Noninvasive electrical neuromodulation for gastrointestinal motility disorders.

INTRODUCTION: Gastrointestinal motility disorders are highly prevalent without satisfactory treatment. noninvasive electrical neuromodulation is an emerging therapy for treating various gastrointestinal motility disorders. AREAS COVERED: In this review, several emerging noninvasive neuromodulation methods are introduced, including transcutaneous auricular vagal nerve stimulation, percutaneous auricular vagal nerve stimulation, transcutaneous cervical vagal nerve stimulation, transcutaneous electrical acustimulation, transabdominal interference stimulation, tibial nerve stimulation, and translumbosacral neuromodulation therapy. Their clinical applications in the most common gastrointestinal motility are discussed, including gastroesophageal reflux disease, functional dyspepsia, gastroparesis, functional constipation, irritable bowel syndrome, and fecal incontinence. PubMed database was searched from 1995 to June 2023 for relevant articles in English. EXPERT OPINION: Noninvasive neuromodulation is effective and safe in improving both gastrointestinal symptoms and dysmotility; it can be used when pharmacotherapy is ineffective. Future directions include refining the methodology, improving device development and understanding mechanisms of action.

Therapeutic potential and mechanisms of sacral nerve stimulation for gastrointestinal diseases.

Background: The aim of this systemtic review is to introduce clinical applications (especially emerging) and potential mechanisms of sacral nerve stimulation (SNS) for treating various gastrointestinal diseases. Materials and Methods: PubMed and Web of Science were searched for studies published on SNS and its clinical applications in fecal incontinence (limited to systematic review and meta-analysis of clinical studies), constipation (limited to reviews and randomized control clinical studies), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and upper gastrointestinal motility disorders. The relevant studies were pooled, and their findings were summarized and discussed. Results: SNS is an approved method for treating fecal incontinence. Systematic review and meta-analysis demonstrated high efficacy of the SNS therapy for fecal incontinence. Increased anal sphincter pressure and improvement in rectal sensation were reported as major mechanisms involved in the SNS therapy. SNS has also been proposed for treating constipation, but the therapy has been shown ineffective. There is a lack in SNS methodological optimization and mechanistic research. A few basic and clinical studies have reported the potential of SNS for treating visceral pain in IBS. SNS seemed capable of improving mucosal barrier functions. Several case reports are available in the literature on the treatment of IBD with SNS. Several laboratory studies suggested therapeutic potential of a special method of SNS for IBD. Cholinergic anti-inflammatory mechanisms were reported. Due to a recently reported spinal afferent and vagal efferent pathway of SNS, a few preclinical studies reported the potential of SNS for upper gastrointestinal motility disorders. However, no clinical studies have been performed. Conclusions: SNS for fecal incontinence is a well-established clinical therapy. However, the current method of SNS is ineffective for treating constipation. Further methodological development and randomized clinical trials are needed to explore potential applications of SNS for IBS and IBD.

Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation.

BackgroundAbdominal pain and constipation are 2 main symptoms in patients with constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to investigate the effects and possible mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) in patients with IBS-C.MethodsForty-two patients with IBS-C were randomized into a 4-week sham-taVNS or taVNS treatment. The primary outcomes were complete spontaneous bowel movements per week (CSBMs/week) and visual analog scale (VAS) for abdominal pain. High-resolution anorectal manometry (HRAM) was performed to evaluate anorectal motor and sensory function. Cytokines and brain gut peptides were analyzed in blood samples. ECG was recorded for the assessment of autonomic function.ResultsCompared with sham-taVNS, (a) taVNS increased CSBMs/week (P = 0.001) and decreased VAS pain score (P = 0.001); (b) improved quality of life (P = 0.020) and decreased IBS symptom score (P = 0.001); (c) improved rectoanal inhibitory reflex (P = 0.014) and improved rectal sensation (P < 0.04); (d) decreased a number of proinflammatory cytokines and serotonin in circulation; and (e) enhanced vagal activity (P = 0.040). The vagal activity was weakly correlated with the CSBMs/week (r = 0.391; P = 0.010) and the VAS pain score (r = -0.347; P = 0.025).ConclusionsNoninvasive taVNS improves both constipation and abdominal pain in patients with IBS-C. The improvement in IBS-C symptoms might be attributed to the integrative effects of taVNS on intestinal functions mediated via the autoimmune mechanisms.Trial registrationwww.chictr.org.cn, no. ChiCTR2000029644.FundingNational Natural Science Foundation of China (grant no. 81970538 for FL).

