance modulates esophageal sensitivity to capsaicin infusion in patients with GERD. Methods We enrolled 40 patients with their sleep quality measured by the Pittsburg Sleep Quality Index with > 5 indicating sleep disturbance. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score by esophageal infusion of capsaicin-containing red pepper sauce. Objective sleep measures were assessed by ambulatory actigraphy. Results We found 22 patients with sleep disturbance. The patients with sleep disturbance had shorter lag time to initial heartburn perception ( P = 0.03) and greater sensory intensity rating ( P = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance ( P = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency ( P = 0.04), longer average awakening time ( P = 0.03), and greater total activity account ( P = 0.04). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time ( r = 0.43, P = 0.03). Conclusions We have shown that GERD patients with sleep disturbance have significantly enhanced heartburn perception to capsaicin infusion as compared with those with normal sleep. Our findings suggest that sleep disturbance is associated with esophageal hypersensitivity to capsaicin infusion in patients with GERD. [ABSTRACT FROM AUTHOR]

Background and Aim We aimed to evaluate whether acute esophageal instillation of capsaicin and hydrochloric acid had different effects on distension-induced secondary peristalsis. Methods 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). Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Abstract: This review addresses current advances in gastroesophageal reflux disease (GERD) and its influence on sleep and health-related quality of life (QOL). Sleep difficulties are highly prevalent among adults with GERD, especially those who experience nighttime symptoms. These sleep difficulties result in substantial costs to the health care system by increasing provider visits. Because continued sleep disruption leads to increased daytime sleepiness and fatigue, nocturnal heartburn can reduce work productivity, as well as reduce function when performing normal daily activities. The continued presence of nocturnal symptoms in routine medical treatment is strongly associated with decreases in health-related quality of life. There is a greater loss of productivity to the employer and poorer health-related QOL (HRQOL) for the patient. Obstructive sleep apnea syndrome and obesity seem to predispose some patients to nocturnal GERD, and the presence of either of these conditions may help to identify patients with symptoms consistent with GERD. Appropriate management of GERD must include treatment of nighttime reflux symptoms that affect difficulty in both initiating and maintaining sleep. [Copyright &y& Elsevier]

Background: Recurrence of gastroesophageal reflux disease (GERD) is common among patients who are no longer receiving proton pump inhibitors (PPIs). This study investigated factors associated with GERD recurrence. Methods: We included 499 consecutive GERD patients who completed validated reflux and psychological questionnaires before undergoing upper endoscopy. All patients were treated with PPIs and followed up. Results: Recurrence was observed in 89 (30.4%) of 293 patients during the 1-year follow up. Patients with recurrence had a higher prevalence of diabetes mellitus (p = 0.037), higher baseline GERD Questionnaire (GERDQ) scores (p = 0.002), and higher Pittsburgh Sleep Quality Index scores (p = 0.045). Log-rank analysis showed that a GERDQ score of ⩾8 was independently associated with an increased recurrence risk (p = 0.002). The scores of all psychological questionnaires and health-related quality of life questionnaire worsened more at the end of follow up in patients with recurrence than in those without recurrence. Multivariate analysis revealed that a higher GERDQ score was the only independent risk factor for GERD recurrence (p = 0.024). GERD patients who have greater initial symptom burden will have a higher recurrence rate after discontinuing PPIs. Conclusions: GERD patients with greater initial symptom burden are more likely to have recurrence after discontinuing PPIs. This study highlights the importance of developing a new strategy to prevent GERD recurrence in the management of this common disorder. [ABSTRACT FROM AUTHOR]