Esophageal Electrical Stimulation Research Articles

Comparison of brain injuries in rat cardiac arrest models induced by asphyxia and electrical stimulation

To compare the severity of brain injury between asphyxia and electrical stimulation induced cardiac arrest in rats. Forty-two healthy male Sprague-Dawley (SD) rats were randomized into sham group (n = 6), asphyxia group (n = 18) and electrical stimulation group (n = 18). Rats in each group were given invasive mechanical ventilation and femoral blood vessels catheterization for monitoring blood pressure and fluid infusion. In the asphyxia group, the tracheal tube was clamped to induce cardiac arrest, and in the electrical stimulation group, the esophageal electrical stimulation was used to induce cardiac arrest, and cardiopulmonary resuscitation (CPR) was performed 4 minutes after cardiac arrest. In the sham group, only tracheal intubation and femoral artery intubation were performed after anesthesia, but cardiac arrest was not induced. Animals were allowed to survive until 72 hours after resuscitation, and survival analysis was performed using Kaplan-Meier curves. At 24 hours and 72 hours after resuscitation, the neurological deficit score (NDS) was measured. The vena cava blood was collected, and the brain injury associated serum biomarkers, neuron-specific enolase (NSE) and S100B, were detected by enzyme-linked immunosorbent assay (ELISA). The brain tissues were then harvested to perform hematoxylin-eosin (HE) staining for observing pathological changes in the hippocampal CA1 area with light microscopy. Cardiac arrest was successfully induced in both the asphyxia group and the electrical stimulation group, 94.4% (17/18) and 88.9% (16/18) animals were resuscitated successfully in the two groups respectively. Kaplan-Meier curves analysis showed that 72-hour cumulative survival rate was similar in the asphyxia group and the electrical stimulation group (Log-Rank test: χ2 = 0.040, P = 0.841). Both asphyxia group and electrical stimulation group had higher NDS score than sham group at 24 hours after resuscitation (37.50±4.26, 32.17±4.02 vs. 8.33±2.33, both P < 0.01). NDS score showed a downwards trend at 72 hours after resuscitation in both model groups, and the decline was more significant in the electrical stimulation group, which was significantly different as compared with asphyxia group (14.00±2.89 vs. 26.33±4.84, P < 0.05). ELISA results showed that the levels of serum NSE at 24 hours after resuscitation in the asphyxia and electrical stimulation groups were significantly higher than those in the sham group (μg/L: 1.02±0.07, 1.02±0.02 vs. 0.87±0.02, both P < 0.05). NSE kept increasing at 72 hours after resuscitation in the asphyxia group, which showed significant difference as compared with sham group (μg/L: 1.03±0.05 vs. 0.87±0.02, P < 0.01). But it had almost recovered to the normal level in the electrical stimulation group without significant difference as compared with sham group (μg/L: 0.96±0.04 vs. 0.87±0.02, P > 0.05). There was no significant difference in S100B level at different time points after resuscitation among three groups. It was displayed under light microscope that there was no significant neuronal damage in the hippocampal CA1 area in the two model groups at 24 hours after resuscitation as compared with the sham group. At 72 hours, there were certain damages in the hippocampal CA1 area in both model groups, which were more obvious in the asphyxia group. Both cardiac arrest models induced by asphyxia and electrical stimulation show a certain degree of brain injuries after resuscitation. Brain injuries are more severe in asphyxia-induced cardiac arrest compared with trans-esophageal electrical stimulation method.

Electrical lower esophageal sphincter augmentation in patients with GERD and severe ineffective esophageal motility\u2014a safety and efficacy study

