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1
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Leinen M, Grandy EF, Gebel LMU, Santana TM, Rodriguez AL, Singh SK, Fernandez MI, Dalugdug JC, Garcia-Colon EM, Lybeshari K, Alexander DR, Maura MI, Gonzalez MDC, De Paula Cunha Almeida C, Anyaso-Samuel S, Datta S, Schiefer MA. Bilateral Subdiaphragmatic Vagal Nerve Stimulation Using a Novel Waveform Decreases Body Weight, Food Consumption, Adiposity, and Activity in Obesity-Prone Rats. Obes Surg 2024; 34:1-14. [PMID: 38040984 PMCID: PMC10781827 DOI: 10.1007/s11695-023-06957-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 11/05/2023] [Accepted: 11/13/2023] [Indexed: 12/03/2023]
Abstract
INTRODUCTION Obesity affects millions of Americans. The vagal nerves convey the degree of stomach fullness to the brain via afferent visceral fibers. Studies have found that vagal nerve stimulation (VNS) promotes reduced food intake, causes weight loss, and reduces cravings and appetite. METHODS Here, we evaluate the efficacy of a novel stimulus waveform applied bilaterally to the subdiaphragmatic vagal nerve stimulation (sVNS) for almost 13 weeks. A stimulating cuff electrode was implanted in obesity-prone Sprague Dawley rats maintained on a high-fat diet. Body weight, food consumption, and daily movement were tracked over time and compared against three control groups: sham rats on a high-fat diet that were implanted with non-operational cuffs, rats on a high-fat diet that were not implanted, and rats on a standard diet that were not implanted. RESULTS Results showed that rats on a high-fat diet that received sVNS attained a similar weight to rats on a standard diet due primarily to a reduction in daily caloric intake. Rats on a high-fat diet that received sVNS had significantly less body fat than other high-fat controls. Rats receiving sVNS also began moving a similar amount to rats on the standard diet. CONCLUSION Results from this study suggest that bilateral subdiaphragmatic vagal nerve stimulation can alter the rate of growth of rats maintained on a high-fat diet through a reduction in daily caloric intake, returning their body weight to that which is similar to rats on a standard diet over approximately 13 weeks.
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Affiliation(s)
- Monique Leinen
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Elise F Grandy
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Lourdes M Ubeira Gebel
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Tahimi Machin Santana
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Amanda L Rodriguez
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Sundip K Singh
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Michael I Fernandez
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Justin C Dalugdug
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Elaine M Garcia-Colon
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Kamela Lybeshari
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Daniel R Alexander
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Maria I Maura
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | - Maria D Cabrera Gonzalez
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA
| | | | - Samuel Anyaso-Samuel
- Department of Biostatistics, University of Florida, 2004 Mowry Rd, 5Th Fl, Gainesville, FL, 32603, USA
| | - Somnath Datta
- Department of Biostatistics, University of Florida, 2004 Mowry Rd, 5Th Fl, Gainesville, FL, 32603, USA
| | - Matthew A Schiefer
- Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, 1601 SW Archer Rd, Gainesville, FL, 32608, USA.
- Department of Biomedical Engineering, University of Florida, 1275 Center Dr, Gainesville, FL, 32611, USA.
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Bertoli D, Mark EB, Liao D, Okdahl T, Nauser S, Daugberg LH, Brock C, Brock B, Knop FK, Krogh K, Brøndum Frøkjær J, Drewes AM. MRI-Based Quantification of Pan-Alimentary Function and Motility in Subjects with Diabetes and Gastrointestinal Symptoms. J Clin Med 2023; 12:5968. [PMID: 37762909 PMCID: PMC10532375 DOI: 10.3390/jcm12185968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/09/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Background: Diabetes-induced gastrointestinal (GI) symptoms are common but difficult to correctly diagnose and manage. We used multi-segmental magnetic resonance imaging (MRI) to evaluate structural and functional GI parameters in diabetic patients and to study the association with their symptomatic presentation. Methods: Eighty-six participants (46 with diabetes and GI symptoms, 40 healthy controls) underwent baseline and post-meal MRI scans at multiple timepoints. Questionnaires were collected at inclusion and following the scans. Data were collected from the stomach, small bowel, and colon. Associations between symptoms and collected data were explored. Utilizing machine learning, we determined which features differentiated the two groups the most. Key Results: The patient group reported more symptoms at inclusion and during MRI scans. They showed 34% higher stomach volume at baseline, 40% larger small bowel volume, 30% smaller colon volume, and less small bowel motility postprandially. They also showed positive associations between gastric volume and satiety scores, gastric emptying time and reflux scores, and small bowel motility and constipation scores. No differences in gastric emptying were observed. Small bowel volume and motility were used as inputs to a classification tool that separated patients and controls with 76% accuracy. Conclusions: In this work, we studied structural and functional differences between patients with diabetes and GI symptoms and healthy controls and observed differences in stomach, small bowel, and colon volumes, as well as an adynamic small bowel in patients with diabetes and GI symptoms. Associations between recorded parameters and perceived symptoms were also explored and discussed.
