Electroacupuncture via chronically implanted electrodes improves gastric dysmotility mediated by autonomic-cholinergic mechanisms in a rodent model of functional dyspepsia.

BACKGROUND: Electroacupuncture (EA) has been shown to be effective in reducing symptoms in patients with functional dyspepsia (FD). However, its mechanisms remain largely unknown. The aim of this study was to investigate mechanisms of the prokinetic effects of EA in a rodent model of FD. METHODS: A FD model was established by neonatal treatment of iodoacetamide (IA). Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of gastric slow waves (GSW) and electrodes into acupoints ST36 for EA. Autonomic functions were assessed by the spectral analysis of heart rate variability. KEY RESULTS: (i) The IA-treated rats ("FD" rats) showed increased dysrhythmia in both fasting and fed states (P < .01) as well as during rectal distention (P < .02). EA reduced the percentage of dysrhythmia (P < .05 for both fasting and fed) and normalized RD-induced impairment in GSW in "FD" rats. Atropine blocked the effect of EA on GSW. (ii) "FD" rats showed delayed gastric emptying (P = .001 vs control) that was accelerated with EA (P = .01, vs sham-EA). (iii) "FD" rats showed increased plasma norepinephrine (P = .006, vs control) that was suppressed with EA (P = .003) and reduced vagal activity that was improved with EA. CONCLUSIONS AND INFERENCES: Gastric motility (GSW and GE) is impaired in rats treated with IA, possibly attributed to impaired autonomic functions. EA improves GSW and accelerates GE mediated via the autonomic and cholinergic mechanisms.

Electroacupuncture treatments for gut motility disorders.

Functional gastrointestinal (GI) diseases are common and there are patients who are refractory to medical therapies as not all treatments work in all patients. Consequently, a large number of patients with functional GI diseases use complementary and alternative medicine, such as acupuncture or electroacupuncture (EA). In this issue, Zheng et al. reported interesting results of a multi-center placebo-controlled clinical study on the use of EA for treating refractory functional dyspepsia; another study reported a multi-center clinical trial on EA for chronic functional constipation; Liang et al. studied mechanisms of EA involving enteric nervous system and neurotransmitters in treating constipation in rats. While controversial reports are available in the literature, EA with appropriate methodologies as shown in these recent studies is believed to be effective in treating certain functional GI diseases. In this mini-review, a number of clinical studies, including those included in this issue on the use of EA for treating gastro-esophageal reflux, functional dyspepsia, irritable bowel syndrome, and constipation are reviewed. Some critically important issues, such as the choice of stimulation parameters for EA, the administration frequency of the therapy, and the appropriate choice of placebo for clinical research are also discussed. Mechanisms of action involved in the therapeutic effects of EA for gut dysmotility and future research directions are also presented.

Efficacy of needleless transcutaneous electroacupuncture in synchronization with breathing for symptomatic idiopathic gastroparesis: A blinded and controlled acute treatment trial.

BACKGROUND: Needleless transcutaneous electroacupuncture (TEA) improves nausea and myoelectrical activity in diabetic gastroparesis (GP). Synchronized TEA (STEA), which combines synchronized breathing with TEA, is more potent than TEA in enhancing vagal activity in healthy subjects. AIMS: To investigate whether STEA improves symptoms, electrogastrogram (EGG) and vagal activity in idiopathic gastroparesis (IGP). METHODS: Eighteen IGP subjects underwent 2 randomized visits (sham at non-acupoints or real STEA at acupoints) consisted of a 30-minute baseline, an Ensure challenge to provoke nausea, followed by 60-minute treatment with sham or real STEA, and 15-minute observation period. Severity of nausea, EGG, and vagal activity (based on electrocardiogram and serum Pancreatic Polypeptide, PP) were recorded. RESULTS: In sham or STEA, the nausea scores of 2.7 ± 0.5 and 1.9 ± 0.5 at fasting baseline, respectively, increased to 5.9 ± 0.4 and 5.8 ± 0.3 during Ensure test (P < .05, vs baseline), subsequently reduced to 3.4 ± 0.6 with sham or 3.6 ± 0.6 with STEA, respectively (P < .05, vs Ensure period). Experiments with sham and STEA started with similar % of normal waves on EGG (66.4 ± 3.9 and 61.8 ± 3.0, respectively); decreased to 63. 5 ± 4.1 and 58.2 ± 2.8 during the Ensure test. After STEA, there was ~24% increase in % of normal waves, significantly different from the sham (6.0%) (P < .01). In sham or STEA, vagal activity was identical at baseline and after the Ensure. STEA induced a 3-fold increase in vagal activity compared with sham (P < .01). Ensure increased serum PP levels, and both treatments decreased the PP CONCLUSIONS: In IGP, STEA is not superior to Sham in decreasing nausea, but is more effective in improving gastric dysrhythmia.