BackgroundLaparoscopic fundoplication (LF), even if performed in specialized centers, can be followed by long-term side effects such as dysphagia, gas bloating or inability to belch. Patients with an ineffective esophageal motility (IEM) and concurrent GERD are prone to postoperative dysphagia after LF. The aim of this study is to evaluate the safety and efficacy of electrical lower esophageal sphincter stimulation in patients with IEM and GERD.MethodsThis is a prospective, open-label single center study. Patients with PPI-refractory GERD and ineffective esophageal motility were included for lower esophageal sphincter electrical stimulation (LES-EST). Patients underwent prospective follow-up including physical examination, interrogation of the device and were surveyed for changes in the health-related quality of life score.ResultsAccording to power analysis, 17 patients were included in this study. Median distal contractile integral (DCI) was 64 mmHg s cm (quartiles 11.5–301). Median total % pH < 4 was 8.9 (quartiles 4–21.6). Twelve patients (70.6%) underwent additional hiatal repair. At 1-month follow-up, none of the patients showed any clinical or radiological signs of dysphagia. There were no procedure related severe adverse events. Mean total HQRL improved from baseline 37.53 (SD 15.07) to 10.93 (SD 9.18) at follow-up (FUP) (mean difference 24.0 CI 15.93–32.07) p < 0.001.ConclusionsLES-EST was introduced as a potential technique to avoid side effects of LF. LES-EST significantly improved health related quality of life and does not impair swallowing in patients with GERD and ineffective esophageal motility.

Argon: a novel therapeutic option to treat neuronal ischemia and reperfusion injuries?

Neuronal injury and neuroprotection: Ischemia and reperfusion injuries in neuronal cells such as acute ischemic stroke - represent the third leading cause of death in the world. Current therapeutic concepts mainly aim to re-establish cerebral blood flow within a time window of less than 3 hours with the goal of limiting secondary brain injury. Secondary brain injury of the “penumbra” develops exponentially, causing severe mental and physical disabilities. The resulting morbidity and mortality in patients of all ages leads to an enormous economic burden. Neurons are well-known to possess a limited potential to recover and regenerate their basic function once damaged. Therefore the protection and especially the therapy of neuronal injuries in cells and organ systems has emerged as a major focus of research in recent years. The aim is to maximize neuronal function not only by restoring sufficient blood flow to the areas at risk, but also by protecting neuronal cells with various novel interventions. Many of these interventions, such as intravascular cooling, focus on the reduction of neuronal metabolism in an effort to induce protection.

PWE-046 The development of human esophageal pain hypersensitivity is associated with anxiety and sympathetic nervous system activation

IntroductionExperimental acid infusion in the distal oesophagus leads to secondary hyperalgesia in the proximal oesophagus in most healthy subjects but 30% remain resistant. The factors that mediate differences in sensitisation...

Randomised clinical trial: pregabalin attenuates the development of acid‐induced oesophageal hypersensitivity in healthy volunteers – a placebo‐controlled study

Acid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown. To study the effects of pregabalin on development of secondary oesophageal hypersensitivity in healthy humans. Placebo-controlled, double-blind, randomised, cross-over study of 15 healthy volunteers (six women, age 21-56 years). After oesophageal manometry, baseline pain thresholds (PTs) to proximal oesophageal electrical stimulation were determined using bipolar ring electrodes. A 30-min infusion of HCl was performed in the distal oesophagus followed by PT measurements at 30 and 90 min. This protocol was repeated after administration of pregabalin (dosing schedule: 75 mg twice daily for 3 days then 150 mg twice daily for 1 day and then 150 mg on the morning of study) or placebo. T0 PTs were similar in patients after receiving placebo or pregabalin [mean (s.d.) 32.9 mA (20.5) vs. 34.1 (15.7), P = 0.42]. Pregabalin reduced development of acid-induced hypersensitivity in the proximal oesophagus at 30 min [mean change in PT (C.I.) placebo -6.2 mA (-11.3 to +1.3) vs. pregabalin +0.20 mA (-2.7 to +3.3)] and 90 min [placebo -3.7 mA (-10.0 to +2.0) vs. pregabalin +0.7 mA (-4.7 to 7.3)] overall P = 0.001. Pregabalin reduced median visual analogue scale score for acid-induced pain (1/10 vs. placebo 3/10, P = 0.027). Pregabalin attenuates development of secondary hypersensitivity in the proximal oesophagus after distal oesophageal acidification; it may thus have a role in treatment of patients with proven oesophageal pain hypersensitivity.