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Affiliation(s)
- Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
- Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark;
| | - Esben Bolvig Mark
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
| | - Donghua Liao
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
| | - Tina Okdahl
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
| | - Serena Nauser
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
| | - Louise Hostrup Daugberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
- Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark;
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
| | - Birgitte Brock
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1353 Copenhagen, Denmark; (B.B.); (F.K.K.)
| | - Filip Krag Knop
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1353 Copenhagen, Denmark; (B.B.); (F.K.K.)
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark
- Clinical Research, Steno Diabetes Center Copenhagen, 2730 Herlev, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark;
- Steno Diabetes Center Aarhus, 8200 Aarhus, Denmark
| | - Jens Brøndum Frøkjær
- Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark;
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; (D.B.); (E.B.M.); (D.L.); (T.O.); (S.N.); (L.H.D.); (C.B.)
- Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark;
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
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Perley A, Roustaei M, Aguilar-Rivera M, Kunkel DC, Hsiai TK, Coleman TP, Abiri P. Miniaturized wireless gastric pacing via inductive power transfer with non-invasive monitoring using cutaneous Electrogastrography. Bioelectron Med 2021; 7:12. [PMID: 34425917 PMCID: PMC8383397 DOI: 10.1186/s42234-021-00074-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 07/12/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gastroparesis is a debilitating disease that is often refractory to pharmacotherapy. While gastric electrical stimulation has been studied as a potential treatment, current devices are limited by surgical complications and an incomplete understanding of the mechanism by which electrical stimulation affects physiology. METHODS A leadless inductively-powered pacemaker was implanted on the gastric serosa in an anesthetized pig. Wireless pacing was performed at transmitter-to-receiver distances up to 20 mm, frequency of 0.05 Hz, and pulse width of 400 ms. Electrogastrogram (EGG) recordings using cutaneous and serosal electrode arrays were analyzed to compute spectral and spatial statistical parameters associated with the slow wave. RESULTS Our data demonstrated evident change in EGG signal patterns upon initiation of pacing. A buffer period was noted before a pattern of entrainment appeared with consistent and low variability in slow wave direction. A spectral power increase in the EGG frequency band during entrainment also suggested that pacing increased strength of the slow wave. CONCLUSION Our preliminary in vivo study using wireless pacing and concurrent EGG recording established the foundations for a minimally invasive approach to understand and optimize the effect of pacing on gastric motor activity as a means to treat conditions of gastric dysmotility.
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Affiliation(s)
- Andrew Perley
- Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Mehrdad Roustaei
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Marcelo Aguilar-Rivera
- Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA
| | - David C Kunkel
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Tzung K Hsiai
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.,Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Todd P Coleman
- Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Parinaz Abiri
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA. .,Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
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4
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Loper H, Leinen M, Bassoff L, Sample J, Romero-Ortega M, Gustafson KJ, Taylor DM, Schiefer MA. Both high fat and high carbohydrate diets impair vagus nerve signaling of satiety. Sci Rep 2021; 11:10394. [PMID: 34001925 PMCID: PMC8128917 DOI: 10.1038/s41598-021-89465-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 04/26/2021] [Indexed: 11/23/2022] Open
Abstract
Obesity remains prevalent in the US. One potential treatment is vagus nerve stimulation (VNS), which activates the sensory afferents innervating the stomach that convey stomach volume and establish satiety. However, current VNS approaches and stimulus optimization could benefit from additional understanding of the underlying neural response to stomach distension. In this study, obesity-prone Sprague Dawley rats consumed a standard, high-carbohydrate, or high-fat diet for several months, leading to diet-induced obesity in the latter two groups. Under anesthesia, the neural activity in the vagus nerve was recorded with a penetrating microelectrode array while the stomach was distended with an implanted balloon. Vagal tone during distension was compared to baseline tone prior to distension. Responses were strongly correlated with stomach distension, but the sensitivity to distension was significantly lower in animals that had been fed the nonstandard diets. The results indicate that both high fat and high carbohydrate diets impair vagus activity.