Developments in Gastrointestinal Electrical Stimulation.

Electrical stimulation of the gastrointestinal (GI) tract, analogous to pacing the human heart, is an attractive idea. This is because these organs, like the heart, have their own natural pacemakers, and the electrical signals they generate can be altered by externally delivering certain types of electric currents via intraluminal or serosal electrodes to certain areas of the GI tract. A number of studies on animals have been accomplished successfully to treat a variety of disease models, including gastroparesis, dumping, and short bowel syndrome. Over the past 10 years or so, electrical stimulation of the GI tract has received increasing attention among researchers and clinicians because of new techniques, such as implantable devices, and promising results achieved in treatment of gastroparesis and morbid obesity. The objective of this article is to review the advances in electrical stimulation of the gastrointestinal tract. First the electrophysiology of the GI tract and history of GI electrical stimulation are introduced. Then various methods of electrical stimulation of the stomach and small bowel in healthy animals and models of GI diseases are reviewed. Finally clinical applications of electrical stimulation to GI disorders and their possible mechanisms are discussed.

Anorectal manometry: Should it be performed in a seated position?

BACKGROUND: Anorectal manometry (ARM) is typically preformed in a lateral position. This non-physiological testing position has produced an unexpected negative rectoanal pressure gradient (RAPG, i.e. difference between rectal and anal pressure) with normal defecation. This study was designed (i) to study differences in ARM parameters between water-perfused and solid-state sensors and between lateral and seated positions and (ii) to investigate the roles of ARM parameters in predicting balloon expulsion. METHODS: ARM was performed in 18 healthy volunteers (HV) and 60 patients with functional constipation (FC) under three randomized conditions: water-perfused in lateral position, solid-state in lateral position, and solid-state in seated position, followed by a balloon expulsion test in seated position. KEY RESULTS: i) Under the same lateral position, solid-state sensors produced higher rectal resting pressure and RAPG than water-perfused sensors. ii) Using the solid-state sensors, ARM in the seated position revealed higher resting rectal pressure (34.9 vs 10.9 mmHg in HV, 30.9 vs 10.6 mmHg in FC, both P<.001) and higher RAPG (22.6 vs -6.2 mmHg in HV, 17.1 vs -8.1 mmHg in FC, both P<.001) than the lateral position. iii) When ARM was performed using solid-state sensors in seated position, RAPG was predictive of balloon expulsion; using 10 mmHg as a threshold, RAPG could predict balloon expulsion with specificity of 82% and sensitivity 77%. CONCLUSIONS AND INFERENCE: ARM performed in a seated position using solid-state sensors seems more accurate in assessing rectal pressure, and the RAPG measured under these conditions is predictive of balloon expulsion in FC patients.

Auricular vagal nerve stimulation ameliorates burn-induced gastric dysmotility via sympathetic-COX-2 pathways in rats.