Effects of Isolated Hyperinsulinaemia on Sensory Function in Healthy Adults

Gastrointestinal symptoms such as pain, bloating, nausea and vomiting are more frequent in pre-diabetic states as well as established diabetes, compared to healthy individuals. The mechanisms behind these symptoms are multi-factorial and complex. Furthermore, the effect of isolated hyperinsulinaemia on visceral and peripheral sensory function is poorly understood. Thus, the current study aimed to evaluate effects of acute hyperinsulinaemia on sensory function in healthy adults. The sensitivity to electrical oesophageal and median nerve stimulation was assessed in 15 healthy volunteers together with recording of evoked brain potentials. All subjects were studied both fasting and using a euglycaemic hyperinsulinaemic clamp. There was on average a 15% increased sensitivity to oesophageal electrical stimulation during hyperinsulinaemia compared to fasting state (P<0.05), but the sensation after median nerve stimulation remained stable (P=0.58). No significant changes in latencies and amplitudes of evoked brain potentials were observed after oesophageal or median nerve stimulation (all P>0.05). This study suggests that acute isolated hyperinsulinaemia increases visceral sensitivity, but does not influence the somatic sensory function. The lack of changes in the evoked brain potentials may indicate that hyperinsulinaemia affects the visceral sensory system at a peripheral level. Our result suggests distinct functions of insulin in the various parts of the nervous system, and yields further clues to the significance of insulin as a satiety signal.

Effect of Autonomic Modulation on Human Esophageal Pain Hypersensitivity

Introduction Patients with Functional Gastrointestinal Disorders (FGID) often display persistent and heightened pain sensitivity to experimental gut stimulation, a phenomenon known as Visceral Pain Hypersensitivity (VPH). Current management of pain in FGID involves the use of either antispasmodics or antidepressants; both are often unsatisfactory. The role of the autonomic nervous system (ANS) in modulating pain is well known; however, the effect of ANS modulation on VPH has not been studied. Methods The aim was to determine whether physiological modulation of the Autonomic Nervous System (ANS) influences the degree of oeosophageal VPH in healthy volunteers using a validated model.10 healthy volunteers (avr age 30.5 years; 8 male, 6 w-British) underwent psychological profiling for stress, anxiety and personality type. Study 1 : Pain thresholds to proximal and distal oesophageal electrical stimulation were measured. Thereafter the subjects underwent hydrochloric acid infusion (0.15 M) in the distal oesophagus for 30 min. This was followed by measurements of oesophageal pain threshold (using visual analogue scales) to electrical stimulation in the proximal, unexposed oesophagus at 30, 60 and 90 min. Study 2 was performed at an interval of 2 weeks and the protocol was identical to that of study 1 except that during the acid infusion cardiac vagal tone(CVT) was increased by deep breathing at full inspiratory capacity in 4 sec followed by forced expiratory vital capacity in 6 sec at a frequency of 0.1 Hz (6 breaths/minute, over 5 min). ANS was monitored throughout in both studies. Results The majority of volunteers were ‘agreeable extroverts’, which are protective personality factors. There was only 10% depression and 20% anxiety, showing our exclusion criteria effective. 70% of the subjects rated significant for alexithymia and showed a weak non-significant correlation with the level of sensitisation to acid (r = 0.49 p = 0.14). In study 1 in comparison to baseline, we observed a reduction in CVT during acid exposure while in study 2 the CVT increased during acid exposure, that is, (study 1 difference of -0.09 vs baseline; study 2 difference of 4.93 vs baseline) (p = 0.006). In study 2, all 10 volunteers reduced their level of oesophageal sensitisation to acid in comparison to study 1 with 50% failing to sensitise completely. Overall there was a reduction in sensitisation of 16 mA between study 1 and 2 (p = 0.004). Conclusion This preliminary study suggests that the parasympathetic nervous system has anti-hyperalgesic properties in human oesophageal VPH. This data points to a possible change in the way we treat visceral pain, highlighting likely new targets for the development of novel treatments. Further research is now required with a powered study focusing on exploring mechanism of desensitisation during deep breathing.