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Affiliation(s)
- Hailley Loper
- Malcom Randall VA Medical Center, Gainesville, FL, USA.,Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA
| | - Monique Leinen
- Malcom Randall VA Medical Center, Gainesville, FL, USA.,Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA
| | - Logan Bassoff
- Malcom Randall VA Medical Center, Gainesville, FL, USA.,Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA
| | - Jack Sample
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.,College of Medicine & Life Sciences, University of Toledo, Toledo, OH, USA
| | - Mario Romero-Ortega
- Departments of Biomedical Engineering and Biomedical Sciences, University of Houston, Houston, TX, USA
| | - Kenneth J Gustafson
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.,Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Dawn M Taylor
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.,Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.,Department of Neurosciences, The Cleveland Clinic, Cleveland, OH, USA
| | - Matthew A Schiefer
- Malcom Randall VA Medical Center, Gainesville, FL, USA. .,Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA. .,Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
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5
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Gautron L. The Phantom Satiation Hypothesis of Bariatric Surgery. Front Neurosci 2021; 15:626085. [PMID: 33597843 PMCID: PMC7882491 DOI: 10.3389/fnins.2021.626085] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/06/2021] [Indexed: 01/26/2023] Open
Abstract
The excitation of vagal mechanoreceptors located in the stomach wall directly contributes to satiation. Thus, a loss of gastric innervation would normally be expected to result in abrogated satiation, hyperphagia, and unwanted weight gain. While Roux-en-Y-gastric bypass (RYGB) inevitably results in gastric denervation, paradoxically, bypassed subjects continue to experience satiation. Inspired by the literature in neurology on phantom limbs, I propose a new hypothesis in which damage to the stomach innervation during RYGB, including its vagal supply, leads to large-scale maladaptive changes in viscerosensory nerves and connected brain circuits. As a result, satiation may continue to arise, sometimes at exaggerated levels, even in subjects with a denervated or truncated stomach. The same maladaptive changes may also contribute to dysautonomia, unexplained pain, and new emotional responses to eating. I further revisit the metabolic benefits of bariatric surgery, with an emphasis on RYGB, in the light of this phantom satiation hypothesis.
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Affiliation(s)
- Laurent Gautron
- Department of Internal Medicine, Center for Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX, United States
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6
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Carrano FM, Peev MP, Saunders JK, Melis M, Tognoni V, Di Lorenzo N. The Role of Minimally Invasive and Endoscopic Technologies in Morbid Obesity Treatment: Review and Critical Appraisal of the Current Clinical Practice. Obes Surg 2019; 30:736-752. [DOI: 10.1007/s11695-019-04302-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Maisiyiti A, Chen JDZ. Systematic review on gastric electrical stimulation in obesity treatment. Expert Rev Med Devices 2019; 16:855-861. [PMID: 31570014 PMCID: PMC6946629 DOI: 10.1080/17434440.2019.1673728] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/24/2019] [Indexed: 12/16/2022]
Abstract
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.
