Autonomic and cytokine mechanisms of acute electroacupuncture in a rodent model of functional dyspepsia.

BACKGROUND: Cytokines have been presumed to play an important role in the pathophysiology of functional dyspepsia (FD). Electroacupuncture (EA) has been used for FD treatment; however, its mechanisms remain largely unknown. This study aimed to (1) compare the plasma levels of cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10, in "FD" rats with normal control rats; (2) investigate whether EA, using chronically implanted electrodes, could inhibit the release of these cytokines; and (3) explore the correlation of cytokine levels with plasma norepinephrine (NE) levels and gastric emptying (GE). METHODS: A rodent model of FD was established via neonatal treatment with intragastric iodoacetamide. After 8 weeks, the rats were implanted with electrodes at acupoint ST36 for EA. The plasma levels of cytokines and NE were measured using enzyme-linked immunosorbent assay. We explored the correlations of cytokine levels with NE levels and GE. KEY RESULTS: (i) "FD" rats demonstrated increased levels of TNF-α, IL-1ß, and IL-6 (p < 0.05 each) compared with the control rats. (ii) EA significantly decreased the plasma levels of TNF-α, IL-1ß, and IL-6 in "FD" rats (p < 0.05 each) compared with sham EA. (iii) The plasma levels of NE were positively correlated with those of IL-6 (r = 0.86, p < 0.05) and IL-1ß (r = 0.81, p < 0.05), whereas NE levels and GE were negatively correlated with IL-10 levels (r = -0.870, p < 0.05 and r = -0.791, p < 0.05, respectively). CONCLUSIONS: EA inhibits the release of proinflammatory cytokines probably via the suppression of sympathetic activity in "FD" rats.

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.

Sacral nerve stimulation ameliorates colonic barrier functions in a rodent model of colitis.

BACKGROUND: The mucosal barrier damage is recognized as one of the key factors in the pathogenesis of colitis. While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown. METHODS: In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham-SNS for 10 days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight-junction proteins involved in regulating permeability and the FITC-dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system. KEY RESULTS: SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro-inflammatory cytokines (TNF-α, IL-6). SNS increased the expression of Zonula Occludens-1, Occludin, Claudin-1, and Junctional adhesion molecule-A in the colon tissue. The FITC-dextran test showed that the colonic permeability was lower with SCS than sham-SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub-P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity. CONCLUSIONS & INFERENCES: SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.

A novel method of sacral nerve stimulation for colonic inflammation.

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.

Sacral nerve stimulation with appropriate parameters improves constipation in rats by enhancing colon motility mediated via the autonomic-cholinergic mechanisms.

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit (P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity (P = 0.035) and decreased sympathetic activity (P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function.NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.

Sacral nerve stimulation improves colonic inflammation mediated by autonomic-inflammatory cytokine mechanism in rats.

BACKGROUND: Vagal nerve stimulation (VNS) was reported to have a therapeutic potential for inflammatory bowel disease (IBD). This study was designed to determine effects and mechanisms of SNS on colonic inflammation of in rodent models of IBD and compare the difference among SNS, VNS, and SNS plus VNS. METHODS: Intestinal inflammation in rats was induced by intrarectal administration of TNBS (2,4,6-Trinitrobenzenesulfonic acid) on the first day. Five days after intrarectal TNBS, the rats were treated with sham-VNS, VNS, Sham-SNS, SNS, and SNS + VNS for 10 days. In another experiment, after 10 days of 4% DSS (dextran sodium sulfate) in drinking water, rats were treated with 10-day sham-SNS and SNS. Various inflammatory responses were assessed; mechanisms involving autonomic functions and inflammatory cytokines were investigated. KEY RESULTS: (a) VNS, SNS, and VNS + SNS significantly and equally decreased the disease activity index and macroscopic scores, and normalized colon length; (b) IL-10 was decreased by TNBS but increased with SNS, VNS, and SNS + VNS; pro-inflammatory cytokines, IL-6, IL-17A, MCP-1 and TNF-α, were increased by TNBS but decreased with SNS, VNS, and SNS + VNS (P < .05); MPO activity was decreased by SNS, VNS, and SNS + VNS; (c) SNS, VNS, and SNS + VNS remarkably increased vagal activity that was suppressed by TNBS (P < .05); (d) smilar SNS effects were noted in rats with DSS-induced colitis. CONCLUSIONS & INFERENCES: SNS presents similar anti-inflammatory effects as VNS by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the autonomic pathway. Similar to VNS, SNS may also have a therapeutic potential for colonic inflammation.