Effects and mechanisms of acupuncture and electroacupuncture for functional dyspepsia: A systematic review.

BACKGROUND: Functional dyspepsia (FD) is a common digestive disease with limited therapeutic options. According to evidence-based clinical practice, acupuncture or electroacupuncture (EA) seems to be a promising therapy for patients with FD. However, there is still a lack of systematic reviews that have analyzed current clinical trials for a better understanding of mechanisms involved in the ameliorating effect of acupuncture and EA on FD. AIM: To evaluate the results and qualities of existing clinical evidence for researching the underlying mechanisms of acupuncture/EA in treating FD. METHODS: A systematic search of the literature was performed to identify randomized controlled trials in which research on the mechanism of acupuncture or EA was conducted in FD patients. Databases searched included PubMed, EMBASE, Cochrane Library, and Web of Science. Data extraction and quality assessment were completed by two investigators independently and the results of quality evaluation were exported through Review Manager V5.3. RESULTS: Eight studies were included in this review with a total of 17 items for detecting techniques for mechanistic research. Positive effects of acupuncture and EA were observed in regulating gastric motility, gastric accommodation, mental status, gastrointestinal hormones, and central and autonomic functions while improving dyspeptic symptoms and quality of life. CONCLUSION: The key findings of this systematic review support the potential of acupuncture and EA in altering the heterogeneous pathophysiology in patients with FD. However, high-quality studies with well-planned designs are necessary to provide more credible evidence.

Ameliorating Effects and Mechanisms of Intra-Operative Vagal Nerve Stimulation on Postoperative Recovery After Sleeve Gastrectomy in Rats.

PURPOSE: Sleeve gastrectomy is a common bariatric procedure. The aim of this study was to explore the effects and mechanisms of intra-operative vagal nerve stimulation (iVNS) on postoperative recovery after sleeve gastrectomy in rats. MATERIALS AND METHODS: Rats were randomly divided into groups of sham-iVNS (n = 12) and iVNS (n = 12), and received sleeve gastrectomy, and were implanted electrodes for the electrocardiogram (ECG) and gastric pace-making activity or slow wave (GSW). iVNS or sham-iVNS was performed during surgery. Postoperative animal behaviors, pain, gastrointestinal functions, autonomic functions, inflammatory cytokines, and hormones in plasma were assessed. RESULTS: In comparison with sham-iVNS, (1) iVNS accelerated the first drinking time (P = 0.01) and first defecation time (P = 0.02), increased the weight of stool in postoperative day (POD) 1 (P = 0.01) and POD3 (P = 0.01), and reduced postoperative pain at 24 h after surgery (P = 0.01); (2) physiologically, iVNS improved gastric emptying (P < 0.01) at 72 h after surgery, and increased the dominant frequency (P < 0.01) and the percentage of normal GSW (P = 0.04) at 6 h after surgery; (3) mechanistically, iVNS increased vagal activity and decreased sympathovagal ratio at 6 h (vagal, P < 0.01; sympathovagal ratio, P < 0.01) and 24 h (vagal, P = 0.02; sympathovagal ratio, P = 0.01) after surgery, increased the plasma pancreatic polypeptide (P = 0.03) at 1 h after surgery, and decreased the plasma tumor necrosis factor-α (TNF-α) at 1 h (P = 0.02) and 6 h (P = 0.03) and the plasma interleukin-6 (IL-6) at 1 h (P = 0.02) after surgery. CONCLUSION: Intra-operative VNS is effective in accelerating post-surgical recovery in rats after sleeve gastrectomy by enhancing gastric pace-making activity and suppressing proinflammatory cytokines mediated via the autonomic mechanisms.

Electroacupuncture Ameliorates Gastric Hypersensitivity via Adrenergic Pathway in a Rat Model of Functional Dyspepsia.