Effect of autonomic modulation on human oesophageal pain hypersensitivity

<h3>Introduction</h3> Patients with Functional Gastrointestinal Disorders (FGID) often display persistent and heightened pain sensitivity to experimental gut stimulation, a phenomenon known as Visceral Pain Hypersensitivity (VPH). Current management of pain in FGID involves the use of either antispasmodics or antidepressants; both are often unsatisfactory. The role of the autonomic nervous system (ANS) in modulating pain is well known; however, the effect of ANS modulation on VPH has not been studied. <h3>Methods</h3> The aim was to determine whether physiological modulation of the Autonomic Nervous System (ANS) influences the degree of oeosophageal VPH in healthy volunteers using a validated model.10 healthy volunteers (avr age 30.5 years; 8 male, 6 w-British) underwent psychological profiling for stress, anxiety and personality type. <i>Study 1</i>: Pain thresholds to proximal and distal oesophageal electrical stimulation were measured. Thereafter the subjects underwent hydrochloric acid infusion (0.15 M) in the distal oesophagus for 30 min. This was followed by measurements of oesophageal pain threshold (using visual analogue scales) to electrical stimulation in the proximal, unexposed oesophagus at 30, 60 and 90 min. Study 2 was performed at an interval of 2 weeks and the protocol was identical to that of study 1 except that during the acid infusion cardiac vagal tone(CVT) was increased by deep breathing at full inspiratory capacity in 4 sec followed by forced expiratory vital capacity in 6 sec at a frequency of 0.1 Hz (6 breaths/minute, over 5 min). ANS was monitored throughout in both studies. <h3>Results</h3> The majority of volunteers were ‘agreeable extroverts’, which are protective personality factors. There was only 10% depression and 20% anxiety, showing our exclusion criteria effective. 70% of the subjects rated significant for alexithymia and showed a weak non-significant correlation with the level of sensitisation to acid (r = 0.49 p = 0.14). In study 1 in comparison to baseline, we observed a reduction in CVT during acid exposure while in study 2 the CVT increased during acid exposure, that is, (study 1 difference of -0.09 vs baseline; study 2 difference of 4.93 vs baseline) (p = 0.006). In study 2, all 10 volunteers reduced their level of oesophageal sensitisation to acid in comparison to study 1 with 50% failing to sensitise completely. Overall there was a reduction in sensitisation of 16 mA between study 1 and 2 (p = 0.004). <h3>Conclusion</h3> This preliminary study suggests that the parasympathetic nervous system has anti-hyperalgesic properties in human oesophageal VPH. This data points to a possible change in the way we treat visceral pain, highlighting likely new targets for the development of novel treatments. Further research is now required with a powered study focusing on exploring mechanism of desensitisation during deep breathing.

Different effects of morphine and oxycodone in experimentally evoked hyperalgesia: a human translational study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Previous studies using short-lasting experimental pain stimulations in healthy volunteers have shown differences in opioid effects regarding visceral pain stimulations. However, these differences can be more pronounced in patients due to a sensitized pain system. Therefore, the aim of the present study was to mimic the clinical situation by investigating opioid effects on experimental pain in healthy volunteers after experimentally evoked hyperalgesia. WHAT THIS STUDY ADDS? * We now know that morphine and oxycodone exerts different effects in the sensitized pain system as we found a greater analgesic effect of oxycodone in response to skin, muscle and oesophageal pain stimulation. This supports clinicians' experiences that oxycodone can be superior to morphine in the treatment of some pain conditions. The evoked hyperalgesia bridged findings from studies in healthy volunteers to patients, and new fundamental knowledge on different analgesic effects in hyperalgesia was found. AIM Similar analgesics may have different analgesic potencies especially in patients in whom the pain system is sensitized. The aim was to investigate different opioid effects on experimental pain after the sensitized pain system was mimicked evoking hyperalgesia in healthy volunteers. METHODS Twenty-four healthy volunteers were randomized to treatment with morphine (30 mg orally) and oxycodone (15 mg orally) or placebo in a double-blind crossover study. Hyperalgesia was induced by oesophageal perfusion with acid and capsaicin. Several exploratory endpoints were studied using skin heat, muscle pressure and oesophageal mechanical, heat and electrical stimulation. Effects on pain from deeper structures were considered most important. RESULTS Different analgesic potencies were found. Oxycodone had a greater analgesic effect than morphine attenuating pain from: (i) heat stimulation of skin (P= 0.016); difference between the means of 0.39 degrees C, 95% CI 0.22, 2.09. (ii) muscle pressure (P < 0.001); difference between the means of 11.93kPa, 95% CI 5.4, 18.5. (iii) oesophageal heat stimulation (P < 0.001); difference between the means of 38.54 cm(2), 95% CI 15.37, 61.71 and (iv) oesophageal electrical stimulation (P= 0.016); difference between the means of 6.69mA, 95% CI 1.23, 12.13. CONCLUSION After sensitization of the pain system different analgesic potencies of morphine and oxycodone were found in response to skin, muscle and oesophageal pain stimulation, in which oxycodone had a greater effect. As similar differential analgesic potencies of the two opioids have been found in patients with chronic pain, the experimental hyperalgesia model bridged findings from studies in healthy volunteers to patients.