Autonomically mediated anti-inflammatory effects of electrical stimulation at acupoints in a rodent model of colonic inflammation.

BACKGROUND: Acupuncture has been widely accepted for treatments of many diseases. This study was performed to determine effects and mechanisms of electroacupuncture (EA) by chronically implanted electrodes at acupoint ST36 on colonic inflammation induced by TNBS in rats. METHODS: After intrarectal administration of TNBS, the rats were treated with sham-EA, EA1/EA2 (two sets of parameters) for 3 weeks. Disease activity index (DAI), macroscopic and microscopic lesions, plasma levels of TNF-α, IL-1ß and IL-6 were observed as evaluation of inflammatory responses. The autonomic function was assessed by analysis of the heart rate variability. RESULTS: (a) Vagal activity was significantly increased with both acute and chronic EA1/EA2; (b) DAI was significantly decreased with both chronic EA1 and EA2, and EA2 was more potent than EA1 (P < 0.05); (c) The macroscopic score was 6.4 ± 0.6 with sham-EA and reduced to 4.9 ± 0.1 with EA1 (P < 0.05) and 4.0 ± 0.2 with EA2 (all P < 0.05). The histological score was 4.05 ± 0.58 with sham-EA and remained unchanged (3.71 ± 0.28) with EA1 (P > 0.05) but reduced to 3.0 ± 0.3 with EA2 (P < 0.01); (d) The plasma levels of TNF-α, IL-1ß and IL-6 were significantly decreased with EA2. CONCLUSIONS: Electrical stimulation at ST36 improves colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines via the autonomic mechanism.

Ameliorating Effects of Electroacupuncture on Dysmotility, Inflammation, and Pain Mediated via the Autonomic Mechanism in a Rat Model of Postoperative Ileus.

BACKGROUND/AIMS: Postoperative ileus increases healthcare costs and reduces the postoperative quality of life (QOL). The aim of this study is to investigate effects and mechanisms of electroacupuncture (EA) at ST36 and PC6 on gastrointestinal motility in rat model of postoperative ileus. METHODS: Laparotomy was performed in 24 rats (control [n = 8], sham-EA [n = 8], and EA [n = 8]) for the implantation of electrodes in the stomach and mid-jejunum for recording of gastric and small intestinal slow waves. Electrodes were placed in the chest skin for electrocardiogram (ECG). Intestinal manipulation (IM) was performed in Sham-EA and EA rats after surgical procedures. Small intestinal transit (SIT), gastric emptying (GE), postoperative pain, and plasma TNF-α were evaluated in all rats. RESULTS: (1) Compared with sham-EA, EA accelerated both SIT (P < 0.05) and GE (P < 0.05) and improved regularity of small intestinal slow waves. (2) Compared with the control rats (no IM), IM suppressed vagal activity and increased sympathovagal ratio assessed by the spectral analysis of heart rate variability from ECG, which were significantly prevented by EA. (3) EA significantly reduced pain score at 120 minutes (P < 0.05, vs 15 minutes) after the surgery, which was not seen with sham-EA. (4) Plasma TNF-α was increased by IM (P = 0.02) but suppressed by EA (P = 0.04) but not sham-EA. CONCLUSION: The postoperative ileus induced by IM, EA at ST36 and PC6 exerts a prokinetic effect on SIT and GE, a regulatory effect on small intestinal slow waves and an analgesic effect on postoperative pain possibly mediated via the autonomic-cytokine mechanisms.

Electroacupuncture via chronically implanted electrodes improves gastrointestinal motility by balancing sympathovagal activities in a rat model of constipation.