BACKGROUND: Severe burn injury has been demonstrated to delay gastric emptying. The aim of this study was to investigate effects and cellular mechanisms of auricular electroacupuncture (AEA) at the acupoints innervated by the auricular branch of vagus nerve on burn-induced gastric dysmotility in rats. METHODS: Propranolol (ß-adrenoceptor antagonist) was injected intraperitoneally after the rats underwent burn injury. All experiments were performed 6 h following burn/sham burn injury. AEA was performed at bilateral auricular acupoints for 45 min. Electrocardiogram was recorded for 30 min. Plasma hormones were measured; cyclooxygenase (COX)-2 expressions in gastric tissue were measured using western blotting and real-time RT-PCR. KEY RESULTS: (i) Burn injury delayed gastric emptying (p = 0.006) and AEA increased gastric emptying by 49% (p = 0.045). (ii) Burn injury evoked a significant elevation in plasma noradrenaline, which was suppressed by AEA. (iii) Burn injury significantly increased protein and mRNA expressions of COX-2 in gastric fundus and antrum. AEA suppressed burn-induced increase in protein expressions, but not mRNA expressions of COX-2. CONCLUSIONS & INFERENCES: Burn injury delays gastric emptying by up-regulating COX-2 attributed to sympathetic overactivity. AEA improves burn-induced delay in gastric emptying, possibly mediated via the sympathetic-COX-2 pathway.

Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats.

BACKGROUND: Hyperglycemia is known to induce dysrhythmias in the stomach; however, it is unknown whether they are also induced in the small intestine. Autonomic dysfunction is commonly noted in diabetes but the role it plays in hyperglycemia-induced dysrhythmias remains unknown. This study aimed to explore the effects of hyperglycemia on intestinal myoelectrical activity and the role of autonomic functions in hyperglycemia. METHODS: Small intestinal myoelectrical activity (slow wave and spike activity) and autonomic functions (assessed by the spectral analysis of heart rate variability) were measured in Goto-Kakizaki diabetic rats and control rats treated with acute glucagon. Blood glucose was measured and its correlation with intestinal slow waves was determined. KEY RESULTS: (1) The diabetic rats showed reduced regularity in intestinal slow waves in fasting and fed states (p < 0.001 for both), and increased sympathovagal balance (p < 0.05) in comparison with the control rats. The regularity in intestinal slow waves was negatively correlated with the HbA1c level in all rats (r = -0.663, p = 0.000). (2) Glucagon injection in the control rats induced transient hyperglycemia, intestinal slow wave dysrhythmias and impaired autonomic functions, similar to those observed in the diabetic rats. The increase in blood glucose was correlated with the decrease in the regularity of intestinal slow waves (r = -0.739, p = 0.015). CONCLUSIONS & INFERENCES: Both spontaneous and glucagon-induced hyperglycemia results in slow wave dysrhythmias in the small intestine. Impairment in autonomic functions (increased sympathovagal balance) may play a role in hyperglycemia-induced dysrhythmias.

Down-regulation of A-type potassium channel in gastric-specific DRG neurons in a rat model of functional dyspepsia.

BACKGROUND: Although without evidence of organic structural abnormalities, pain or discomfort is a prominent symptom of functional dyspepsia and considered to reflect visceral hypersensitivity whose underlying mechanism is poorly understood. Here, we studied electrophysiological properties and expression of voltage-gated potassium channels in dorsal root ganglion (DRG) neurons in a rat model of functional dyspepsia induced by neonatal gastric irritation. METHODS: Male Sprague-Dawley rat pups at 10-day old received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days and studied at adulthood. Retrograde tracer-labeled gastric-specific T8 -T12 DRG neurons were harvested for the patch-clamp study in voltage and current-clamp modes and protein expression of K(+) channel in T8 -T12 DRGs was examined by western blotting. KEY RESULTS: (1) Gastric specific but not non-gastric DRG neurons showed an enhanced excitability in neonatal IA-treated rats compared to the control: depolarized resting membrane potentials, a lower current threshold for action potential (AP) activation, and an increase in the number of APs in response to current stimulation. (2) The current density of tetraethylammonium insensitive (transiently inactivating A-type current), but not the tetraethylammonium sensitive (slow-inactivating delayed rectifier K(+) currents), was significantly smaller in IA-treated rats (65.4 ± 6.9 pA/pF), compared to that of control (93.1 ± 8.3 pA/pF). (3) Protein expression of KV 4.3 was down-regulated in IA-treated rats. CONCLUSIONS & INFERENCES: A-type potassium channels are significantly down-regulated in the gastric-specific DRG neurons in adult rats with mild neonatal gastric irritation, which in part contribute to the enhanced DRG neuron excitabilities that leads to the development of gastric hypersensitivity.