OBJECTIVE: Electroacupuncture (EA) is effective in treating visceral pain associated with functional dyspepsia (FD). The aim of this study was to explore the effect of chronic EA (CEA) on gastric hypersensitivity and the involvement of sympathetic nervous system in a rodent model of FD. MATERIALS AND METHODS: Gastric hypersensitivity in adulthood was induced by iodoacetamide (IA) in neonatal rats. The IA-treated rats were randomized to receive no treatment (control), sham-CEA, CEA, or adrenergic antagonists, for one week. Gastric sensitivity to graded gastric distensions was then assessed by electromyogram (EMG) analysis. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) to derive the low-frequency (LF, sympathetic activity) and high-frequency (HF, mainly vagal activity) components expressed as percentage of total spectral power. Blood was collected for the measurement of corticosterone (CORT) and norepinephrine (NE). RESULTS: 1) CEA, but not sham-CEA, reduced the EMG response to graded gastric distension in IA-treated control rats at 40 mmHg (128 ± 6% vs. 171 ± 15%, p = 0.009), 60 mmHg (204 ± 14% vs. 271 ± 24%, p = 0.010) and 80 mmHg (269 ± 19% vs. 364 ± 33%, p = 0.025), respectively. 2) CEA, but not sham CEA, increased HF component (0.61 ± 0.02 vs. 0.46 ± 0.04 in IA-treated rats, p = 0.003) and decreased LF component (0.39 ± 0.02 vs. 0.54 ± 0.04, p = 0.003). 3) Adrenergic antagonists reduced the EMG response to graded gastric distension. 4) CEA significantly reduced plasma CORT and NE in IA-treated rats. CONCLUSIONS: EA ameliorates gastric hypersensitivity in IA-treated rats and the effect may be related to the improved sympathovagal balance and the decrease of stress hormones.

Anti-inflammatory effects of sacral nerve stimulation: a novel spinal afferent and vagal efferent pathway.

Sacral nerve stimulation (SNS) was reported to improve 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The aim of this study was to investigate whether the SNS anti-inflammatory effect is mediated via the local sacral splanchnic nerve or the spinal afferent-vagal efferent-colon pathway. Under general anesthesia, rats were administrated with TNBS intrarectally, and bipolar SNS electrodes were implanted unilaterally at S3. The sacral and vagal nerves were severed at different locations for the assessment of the neural pathway. SNS for 10 days improved colonic inflammation only in groups with intact afferent sacral nerve and vagus efferent nerve. SNS markedly increased acetylcholine and anti-inflammatory cytokines (IL-10) and decreased myeloperoxidase and proinflammatory cytokines (IL-2, IL-17A, and TNF-α) in colon tissues. SNS increased the number of c-fos-positive cells in the brain stem and normalized vagal activity measured by spectral analysis of heart rate variability. SNS exerts an anti-inflammatory effect on TNBS-induced colitis by enhancing vagal activity mediated mainly via the spinal afferent-brain stem-vagal efferent-colon pathway.NEW & NOTEWORTHY Our findings support that there is a possible sacral afferent-vagal efferent pathway that can transmit sacral nerve stimulation to the colon tissue. Sacral nerve stimulation can be carried out by spinal cord afferent to the brain stem and then by the vagal nerve (efferent) to the target organ.

Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway.

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Electrical Acustimulation in Patients With Gastroesophageal Reflux Disease.