Electroacupuncture (EA) has been reported for treating constipation in clinical studies. However, little is known of the possible mechanisms involved in the prokinetic effect of EA. The aim of this study was to investigate the effects and underlying autonomic mechanisms of EA via chronically implanted electrodes for constipation in rat induced by Loperamide (Lop). Lop was given to regular rats to induce constipation. EA was performed via a pair of electrodes chronically implanted at bilateral acupoint ST-36. Feces characteristics, gastric emptying, small intestinal transit, distal colon transit time (dCTT), and whole gut transit time (WGTT) were measured in various sessions with EA or sham EA in rats with constipation induced by Lop. Heart rate variability (HRV) derived from the electrocardiogram was analyzed to evaluate autonomic functions. The number of fecal pellets was reduced by 27% with Lop (P < 0.01) and normalized by 7-day EA. Similar results were also observed in pellet weight. In normal rats compared with sham EA, EA shortened dCTT by 74% (P < 0.05 vs. sham EA), increased small intestinal transit by 28% (P < 0.01) and gastric emptying by 27% (P < 0.05), and accelerated whole gut transit by 14% (P < 0.05). In Lop-treated rats, the dCTT and WGTT were prolonged by Lop and normalized by EA. Lop significantly decreased vagal activity and increased sympathetic nerve activity; however, EA reversed these effects. EA at ST-36 via chronically implanted electrodes improves Lop-induced constipation by enhancing GI motility via the autonomic mechanisms. NEW & NOTEWORTHY The findings of the present study suggest that the proposed electroacupuncture (EA) may have great therapeutic potential for treating patients with opioid-induced constipation. It was demonstrated that EA at ST-36 improved transit of every organ along the gut mediated via the autonomic mechanisms in normal rats and rats with Lop-induced constipation. It is advised to administrate EA daily instead of two or three times weekly as reported in most of the clinical studies.

Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic ß cells in type 2 diabetic Goto-Kakizaki rats.

BACKGROUND/OBJECTIVE: Recently, intestinal electrical stimulation (IES) has been reported to result in weight loss; however, it is unclear whether it has a therapeutic potential for diabetes. The aim of the present study was to explore the potential hypoglycemic effects of IES and its possible mechanisms involving ß cells in diabetic rats. SUBJECTS/METHODS: Diabetic Goto-Kakizaki (GK) rats were chronically implanted with one pair of electrodes in the duodenum. The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed with or without IES, and plasma glucagon-like peptide-1 (GLP-1) and insulin level were measured. In the other two OGTT sessions, rats were treated with either Exendin (9-39) (GLP-1 antagonist) or Exendin (9-39) plus IES to investigate the underlying mechanism involving GLP-1. Gastric emptying and small intestinal transit were also measured with or without IES. In a chronic study, GK rats were treated with IES or Sham-IES for 8 weeks. Blood glucose, plasma GLP-1 and insulin level, body weight, and food intake were measured. Pancreas weight, islet ß-cell apoptosis, and proliferation were also analyzed. RESULTS: Acute IES reduced blood glucose level from 60 to 120 min during OGTT by 16-20% (all p < 0.05, vs. Sham-IES). GLP-1 antagonist significantly blocked the inhibitory effect of IES on hyperglycemia from 15 to 120 min (all p < 0.05). IES accelerated the small intestinal transit by 15% (p = 0.004). After 8 weeks of chronic stimulation, IES significantly reduced blood glucose (p < 0.05) and body weight (p = 0.02) and increased the plasma GLP-1 concentration (p < 0.05). Furthermore, we observed that chronic IES reduced pancreatic ß-cell apoptosis (p = 0.045), but showed no effects on ß-cell proliferation. CONCLUSIONS: Our study firstly proved the hypoglycemic effect of IES in a rodent model of type 2 diabetes, possibly attributed to the increasing GLP-1 secretion and improvement in ß-cell functions.

Ameliorating effects and mechanisms of chronic electroacupuncture at ST36 in a rodent model of dyspepsia induced by cisplatin.