Decreased L-type calcium current in antral smooth muscle cells of STZ-induced diabetic rats.

BACKGROUND: Diabetic gastroparesis (delayed gastric emptying) is associated with antral hypomotility. L-type Ca(2+) channels play an important role in generation of action potentials and activation of contractions. This study was designed to investigate if the function of the L-type Ca(2+) channels of antral circular smooth muscle cells (SMCs) is impaired in streptozotocin (STZ)-induced diabetic rats. METHODS: Eight weeks after the injection of STZ or vehicle, whole-cell patch clamp was used to record Ca(2+) currents, and isometric tension recording was used to measure Ca(2+) influx-induced contractions in circular muscle strips. Solid gastric emptying was measured in diabetic and control rats. Protein expression of Ca(2+) αlC-subunit in antral smooth muscles was compared between diabetic and control rats. KEY RESULTS: (1) Solid gastric emptying, independent of age or bodyweight, was slower in the diabetic rats, even after acute correction of hyperglycemia. (2) Verapamil, a potent calcium channel blocker, dose dependently reduced solid gastric emptying in normal rats. (3) Current density of L-type Ca(2+) channel at 10 mV in antral circular SMCs was significantly decreased in the diabetic rats (-9.8 ± 0.7 pA/pF vs -15.9 ± 1.0 pA/pF in control, p < 0.001). However, protein expression of the Ca(2+) channel in antral muscles did not differ between diabetic and control rats. (4) Contractile responses to 1 and 3 mM [Ca(2+) ] were significantly reduced in the diabetic antral circular muscle strips, indicative of reduced Ca(2+) influx. CONCLUSIONS & INFERENCES: These data suggested that the decreased L-type Ca(2+) current in antral SMCs may contribute to antral hypomotility in STZ-induced diabetic rats.

Effects and mechanisms of gastric electrical stimulation on visceral pain in a rodent model of gastric hyperalgesia secondary to chemically induced mucosal ulceration.

BACKGROUND: Gastric electrical stimulation (GES) has been suggested as a potential treatment for patients with gastric motility disorders. The aim of this study was to examine the effects and mechanisms of GES on visceral pain in awaken rats. METHODS: Under anesthesia, acetic acid was injected into the submucosal layer of the stomach wall in Sprague-Dawley (SD) male rats. Each rat was chronically placed with an intragastric balloon and two pairs of electrodes on gastric serosa for GES and at the neck muscles for electromyography (EMG) recordings respectively. The study was composed of four experiments. Exp 1 was designed to determine optimal GES parameters in reducing EMG response to gastric distention (GD). Exp 2 was performed to investigate the effect of GES on gastric tone/accommodation. Exp 3 was to investigate if the opioid pathway was involved in the analgesic effects of GES. Exp 4 was to assess the effectiveness of GES on the spinal cord neurons (T9-T10) responding to GD. KEY RESULTS: (i) Gastric electrical stimulation with a train on of 0.1 s and off of 0.4 s, 0.25 ms, 100 Hz, and 6 mA significantly reduced GD-induced EMG responses at GD 40, 60, and 80 mmHg. (ii) The inhibitory effects of GES on the GD-induced EMG responses were blocked by Naloxone. (iii) GES inhibited 90% of high-threshold (HT) spinal neurons in response to GD. However, GES with the same parameters only suppressed 36.3% low-threshold (LT) neuronal response to GD. CONCLUSIONS & INFERENCES: Gastric electrical stimulation with optimal parameters inhibits visceral pain; the analgesic effect of GES on visceral pain is mediated via the endogenous opioid system and the suppression of spinal afferent neuronal activities.

Therapeutic potential of spinal cord stimulation for gastrointestinal motility disorders: a preliminary rodent study.