BACKGROUND/AIM: Gastric dysmotility is one of pathophysiologies of gastroesophageal reflux disease (GERD). The aim of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on gastric accommodation and gastric slow waves, and evaluate possible mechanisms in patients with GERD. METHODS: Thirty patients were studied in two randomized sessions of sham-TEA and TEA with the measurements of esophageal high-resolution manometry (HRM), gastric accommodation assessed by a nutrient-drinking test, electrogastrogram (EGG), electrocardiogram (ECG), and postprandial dyspeptic symptoms. RESULTS: Compared with sham-TEA, TEA improved nutrient drinking-induced fullness (42.0 ± 3.3 vs. 31.0 ± 3.5, P = 0.003) at 10 min after the drink, and belching right after the drink (22.0 ± 4.6 vs. 11.7 ± 3.1, P = 0.012) and at 10 min (16.0 ± 3.8 vs. 3.0 ± 1.5, P = 0.002) after the drink. TEA also improved gastric accommodation (954 ± 37 mL vs. 857 ± 47 mL, P = 0.001) and normalized maximal drink-induced impairment in gastric slow waves. Concurrently, TEA enhanced vagal activity assessed from spectral analysis of heart rate variability in the postprandial state (0.42 ± 0.03 vs. 0.49 ± 0.04, P = 0.039). The vagal activity was positively correlated with the percentage of normal slow waves (r = 0.528; P = 0.003) and negatively correlated with the regurgitation score (r = -0.408, P = 0.025). CONCLUSIONS: Acute TEA increases gastric accommodation, improves gastric slow waves, and reduces postprandial fullness and belching, possibly mediated via the vagal mechanisms.

Systematic review on gastric electrical stimulation in obesity treatment.

Introduction: Obesity is a very common public health problem worldwide. However, there is a lack of effective therapies. Only a small portion of patients with morbid obesity are accepting bariatric surgery as the last option due to the risks associated with invasive therapy. Areas covered: In this paper, we review an emerging weight loss treatment: gastric electrical stimulation (GES). The feasibility of GES as a potential therapy for obesity is introduced. Methodologies and parameters of GES are presented. Several GES methods for treating obesity and their effects on food intake and body weight are presented. Possible mechanisms involved in the anti-obesity effect of GES are discussed. Finally, our comments on the potential of GES for obesity and expectations for future development of the GES therapy are provided. The PubMed central database was searched from inception to May 2019. The literature search used the following terms: 'Gastric electrical stimulation' combined with 'obesity' and 'Implantable gastric stimulation' and 'pharmaceutical therapy' and 'bariatric surgery'. Expert opinion: There is a potential to use GES for treating obesity. However, more efforts are needed to develop appropriate stimulation devices and to design an adequate therapy for treating obesity in humans.

Vagal Nerve Stimulation for Glycemic Control in a Rodent Model of Type 2 Diabetes.

BACKGROUND: Vagal nerve stimulation (VNS) has been reported to reduce body weight and improve sympathovagal imbalance in both basic and clinical studies. Its effects on glycemic control were however unclear. The aims of this study were to investigate the effects of VNS with various parameters on blood glucose and its possible mechanisms in rats. METHODS: A hyperglycemic rodent model induced by glucagon was used initially to optimize the VNS parameters; then, a type 2 diabetic rodent model induced by high-fat diet combined with streptozotocin was used to validate the VNS method. The VNS electrodes were implanted at the dorsal subdiaphragmatic vagus; three subcutaneous electrodes were implanted at the chest area for recording electrocardiogram in rats induced by glucagon. RESULTS: (1) VNS with short pulse width of 0.3 ms but not 3 ms reduced blood glucose during an oral glucose tolerance test (OGTT), with a 38.4% reduction at 15 min and 26.9% at 30 min (P < 0.05, vs. sham-VNS respectively). (2) VNS at low frequency of 5 Hz but not 14 Hz or 40 Hz reduced blood glucose during the OGTT (P < 0.05, vs. sham-VNS). (3) Intermittent VNS was more potent than continuous VNS (P < 0.01). (4) No difference was found between unilateral VNS and bilateral VNS. (5) VNS enhanced vagal activity (P = 0.005). (6) The hypoglycemic effect of VNS was blocked by glucagon-like peptide-1 (GLP-1) antagonist exendin-4. CONCLUSIONS: VNS at 5 Hz reduces blood glucose in diabetic rats by enhancing vagal efferent activity and the release of GLP-1.

Roles of ATP sensitive potassium channel in modulating gastric tone and accommodation in dogs.