BACKGROUND: Chemotherapy-associated dyspepsia syndrome (CADS) is among the most intensive side effects and critical concerns for patients with cancer. To investigate the effects and mechanisms of chronic electroacupuncture (EA) at ST36 on chemotherapy-associated dyspeptic symptoms (CADS) in rats. METHODS: Cisplatin (8 mg/kg, ip) was given once to establish CADS model. EA or sham-EA treatment was then performed one hour daily for 21 days. KEY RESULTS: (a) EA treatment decreased kaolin intake within 24 hours (1.67 ± 0.23 g vs 2.36 ± 0.37 g in sham-EA, P < 0.05); EA increased food intake (9.43 ± 2.28 vs 4.32 ± 1.26 in sham-EA, P < 0.05) and cisplatin-induced reduction of body weight (426.38 ± 13.25 vs 407.92 ± 13.26 in sham-EA, P = 0.05). (b) The incidence of normal behavioral satiety sequence (53%) in EA group was greater than that in sham-EA (32%) group (X2  = 17.68, P < 0.01). (c) EA increased the percentage of normal gastric slow waves (82.6 ± 5.98 vs 22.8 ± 1.90 in sham-EA, P < 0.05). (d) EA normalized cisplatin delayed gastric emptying (71.3% ± 6.8% vs 44.6% ± 11.2% in control, P < 0.05). (e) EA decreased ratio of heart rate variability (0.30 ± 0.03 vs 0.56 ± 0.05 in sham-EA, P < 0.05). (f) EA decreased fasting ghrelin, glucagon-like peptide-1 and peptide YY (P < 0.01 vs sham-EA for all). CONCLUSIONS AND INFERENCES: Chronic EA ameliorates dyspepsia symptom and improves gastric dysmotility induced by Cisplatin, mediated via the vagal and gastrointestinal hormonal mechanisms.

Tea consumption is associated with cognitive impairment in older Chinese adults.

OBJECTIVE: To explore the association between tea consumption and cognitive impairment (CoI). METHODS: 4579 adults (≥60 years) from the Weitang Geratric Diseases Study were assessed for characteristics of tea consumption and cognitive function by administering questionnaires and the Abbreviated Mental Test (AMT), respectively. We divided the subjects into normal cognitive function group (AMT score ≥8) and CoI group (AMT score ≤7).   The association between tea consumption and risk of CoI was determined by logistic regression models. RESULTS: The least-squared means of the AMT scores for the subjects who seldom consumed tea were less favorable than those who habitually consumed tea. An inverse association was found between tea consumption (of any type) and prevalence of CoI (odds ratio = 0.74, 95% confidence interval = 0.57-0.98, P = 0.032). Interestingly, the protective correlation of tea was more obvious in never smokers (odds ratio = 0.63), but vanished in current/former smokers (odds ratio = 1.10). In never smokers, frequency of tea consumption was significantly associated with CoI (P for trend = 0.010). CONCLUSION: Habitual tea consumption is suggested to be associated with a decreased risk of CoI among elders in Suzhou, and a higher frequency of tea consumption was associated with a lower prevalence of CoI among never smokers.

An Optimized IES Method and Its Inhibitory Effects and Mechanisms on Food Intake and Body Weight in Diet-Induced Obese Rats: IES for Obesity.

PURPOSE: This paper aims to optimize stimulation parameters and durations for intestinal electrical stimulation (IES) and to explore the effects and mechanisms of chronic IES with optimized methodology in obesity rats. MATERIALS AND METHODS: Sixteen diet-induced obese (DIO) rats were tested for food intake with four different sets of IES parameters each lasting 1 week. Then, another 12 DIO rats were used to test the effect of IES on food intake with different stimulation durations. Finally, 16 DIO rats were treated with IES or sham-IES for 4 weeks. Meal patterns, food intake, and body weight were observed. Mechanisms involving gastrointestinal motility, ghrelin, and glucagon-like peptide-1 (GLP-1) were studied. RESULTS: (1) Acute IES with different parameters showed different inhibitory effects on food intake, and the most effective parameters were 0.6 s on, 0.9 s off, 80 Hz, 2 ms, and 4 mA with which 26.3% decrease in food intake was noted (p < 0.001). (2) IES with daily treatment of 12 h was most effective in suppressing food intake compared with 1 or 6 h. (3) Four-week IES reduced net weight by 10.9% (p < 0.05 vs. sham-IES) and epididymal fat pad weight by 13.9% (p < 0.001). (4) IES delayed gastric emptying (p < 0.001) and accelerated intestinal transit (p < 0.05). (5) IES increased both fasting and postprandial plasma levels of GLP-1 but not ghrelin. CONCLUSION: Twelve-hour daily IES using optimized stimulation parameters reduces food intake and body weight in DIO rats by altering gastrointestinal motility and GLP-1. The IES methodology derived in this study may have a therapeutic potential for obesity.