BACKGROUND: Spinal cord electrical stimulation (SCS) has been applied for the management of chronic pain. Most of studies have revealed a decrease in sympathetic activity with SCS. The aim of this study was to investigate the effects and mechanisms of SCS on gastrointestinal (GI) motility in healthy and diabetic rats. METHODS: Male rats chronically implanted with a unipolar electrode at T9/T10 were studied. The study included four experiments to assess the effects of SCS on (1) gastric tone; (2) gastric emptying of liquids and intestinal transit; (3) gastric emptying of solids; and (4) sympathovagal balance in healthy rats and/or in Streptozotocin (STZ)-induced diabetic rat. KEY RESULTS: (1) Spinal cord stimulation intensity dependently increased gastric tone in healthy rats. The gastric volume was 0.97 ± 0.15 mL at baseline, and decreased to 0.92 ± 0.16 mL with SCS of the 30% motor threshold (MT; p = 0.13 vs baseline), 0.86 ± 0.14 mL with 60% MT (p = 0.045 vs baseline), and 0.46 ± 0.19 mL with 90% MT (p = 0.0050 vs baseline). (2) Spinal cord stimulation increased gastric emptying of liquids by about 17% and accelerated small intestinal transit by about 20% in healthy rats (p < 0.001). (3) Spinal cord stimulation accelerated gastric emptying of solids by about 24% in healthy rats and by about 78% in diabetic rats. (4) Spinal cord stimulation decreased sympathetic activity (1.13 ± 0.18 vs 0.68 ± 0.09, p < 0.04) and sympathovagal balance (0.51 ± 0.036 vs 0.40 ± 0.029, p = 0.028). CONCLUSIONS & INFERENCES: Spinal cord stimulation accelerates gastric emptying of liquids and solids, and intestinal transit, probably by inhibiting the sympathetic activity. Spinal cord stimulation may have a therapeutic potential for treating GI motility disorders.

Acute and chronic effects of desvenlafaxine on gastrointestinal transit and motility in dogs.

BACKGROUND: Antidepressants are commonly used for treating functional gastrointestinal (GI) diseases. However, little is known whether antidepressants improve or impair GI motility. This study aimed at exploring possible effects of a serotonin-norepinephrine reuptake inhibitor, desvenlafaxine succinate (DVS), on GI motility in dogs. METHODS: Eight dogs chronically implanted with a duodenal cannula and a colon cannula were used in the study. Experiments were performed to assess the effects of a single dose of DVS (50 or 100 mg) and DVS given 50 mg once a day for 2 weeks on gastric emptying of solid, small intestinal transit, and colon transit and contractions. KEY RESULTS: (1) DVS significantly delayed gastric emptying of solid at a single dose of 50 or 100 mg. The inhibitory effect on gastric emptying was completely blocked by guanethidine (an adrenergic blocking agent). (2) DVS at a single dose of 50 or 100 mg accelerated colon transit, but showed no effects on small bowel transit. (3) DVS at a single dose of 50 mg enhanced colon contractions and guanethidine blocked the effect. (4) Surprisingly, DVS given at 50 mg once daily for 2 weeks did not alter gastric emptying, small bowel transit or colon transit. CONCLUSIONS & INFERENCES: Acute DVS delays gastric emptying of solid and enhances the contractions of the colon, which may be mediated via the sympathetic mechanism. Acute DVS promotes the transit of the colon but not the small intestine. However, chronic administration of DVS does not seem to alter GI motility.

Electroacupuncture improves burn-induced impairment in gastric motility mediated via the vagal mechanism in rats.

BACKGROUND: Delayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns. METHODS: Male rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24 h post severe burns. KEY RESULTS: (i) Burn delayed GE (P < 0.001). Electroacupuncture improved GE 6 and 24 h post burn (P < 0.001). Vagotomy blocked the EA effect on GE. (ii) Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24 h post burn (P = 0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P = 0.004) and 24 h post burn (P = 0.03, vs sham-EA). (iv) Electroacupuncture attenuated burn-induced increase in plasma IL-6 at both 6 (P = 0.03) and 24 h post burn (P = 0.003). CONCLUSIONS & INFERENCES: Electroacupuncture at ST-36 improves gastric dysrhythmia and accelerates GE in rats with burns. The improvement seems to be mediated via the vagal pathway involving the inflammatory cytokine IL-6.

Colonic electrical stimulation: potential use for treatment of delayed colonic transit.