OBJECTIVE: The ATP sensitive potassium (KATP) channel plays an important role in the regulation of resting membrane potential and membrane excitability. The role of the KATP channel in modulating gastric motility is unclear. The aim of this study was to investigate the role and mechanism of the KATP channel in modulating gastric tone and accommodation in dogs. MATERIALS AND METHODS: Gastric volume under a constant pressure reflecting gastric tone was measured using a barostat device in dogs equipped with a gastric cannula. Gastric accommodation was evaluated by the difference in gastric volume before and after a liquid meal. The roles of cholinergic and nitrergic pathways in the inhibitory effect of pinacidil (a KATP opener) were assessed. RESULTS: 1) Pinacidil dose-dependently decreased gastric tone at a dosage of 30 (p = 0.628), 100 (p = 0.013) and 300 µg kg-1 (p < 0.001). 2) Glibenclamide, a KATP blocker, completely blocked the inhibitory effect of pinacidil on gastric tone. 3) Atropine did not block the inhibitory effect of pinacidil on gastric tone but Nω-Nitro-L-arginine methyl ester markedly attenuated the inhibitory effect of pinacidil (p = 0.004). 4) Glibenclamide significantly reduced gastric accommodation (p < 0.001) while pinacidil had no effects on gastric accommodation. 5) Glibenclamide significantly reduced nitric oxide donor sodium nitroprusside-induced gastric relaxation. CONCLUSIONS: These findings indicate that the KATP channel plays an important role in modulating gastric tone and accommodation in dogs. The inhibitory effect of pinacidil on gastric tone was through the nitrergic pathway as well as acting directly on smooth muscle cells.

An alternative to current therapies of functional dyspepsia: self-administrated transcutaneous electroacupuncture improves dyspeptic symptoms.

Functional dyspepsia is of high prevalence with little treatment options. The aim of this study was to develop a new treatment method using self-management transcutaneous electroacupuncture (TEA) for functional dyspepsia (FD). Twenty-eight patients with FD were enrolled and underwent a crossover clinical trial with 2-week TEA at ST36 and PC6 and 2-week sham-TEA at nonacupuncture sham-points. Questionnaires were used to assess symptoms of dyspepsia and quality of life. Physiological testing included gastric emptying and electrogastrography. It was found that (1) TEA but not sham-TEA significantly improved dyspeptic symptoms and 4 domains in quality of life; improvement was also noted in self-rated anxiety and depression scores; (2) gastric emptying was significantly and substantially increased with 2-week TEA but not sham-TEA; and (3) gastric accommodation was also improved with TEA but not sham-TEA, reflected as increased ingested nutrient volumes at the levels of satiety and maximum tolerance. These findings suggest a therapeutic potential of self-administrated TEA method for functional dyspepsia, possibly attributed to improvement in gastric motility.

Rimonabant, gastrointestinal motility and obesity.

BACKGROUND: Obesity and overweight affect more than half of the US population and are associated with a number of diseases. Rimonabant, a cannabinoid receptor 1 blocker in the endocannabinoid (EC) system, was indicated in Europe for the treatment of obesity and overweight patients with associated risk factors but withdrawn on Jan, 2009 because of side effects. Many studies have reported the effects of rimonabant on gastrointestinal (GI) motility and food intake. THE AIMS OF THIS REVIEW ARE: to review the relationship of EC system with GI motility and food intake;to review the studies of rimonabant on GI motility, food intake and obesity;and to report the tolerance and side effects of rimonabant. METHODS: THE LITERATURE (PUBMED DATABASE) WAS SEARCHED USING KEYWORDS: rimonabant, obesity and GI motility. RESULTS: GI motility is related with appetite, food intake and nutrients absorption. The EC system inhibits GI motility, reduces emesis and increases food intake; Rimonabant accelerates gastric emptying and intestinal transition but decreases energy metabolism and food intake. There is rapid onset of tolerance to the prokinetic effect of rimonabant. The main side effects of rimonabant are depression and GI symptoms. CONCLUSIONS: Rimonabant has significant effects on energy metabolism and food intake, probably mediated via its effects on GI motility.

Exogenous nitrergic pathway involved in the regulation of gastric myoelectrical activity in dogs.