Anti-inflammatory effects and mechanisms of vagal nerve stimulation combined with electroacupuncture in a rodent model of TNBS-induced colitis.

The purpose of this study was to determine the effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-trinitrobenzenesulfonic acid). The rats were then treated with sham ES (electrical stimulation), VNS, or VNS + EA for 3 wk. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, plasma levels of TNFα, IL-1ß, and IL-6, and myeloperoxidase (MPO) activity of colonic tissues. The autonomic function was assessed by the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. It was found that 1) the area under curve (AUC) of DAI was substantially decreased with VNS + EA and VNS, with VNS + EA being more effective than VNS (P < 0.001); 2) the macroscopic score was 6.43 ± 0.61 in the sham ES group and reduced to 1.86 ± 0.26 with VNS (P < 0.001) and 1.29 ± 0.18 with VNS + EA (P < 0.001); 3) the histological score was 4.05 ± 0.58 in the sham ES group and reduced to 1.93 ± 0.37 with VNS (P < 0.001) and 1.36 ± 0.20 with VNS + EA (P < 0.001); 4) the plasma levels of TNFα, IL-1ß, IL-6, and MPO were all significantly decreased with VNS and VNS + EA compared with the sham ES group; and 5) autonomically, both VNS + EA and VNS substantially increased vagal activity and decreased sympathetic activity compared with sham EA (P < 0.001, P < 0.001, respectively). In conclusion, chronic VNS improves inflammation in TNBS-treated rats by inhibiting proinflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS.NEW & NOTEWORTHY This is the first study to address and compare the effects of vagal nerve stimulation (VNS), electrical acupuncture (EA) and VNS + EA on TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced colitis in rats. The proposed chronic VNS + EA, VNS, and EA were shown to decrease DAI and ameliorate macroscopic and microscopic damages in rats with TNBS-induced colitis via the autonomic pathway. The addition of EA to VNS provided a significant effect on the behavioral assessment of inflammation (DAI, CMDI, and histological score) but not on cytokines or mechanistic measurements, suggesting an overall systemic effect of EA.View this article's corresponding video summary at https://youtu.be/-rEz6HMkErM.

Inhibitory Effects and Mechanisms of Electroacupuncture via Chronically Implanted Electrodes on Stress-Induced Gastric Hypersensitivity in Rats With Neonatal Treatment of Iodoacetamide.

BACKGROUND: Stress is considered an independent factor causing and aggravating gastrointestinal symptoms, including visceral pain. The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on stress-induced gastric hypersensitivity in rats treated with neonatal iodoacetamide mimicking human functional dyspepsia (FD). METHODS: Neonatal rats were treated with gavage of 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily for six days starting on tenth day after birth. The control group was given 0.2 mL of 2% sucrose. When the rats were eight weeks old, acute restraint stress was performed on them for 90 min. EA at ST36 (ZuSanLi) was performed during the acute stress or 30 min after the stress. Adrenoceptor blocking drugs (propranolol and phentolamine) were injected intraperitoneally 30 min before acute restraint stress to explore possible sympathetic mechanisms. Visceral-motor responses to gastric distention were assessed by electromyogram (EMG). RESULTS: 1) Stress-induced gastric hypersensitivity was significantly more severe in the FD rats, compared to the control rats. It was blocked by the adrenoceptor antagonists. 2) EA inhibited stress-induced gastric hypersensitivity; the preventive effect of EA (given during stress) was more remarkable than the curative effect (given after stress). Stress resulted in a higher sympathovagal ratio and this was suppressed by EA. CONCLUSIONS: Rats treated with neonatal iodoacetamide mimicking FD are more vulnerable to stress. Stress-induced gastric hypersensitivity can be prevented or suppressed by EA at ST36 via the restoration of sympathovagal balance.

Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD. METHODS: Ten-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the "stomach" point with different parameters or sham-EA was performed on 8-week-old animals. Gastric sensitivity to gastric distention was measured under different conditions. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. Naloxone was injected intraperitoneally before AEA to explore the opioid mechanism. Gastric emptying was measured at the end of the study. RESULTS: 1) Gastric sensitivity to gastric distention was higher in the FD rats. AEA with parameters of 0.1s on, 0.4s off, 100Hz, 0.3ms and 0.4-0.5mA, but not other parameters or sham-EA, decreased gastric hypersensitivity in the FD rats. Naloxone did not block the effect of AEA. 2) Lower vagal activity and higher sympathovagal ratio were noted in the FD rats, compared with the controls. AEA increased vagal activity and improved sympathovagal imbalance. CONCLUSIONS: AEA ameliorates gastric hypersensitivity in FD rats and this effect may be attributed to the improvement of sympathovagal balance.

Electrical therapies for gastrointestinal motility disorders.

INTRODUCTION: Gastrointestinal (GI) motility disorders are common in clinical settings, including esophageal motility disorders, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, post-operative ileus, irritable bowel syndrome, diarrhea and constipation. While a number of drugs have been developed for treating GI motility disorders, few are currently available. Emerging electrical stimulation methods may provide new treatment options for these GI motility disorders. Areas covered: This review gives an overview of electrical therapies that have been, and are being developed for GI motility disorders, including gastroesophageal reflux, functional dyspepsia, gastroparesis, intestinal motility disorders and constipation. Various methods of gastrointestinal electrical stimulation are introduced. A few methods of nerve stimulation have also been described, including spinal cord stimulation and sacral nerve stimulation. Potentials of electrical therapies for obesity are also discussed. PubMed was searched using keywords and their combinations: electrical stimulation, spinal cord stimulation, sacral nerve stimulation, gastrointestinal motility and functional gastrointestinal diseases. Expert commentary: Electrical stimulation is an area of great interest and has potential for treating GI motility disorders. However, further development in technologies (devices suitable for GI stimulation) and extensive clinical research are needed to advance the field and bring electrical therapies to bedside.

Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects.

BACKGROUND: Impaired gastric accommodation is recognized as one of major pathophysiologies in functional dyspepsia and gastroparesis. Electroacupuncture has been shown to improve gastric accommodation in laboratory settings. It is, however, unknown whether it exerts similar ameliorating effect in humans and whether needleless transcutaneous electroacupuncture (TEA) is also effective in improving gastric accommodation. AIM: The aim was to investigate the effects of TEA on gastric accommodation, gastric slow waves, and dyspeptic related symptoms. METHODS: Thirteen healthy volunteers were studied in four randomized sessions: control, cold nutrient liquid, cold nutrient liquid + sham-TEA, and cold nutrient liquid + TEA. The subjects were requested to drink Ensure until reaching maximum satiety. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded to assess the gastric and autonomic functions respectively. RESULTS: 1) Gastric accommodation was reduced with the cold drink in comparison with the warm drink (P = 0.023). TEA improved the impaired gastric accommodation from 539.2 ± 133.8 ml to 731.0 ± 185.7 ml (P = 0.005). 2) The percentage of normal gastric slow waves in six subjects was significantly decreased in the cold session (P = 0.002) and improved in the TEA session (P = 0.009 vs sham; P < 0.001 vs cold). 3) TEA showed significant improvement in the bloating (80.8 ± 5.7 vs 61.2 ± 26.2, P = 0.011), postprandial fullness (48.1 ± 12.0 vs 34.2 ± 21.2, P = 0.042), and nausea (29.6 ± 10.9 vs 19.2 ± 11.2, P = 0.026) in comparison with sham-TEA session. 4) Neither cold drink nor TEA altered vagal activities (P > 0.05). CONCLUSIONS: TEA improves impaired gastric accommodation and slow waves induced by cold drink and the effect does not seem to be mediated via the vagal mechanisms.