AIM: Recently there has been an increased interest in using electrical stimulation to regulate gut motility generally and particularly for the treatment of slow-transit constipation. In this preliminary canine study, we aimed to study the effects of colonic electrical stimulation (CES) on colonic motility and transit. METHOD: Nine dogs, each equipped with a pair of serosal colon electrodes and a proximal colon cannula were randomized to receive: (i) sham-CES, (ii) long pulse CES (20 cpm, 300 ms, 6 mA) or (iii) pulse train CES (40 Hz, 6 ms, 6 mA). Animals underwent assessment of colonic contractions via manometry, and of colonic transit by inserting 24 radiopaque markers via the colonic cannula and radiographically monitoring the markers at 2, 4 and 6 h following their insertion. The colonic transit was assessed by the geometric centre. RESULTS: We found that, compared with sham-CES, pulse train CES, but not long pulse CES, significantly increased the overall colonic motility index twofold and accelerated the colonic transit by 104% at 2 h, by 60% at 4 h and by 31% at 6 h (P = 0.01, P = 0.02 and P = 0.03 vs sham-CES at 2, 4 and 6 h, respectively). The accelerating effect of pulse train CES was found to be mediated via both cholinergic and nitrergic pathways. CONCLUSION: CES with pulse trains has prokinetic effects on colonic contractions and transit in healthy dogs, mediated via the cholinergic and nitrergic pathways. Further clinical studies are warranted to explore the therapeutic potential of CES for slow colonic transit constipation.

Effects and possible mechanisms of acupuncture at ST36 on upper and lower abdominal symptoms induced by rectal distension in healthy volunteers.

Background acupuncture (AP) has been shown to have a therapeutic potential for gastrointestinal motility disorders. The aims of this study were to investigate the effects and possible mechanisms of acupuncture on postprandial upper and lower abdominal symptoms induced by rectal distension (RD). Twenty healthy volunteers were involved in a two-session study (AP and sham-AP, AP and no-AP, or sham-AP and no-AP). In 12 of the volunteers, RD was performed for 60 min in the postprandial state, and AP at ST36 or sham-AP was performed during the second 30-min period of RD. Gastric slow waves and heart rate variability (HRV) were recorded using the electrogastrogram and electrocardiogram, respectively. Upper and lower abdominal symptoms were scored during RD with AP and sham-AP. In five of the subjects, an additional experiment with two sessions (with AP and no-AP) was performed. In the remaining eight volunteers, the same experiment was performed with sham-AP and no-AP was performed. The results were, first, RD at an average volume of 171 ml induced upper and lower abdominal symptoms (P < 0.01). AP, but not sham-AP or no-AP, reduced both upper and lower abdominal symptoms (P < 0.05). Second, RD decreased the percentage of normal gastric slow waves (P < 0.05). AP improved gastric slow waves compared with sham-AP or no-AP (P < 0.05). Third, in the larger, but not smaller, sample size experiment, the vagal activity during the RD plus AP period was significantly higher than that during the RD alone period in the same session and the corresponding period with sham-AP or no-AP in other sessions (P < 0.05). Neither sham-AP nor no-AP showed any effects on vagal activity (P > 0.05). Finally, in the experiment with eight volunteers, neither sham-AP nor no-AP showed any effects on RD-induced impairment in gastric slow waves, abdominal symptoms, or vagal activity (P > 0.05). The conclusions are RD induces upper or lower abdominal symptoms and impairs gastric slow waves in healthy volunteers. AP at ST36 is able to improve upper and lower abdominal symptoms and impaired gastric slow waves induced by RD, possibly mediated via the vagal pathway.

Short pulse gastric electrical stimulation for cisplatin-induced emesis in dogs.