OC-061 Acid-induced oesophageal hypersensitivity is inhibited by pregabalin treatment: Abstract OC-061

Introduction Oesophageal acid infusion in humans induces primary and secondary hyperalgesia due to peripheral and central sensitisation, respectively.1 Pregabalin is a centrally acting modulator of voltage-sensitive calcium channels which reduces neuropathic pain by attenuating the release of multiple neurotransmitters2 in the CNS. Its efficacy in reducing acid-induced oesophageal hypersensitivity has not been explored. Methods Single-centre, placebo-controlled, double-blind, randomised, two-period, cross-over study of 15 healthy volunteers (21–52 years, 9 males) attending on three visits. On visit 1, after oesophageal manometry, pain thresholds (PTs) to oesophageal electrical stimulation were determined using bipolar ring electrodes positioned in the proximal and distal oesophagus. Thereafter, a 30 min infusion of HCL was performed in the distal oesophagus. PT was measured again at both sites at 30 and 90 min after the acid infusion. The same methods were repeated for three visits. Participants were then given either pregabalin or placebo after visits 1 and 2. The intervals were at least; 1 week between visits 1 and 2, and 2 weeks between visits 2 and 3 (to allow time for drug washout). The dose of pregabalin used was 75 mg bd for 3 days, 150 mg bd for 1 day and 150 mg od. Results The median decrease in PT at 30 min after acid, compared to baseline in the proximal oesophagus was significantly less after treatment with pregabalin. This pattern was maintained even at 90 min after acid, but to a lesser degree (Abstract 061). The subjective score of pain to acid infusion was also reduced while on placebo compared to pregabalin (VAS median of 3 vs 1, p=0.0270). The baseline PTs before acid infusion at placebo and pregabalin visits were not significantly different (p=0.42). There were no differences in the change in post-acid PT between pregabalin and placebo in the distal oesophagus. Conclusion Pregabalin prevents the development of secondary hyperalgesia in the proximal oesophagus after distal oesophageal acidification, both on objective and subjective assessments of pain. It has no significant effect on the site of acid exposure, indicating that it acts to reduce central sensitisation and is not analgesic. Studies of pregabalin in patients with acid-induced oesophageal hypersensitivity are warranted.

Evidence for oesophageal visceral hypersensitivity and aberrant symptom referral in patients with globus

We tested the hypotheses that globus patients demonstrate oesophageal visceral hypersensitivity and aberrant viscerosomatic referral of oesophageal stimuli. Oesophageal visceral perception was assessed by oesophageal balloon distension and electrical stimulation in nine patients with globus and compared with 11 healthy controls. Oesophageal perception and pain thresholds were determined. Subjects recorded the area of thoracic viscerosomatic referral on a body map in response to each stimulus. All the patients reported their first sensation at balloon volumes between 2 and 6 mL whereas controls reported their first sensation at volumes between 3 and 14 mL (P = 0.03). All the patients reported pain at balloon volumes between 5 and 12 mL whereas controls experienced pain at volumes between 8 and 20 mL (P = 0.001). In response to electrical stimulation to the oesophagus patients and controls demonstrated comparable sensory thresholds. In response to oesophageal balloon distension seven of nine patients, but no controls, referred the sensation to the region at or above the suprasternal notch (P = 0.001). Similarly, significant differences in viscerosomatic referral pattern were observed in response to oesophageal electrical stimulation (P = 0.03). Patients with globus demonstrate oesophageal visceral hypersensitivity to mechanical distension. The differential responses to stretch and electrical stimuli may indicate that the hypersensitivity is a peripheral, rather than central, phenomenon. The aberrant referral of oesophageal sensations in response to both mechanical and electrical stimulation supports the hypothesis that referral of symptoms to the neck might be a central phenomenon.

Optimal Electrical Stimulation Modality for Cortical Esophageal Evoked Potentials: Transmural or Intraesophageal?