OBJECTIVE: Although the effect of nitric oxide (NO) on gastric motility has been investigated in numerous studies, its effects on gastric slow waves and spike activity which regulate gastric motility remained largely unknown. The aim of this study was to test the hypothesis that NO would impair gastric slow waves by reducing their regularity and amplitude as well as contraction-related spike activity. MATERIAL AND METHODS: The study required four sessions in 8 dogs, 2 weeks after the implantation of four pairs of electrodes along the greater curvature of the stomach. In each session, saline, L-arginine (L-Arg) (75 mg/kg), NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg) or L-Arg + L-NAME was given intravenously (IV) after a 30-min baseline recording in the fasting state. A solid test meal (200 g) was ingested 30 min after the IV injection of one of the medications. Gastric myoelectrical activity was recorded for 30 min at baseline, 30 min after the IV injection and 60 min after the meal. RESULTS: The frequency, amplitude and rhythmicity of gastric slow waves were not affected by NO. L-NAME significantly increased spike activity in the fasting state but not in the fed state. L-Arg did not reduce the number of spike bursts per minute (NSPM) in the fed state. Postprandially, there was a significant decrease in slow wave frequency but a substantial increase in the strength and frequency of spike activity. CONCLUSIONS: Exogenous NO has no effect on the frequency, amplitude or regularity of gastric slow waves; inhibition of NO increases spike activity in the fasting state but not in the fed state.

Excitatory effects of synchronized intestinal electrical stimulation on small intestinal motility in dogs.

The aim of this study was to investigate effects of synchronized intestinal electrical stimulation (SIES) on small intestinal motility in dogs. Seventeen dogs were equipped with a duodenal cannula for the measurement of small bowel motility using manometry; an additional cannula was equipped in six of the dogs with 1.5 m distal to the first one for the measurement of small intestinal transit. Two pairs of bipolar electrodes were implanted on the small intestinal serosa with an interval of 5 cm; glucagon was used to induce postprandial intestinal hypomotility. Eleven dogs were used for the assessment of the small intestinal contractions in both fasting and fed states. The other six dogs were used for the measurement of small intestinal transit. We found that 1) SIES induced small intestinal contractions during phase I of the migrating motor complex (MMC) (contractile index or CI: 5.2 +/- 0.6 vs. 10.3 +/- 0.7, P = 0.003); 2) in the fed state, SIES significantly improved glucagon-induced small intestinal postprandial hypomotility (CI: 3.4 +/- 0.5 vs. 6.0 +/- 0.3, P = 0.03); 3) SIES significantly accelerated small intestinal transit delayed by glucagon (70.4 +/- 3.1 vs. 44.5 +/- 3.1 min, P < 0.01); 4) there was a negative correlation between the CI and transit time (r = -0.427, P = 0.048); and 5) the excitatory effect of SIES was blocked by atropine. SIES may have a therapeutic potential for treating patients with small intestinal disorders.

Roles of putative neurotransmitters in the regulation of gastric and intestinal slow waves in conscious dogs.

BACKGROUND AND AIMS: Slow waves play an important role in controlling the frequency and propagation of gastrointestinal contractions. However, mechanisms involved in the modulation of slow wave activity in vivo are still unclear. In this study, the roles of different neurotransmitters in the regulation of gastrointestinal slow waves were investigated in conscious dogs. METHODS: Female dogs implanted with electrodes in the stomach and the small bowel were used in a seven-session study. Gastrointestinal myoelectrical activity was recorded at baseline and after i.v. saline, atropine, atropine methyl nitrate, guanethidine, Nomega-nitro-L-arginine (L-NNA), ondansetron or naloxone. RESULTS: Both atropine and atropine methyl nitrate induced tachygastria, bradygastria and arrhythmia. No difference was noted in the effects between atropine and atropine methyl nitrate. L-NNA increased the dominant frequency of small-intestinal slow waves but had no effect on gastric slow waves. Guanethidine, ondansetron and naloxone did not affect the dominant frequency, power or percentage of normal gastrointestinal slow waves. CONCLUSION: Acetylcholine acting at muscarinic receptors seems to play an important role in the regulation of gastric slow waves. Nitric oxide may play a role in modulating intestinal slow waves but not gastric slow waves. Sympathetic pathways, 5-HT(3) receptors and opioid receptors (especially micro-opioid receptors) do not play a role in the regulation of gastric or intestinal slow waves under normal physiological conditions.