BACKGROUND: In a previous study, we investigated the ameliorating effect of gastric electrical stimulation (GES) with a single set of parameters on emesis and behaviors suggestive of nausea induced by cisplatin in dogs. The aim of this study was to investigate the effects of GES with different parameters on cisplatin-induced emesis in dogs. METHODS: Seven dogs implanted with gastric serosal electrodes were studied in six randomized sessions: one control session with cisplatin (2 mg kg(-1)) and five sessions with cisplatin plus GES of different parameters: GES-A: 14 Hz, 5 mA, 0.3 ms, 0.1 s on and 5 s off; GES-B: increased frequency and on-time; GES-C: increased frequency; GES-D: increased frequency and pulse width; and GES-E: increased frequency and amplitude. Gastric slow waves and emetic responses were recorded in each session. KEY RESULTS: (i) Cisplatin induced emetic responses and gastric dysrhythmia. The peak time of the emetic response was during the fourth hour after cisplatin. (ii) GES with appropriate parameters reduced cisplatin-induced emesis. The number of vomiting times during the 6 h after cisplatin was 7.0 ± 1.4 in the control, 4.7 ± 1.2 with GES-A (P = 0.179), 4.2 ± 1.2 with GES-B (P = 0.109), 7.0 ± 0.8 with GES-C (P = 0.928), 2.1 ± 0.3 with GES-D (P = 0.005) and 4.7 ± 1.5 with GES-E (P = 0.129). However, none of the GES parameters could improve gastric dysrhythmia. CONCLUSIONS & INFERENCES: Gastric electrical stimulation with appropriate parameters reduces cisplatin-induced emetic responses and behaviors suggestive of nausea in dogs. Among the tested parameters, GES with increased pulse width seems to produce better relief of cisplatin-induced emesis.

Impaired postprandial releases/syntheses of ghrelin and PYY(3-36) and blunted responses to exogenous ghrelin and PYY(3-36) in a rodent model of diet-induced obesity.

BACKGROUND AND AIM: This study investigated the effects of peripheral administration of ghrelin and PYY(3-36) on food intake and plasma and tissue fasting and postprandial ghrelin and PYY(3-36) levels in normal-weight (NW) and diet-induced-obese (DIO) rats. METHODS: In experiment one, NW and DIO rats received a single intraperitoneal injection of saline, PYY(3-36) or ghrelin; food intake was measured for 4 h. In experiment two, total plasma ghrelin and PYY(3-36), gastric fundus ghrelin, and ascending colon PYY(3-36) were measured either after a 20-h fast or 2 h after refeeding in NW and DIO rats by radioimmunoassay. RESULTS: Compared to the NW rats, findings in the DIO rats revealed: (i) a reduced sensitivity to both the anorectic effect of exogenous PYY(3-36) and the orexigenic effect of exogenous ghrelin; (ii) the postprandial plasma ghrelin levels were significantly higher; and (iii) refeeding decreased endogenous plasma ghrelin levels by 53% in the NW rats and 39% in DIO rats. Refeeding increased the plasma PYY(3-36) level by 58% in the NW rats versus 9% in the DIO rats (P=0.003). CONCLUSIONS: Compared with regular rats, DIO rats exhibit blunted responses in food intake to exogenous ghrelin and PYY(3-36). Although endogenous ghrelin and PYY(3-36) in DIO rats are not altered in the fasting state, their responses to food ingestion are blunted in comparison with regular rats.

Effects and mechanisms of electroacupuncture on glucagon-induced small intestinal hypomotility in dogs.

BACKGROUND: Little is known on the effect of electroacupuncture (EA) (Br Med J, 2, 1976, 1225) on intestinal motility. The aim of this study was to investigate effects and mechanisms of EA on small intestinal contractions, transit, and slow waves in dogs. METHODS: Six dogs were equipped with two intestinal cannulas for the measurement of small intestinal contractions and transit. Glucagon was used to induce postprandial intestinal hypomotility. Each dog was studied in five randomized sessions: Control, glucagon, glucagon + EA, glucagon + EA + naloxone, and glucagon + EA + atropine. KEY RESULTS: 1 In the fasting state, EA induced intestinal contractions during motor quiescence (contractile index or CI: 4.4 ± 0.8 VS 8.3 ± 0.7, P < 0.05). 2 In the fed state, EA improved glucagon-induced intestinal hypomotility (CI: 3.8 ± 0.4 VS 6.1 ± 0.6, P < 0.05). 3 Electroacupuncture accelerated intestinal transit delayed by glucagon (67.9 ± 4.3 VS 40.2 ± 5.0 min, P < 0.05). 4 There was a negative correlation between the CI and the total transit time (R(2) = 0.59, P < 0.05). 5 The excitatory effect of EA was blocked by naloxone and partially blocked by atropine. 6 The percentage of normal slow waves was reduced with glucagon (70 ± 2%VS 98 ± 1% at baseline, P = 0.0015). Electroacupuncture normalized impaired slow waves and the effect was blocked by naloxone. CONCLUSIONS & INFERENCES: Electroacupuncture enhances intestinal contractions during Phase I of the migrating motor complex and glucagon-induced hypomotility in the fed state, and accelerates intestinal transit via the opioid and cholinergic pathways in dogs. Electroacupuncture may have a therapeutic potential for intestinal hypomotility.