Esophageal electrical stimulation using short and a relatively small number of (200 micros, 0.2 Hz, n = 25) electrical pulses generates a characteristic and well defined cortical evoked potential response (EP). There are two methods of stimulation: either through intraesophageal electrodes or with transmural electrodes. The objective of this paper is to compare EP response, sensations and heart rate variability power spectra elicited by both stimulation modalities in healthy volunteers. Our results suggest that transmural stimulation is more accurately perceived and at lower intensities, produces more reproducible peaks of higher amplitude than during intraesophageal stimulation. During either mode of esophageal stimulation, power within the high-frequency component of the heart rate variability power spectrum is enhanced.

Cortical evoked responses (CEP) to esophageal electrical stimulation before, and after, acid sensitization of viscero-afferent neural pathways

Cortical evoked responses (CEP) to esophageal electrical stimulation before, and after, acid sensitization of viscero-afferent neural pathways

Visceral perception and psychoneurotic tendency relate to cerebral evoked potentials by esophageal electrical stimulation

Visceral perception and psychoneurotic tendency relate to cerebral evoked potentials by esophageal electrical stimulation

Visceral perception and psychoneurotic tendency relate to cerebral evoked potentials by esophageal electrical stimulation

Visceral perception and psychoneurotic tendency relate to cerebral evoked potentials by esophageal electrical stimulation

Objective assessment of cognitive factors involved in visceral perception by using event-related cerebral evoked responses to esophageal target stimulation in man.

Evoked potential (EP) studies provide an objective measure of the neural pathways involved with perception of gastrointestinal stimulation. The effects of cognitive factors, such as anticipation or awareness, on EP responses are not known. We compared the EP response to esophageal electrical stimulation with the cortical activity associated with target detection and anticipation of the same stimulus. In 12 healthy men (26.8+/-6 years old), esophageal electrical stimulation (0.2 Hz, 0.2 msec, 15 mA) was applied, and the EP recorded using scalp electrodes. A computerized model of randomly applied target stimuli (1:5 ratio) was used to separately record the EP associated with stimulation and the event-related cognitive EP associated with a dual task-related or anticipated stimulation approach. A periodic electrical stimulus represented the nontarget stimulus and a second electrical impulse (oddball model) or an omitted stimulus (anticipatory model) the target stimulus. The event-related cognitive EP responses were also compared with standard and anticipatory auditory P300 evoked potentials. The esophageal and auditory oddball stimulus approach elicited event-related P300EP in all subjects. P300EP associated with electrical stimulation had a longer peak latency (P < 0.0001) and smaller amplitude than those obtained with auditory stimulation. Anticipatory evoked potentials could be obtained by electrical skipped stimulation in 8 of 12 subjects. These EP were similar to those obtained with omitted auditory target stimulation, although of significantly smaller amplitude than auditory standard P300EP (P < 0.001). In conclusion, the brain response associated with directed effortful processing of discriminate esophageal stimuli consists of a large event-related potential (P300EP). Anticipatory stimulation produces a similar event-related cortical response, which is associated with attention to and awareness of the actual stimulus. The P300EP to gastrointestinal stimuli may provide an objective and powerful electrophysiological tool for the assessment of the cognitive factors associated with visceral perception.

Abnormal visceral perception in patients with functional dyspepsia: use of cerebral potentials evoked by electrical stimulation of the oesophagus.

Altered visceral perception is thought to be included in the pathogenesis of functional dyspepsia. However, in previous studies, the assessment of visceral perception has been based solely on patients self-reported symptoms. Cerebral evoked potential (EP), either by mechanical or electrical stimulation (ES) of the visceral organ, is used to evaluate visceral perception via afferent neural pathways. In this study, we investigated the visceral perception in patients with functional dyspepsia by EP to eliminate the possibility of self-reported bias. EP responses were recorded by oesophageal ES at 37 cm from the nostril in 14 patients with functional dyspepsia and 14 normal healthy control subjects. Threshold levels of perception, peak latencies and peak-to-peak amplitudes of EP were evaluated. There was no difference in the sensory threshold between the dyspeptic patients and the control subjects (median 6 mA, range 2-12 mA, vs. 8 mA, range 6-14 mA; P= 0.09). There was a strong trend towards a decreased discomfort threshold in the patients when compared to the control subjects (median 14 mA, range 6-24 mA vs. 20 mA, range 14-26 mA; P = 0.05). The latency of the later EP peak (N2) among the patients (154 ¿ 4 ms) was significantly shorter than that of the control subjects (171 ¿ 3 ms, P < 0.01) although there was no difference between the earlier peaks (Ni and P1). There was also no difference in the amplitudes (Ni/Pi and P1/N2) of EP between the patients and the control subjects. Half of the patients (seven out of 14) complained of nausea during ES but the control subjects were unaffected. The latency of the first EP peak (Ni) in the patients with nausea was significantly shorter (66 ¿ 3 ms) than that of the patients without nausea (79 ¿ 4 ms, P 0.05) or among the control subjects (80 ¿ 3 ms, P < 0.05). These results suggest that dyspeptic patients may recruit a greater number of fast conducting myelinated nerve fibres that convey visceral afferent impulses to the brain and/or that dyspeptic patients may have an altered central processing of the visceral perception. We conclude that EP recording by oesophageal ES provides an objective measurement of altered visceral perception in patients with functional dyspepsia.

Effects of esophageal stimulation in healthy subjects.

We studied the effects of esophageal electrical stimulation on heart rate variability power spectra (PS/HRV) and cortical evoked potentials (EPs) in healthy subjects. The intensity of stimulation was varied from 2.7 to 20 mA. We found that the amplitude of the cortical evoked potentials (amplitude of the N2/P2 peak) increased from 5.1 +/- 0.7 microV at 5 mA to 16.3 +/- 1.1 microV at 20 mA. The PS/HRV showed an increase in the vagal modulation of the sinus node. When the stimulation frequency was varied from 0.1 to 1 Hz at a constant intensity of 15 mA, the amplitude of cortical EPs (N2/P2 peak) decreased with increase in the frequency of stimulation (p < 0.05). The LF:HF ratio decreased significantly for all frequencies of stimulation (p < 0.005). An experimental paradigm to evoke the cognitive component in the cortical EPs yielded a peak around 354 ms following the stimulus.

Effects of esophageal stimulation in patients with functional disorders of the gastrointestinal tract.

We studied the effects of esophageal electrical stimulation on cortical-evoked potentials (EPs) and power spectrum of heart rate variability (PS/HRV) in patients with diabetes and non-cardiac chest pain (NCCP). We also recorded cognitive-evoked potentials (P300 EPs) in response to an odd-ball stimulation in patients with NCCP. Diabetic patients did not yield reproducible cortical EPs. Their power spectra of heart rate variability (PS/HRV) showed an increased vagal modulation during stimulation. In patients with NCCP the P300 EPs were of greater amplitude (17 +/- 3 microV vs. 12 +/- 1 microV in controls, p < 0.04), while peak latencies were slightly elongated in patients (382 +/- 22 ms vs. 354 +/- 12 ms in controls). The PS/HRV in these patients also showed an increased vagal modulation of the sinus node activity. Our results suggest the following: (1) in patients with diabetes, afferent pathways and processing of sensory signals are likely to be impaired; (2) an increased perception of esophageal stimulation reflects an exaggerated brainstem response and altered cortical processing of visceral sensation in patients with NCCP.

Evidence for involvement of nitric oxide (NO) or a related nitroso-compound in NANC inhibitory neurotransmission in the pigeon oesophageal smooth muscle.

In the pigeon oesophageal smooth muscle electrical field stimulation (EFS), in the presence of atropine and guanethidine, evoked TTX-sensitive inhibitory effects on both the electrical and mechanical activity. N(omega)-Nitro L-arginine (L-NA) (0.1-100 microM), an inhibitor of nitric oxide synthase, reduced the inhibitory EFS-evoked effects. Sodium nitroprusside (SNP) (10 microM), a NO-donor, mimicked the effects evoked by EFS. Apamin (1 microM) perfusion did not modify the inhibitory effects induced by SNP. Cystamine (10 microM), a guanylate-cyclase inhibitor, reduced the inhibitory effects elicited by EFS. This study shows a possible role for NO in the non-adrenergic non-cholinergic (NANC) inhibitory responses induced by EFS in the pigeon oesophagus.