Hepatic electrical stimulation reduces blood glucose in diabetic rats.

BACKGROUND: The aim of this study was to investigate the feasibility and mechanisms of controlling blood glucose using hepatic electrical stimulation (HES). METHODS: The study was performed in regular Sprague-Dawley (SD) rats, streptozotocin-induced type 1 diabetic rats and Zucker diabetic fatty (ZDF) rats chronically implanted with one pair of stimulation electrodes on two lobes of the liver tissues. KEY RESULTS: (i) Hepatic electrical stimulation was effective in reducing blood glucose by 27%-31% at time points 60, 75 and 90 min after oral glucose in normal rats; (ii) HES reduced blood glucose in both fasting and fed states in both type 1 and type 2 diabetic rats; (iii) Chronic HES decreased the blood glucose level, and, delayed gastric empty and increased plasma glucagon-like peptide-1 (GLP-1) level; and (iv) No adverse events were noted in any rats during HES. Histopathological analyses and liver function tests revealed no electrode dislodgement, tissue damages or liver enzyme changes with HES. CONCLUSIONS & INFERENCES: Hepatic electrical stimulation is capable of reducing both fasting and fed blood glucose in normal, and type 1 and type 2 diabetic rats and the effect may be partially mediated via an increase in GLP-1 release.

Ameliorating effects of mirtazapine on visceral hypersensitivity in rats with neonatal colon sensitivity.

BACKGROUND: The aim was to investigate the effects of mirtazapine on visceral hypersensitivity and gastric emptying in an established rodent model of colonic sensitization. METHODS: Twenty colonic sensitized rats and 20 matched controls were used. Visceral sensitivity during colorectal distension (CRD) was assessed by the measurement of abdominal electromyogram (EMG) with the pressures of 20, 40, and 60 mmHg. Mirtazapine with doses of 1, 5, and 10 mg kg(-1) were administered orally. Gastric emptying and small intestinal transit were performed in a separated experiment after gavage of 1.5 mL of phenol red solution. KEY RESULTS: (i) Visceral hypersensitivity after neonatal colonic sensitization was confirmed. (ii) Mirtazapine dose-dependently reduced visceral hypersensitivity in the colonic sensitized rats. The increases in EMG during CRD at 40, 60 mmHg were, 17.59 +/- 6.49 and 26.04 +/- 8.30, respectively, with saline session, and substantially reduced to 10.0 +/- 5.95 (P = 0.02 vs corresponding saline) and 12.58 +/- 7.43 (P < 0.001 vs saline) with mirtazapine at 10 mg kg(-1). Similar findings were noted at doses of 5 and 1 mg kg(-1) at a lesser degree. In the control rats, mirtazapine-reduced visceral sensitivity only during CRD at 60 mmHg. (iii) Mirtazapine 10 mg kg(-1) significantly accelerated gastric emptying (P = 0.045) but slightly and marginally delayed intestinal transit (P = 0.058) the colonic sensitized rats. CONCLUSIONS & INFERENCES: Mirtazapine dose-dependently ameliorates visceral hypersensitivity in colonic sensitized rats. Mirtazapine at a high dose improves delayed gastric emptying in colonic sensitized rats but slightly and marginally delays small intestinal transit. Its roles in altering gastrointestinal motility need further investigation.