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Affiliation(s)
- Alimujiang Maisiyiti
- Department of Minimally Invasive Surgery, Hernias and Abdominal Wall Surgery, People’s Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, 830001, China
| | - Jiande DZ Chen
- Division of Gastroenterology and Hepatology, University of Johns Hopkins School of Medicine, Baltimore, MD, USA
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8
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Payne SC, Furness JB, Stebbing MJ. Bioelectric neuromodulation for gastrointestinal disorders: effectiveness and mechanisms. Nat Rev Gastroenterol Hepatol 2019; 16:89-105. [PMID: 30390018 DOI: 10.1038/s41575-018-0078-6] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The gastrointestinal tract has extensive, surgically accessible nerve connections with the central nervous system. This provides the opportunity to exploit rapidly advancing methods of nerve stimulation to treat gastrointestinal disorders. Bioelectric neuromodulation technology has considerably advanced in the past decade, but sacral nerve stimulation for faecal incontinence currently remains the only neuromodulation protocol in general use for a gastrointestinal disorder. Treatment of other conditions, such as IBD, obesity, nausea and gastroparesis, has had variable success. That nerves modulate inflammation in the intestine is well established, but the anti-inflammatory effects of vagal nerve stimulation have only recently been discovered, and positive effects of this approach were seen in only some patients with Crohn's disease in a single trial. Pulses of high-frequency current applied to the vagus nerve have been used to block signalling from the stomach to the brain to reduce appetite with variable outcomes. Bioelectric neuromodulation has also been investigated for postoperative ileus, gastroparesis symptoms and constipation in animal models and some clinical trials. The clinical success of this bioelectric neuromodulation therapy might be enhanced through better knowledge of the targeted nerve pathways and their physiological and pathophysiological roles, optimizing stimulation protocols and determining which patients benefit most from this therapy.
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Affiliation(s)
- Sophie C Payne
- Bionics Institute, East Melbourne, Victoria, Australia. .,Medical Bionics Department, University of Melbourne, Parkville, Victoria, Australia.
| | - John B Furness
- Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.,Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
| | - Martin J Stebbing
- Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.,Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
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Wang R, Abukhalaf Z, Javan-Khoshkholgh A, Wang THH, Sathar S, Du P, Angeli TR, Cheng LK, O’Grady G, Paskaranandavadivel N, Farajidavar A. A Miniature Configurable Wireless System for Recording Gastric Electrophysiological Activity and Delivering High-Energy Electrical Stimulation. IEEE JOURNAL ON EMERGING AND SELECTED TOPICS IN CIRCUITS AND SYSTEMS 2018; 8:221-229. [PMID: 30687579 PMCID: PMC6345532 DOI: 10.1109/jetcas.2018.2812105] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
The purpose of this paper is to develop and validate a miniature system that can wirelessly acquire gastric electrical activity called slow waves, and deliver high energy electrical pulses to modulate its activity. The system is composed of a front-end unit, and an external stationary back-end unit that is connected to a computer. The front-end unit contains a recording module with three channels, and a single-channel stimulation module. Commercial off-the-shelf components were used to develop front- and back-end units. A graphical user interface was designed in LabVIEW to process and display the recorded data in real-time, and store the data for off-line analysis. The system was successfully validated on bench top and in vivo in porcine models. The bench-top studies showed an appropriate frequency response for analog conditioning and digitization resolution to acquire gastric slow waves. The system was able to deliver electrical pulses at amplitudes up to 10 mA to a load smaller than 880 Ω. Simultaneous acquisition of the slow waves from all three channels was demonstrated in vivo. The system was able to modulate –by either suppressing or entraining– the slow wave activity. This study reports the first high-energy stimulator that can be controlled wirelessly and integrated into a gastric bioelectrical activity monitoring system. The system can be used for treating functional gastrointestinal disorders.
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Affiliation(s)
- Rui Wang
- Integrated Medical Systems (IMS) Laboratory at the School of Engineering and Computing Sciences, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Zaid Abukhalaf
- Integrated Medical Systems (IMS) Laboratory at the School of Engineering and Computing Sciences, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Amir Javan-Khoshkholgh
- Integrated Medical Systems (IMS) Laboratory at the School of Engineering and Computing Sciences, New York Institute of Technology, Old Westbury, NY 11568, USA
| | - Tim H.-H. Wang
- Department of Surgery, University of Auckland, New Zealand
| | - Shameer Sathar
- Auckland Bioengineering Institute, University of Auckland, New Zealand
| | - Peng Du
- Auckland Bioengineering Institute, University of Auckland, New Zealand
| | - Timothy R. Angeli
- Auckland Bioengineering Institute, University of Auckland, New Zealand
| | - Leo K. Cheng
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Department of Surgery, Vanderbilt University, Nashville, TN, USA
| | - Greg O’Grady
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Department of Surgery, University of Auckland, New Zealand
| | - Niranchan Paskaranandavadivel
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Department of Surgery, University of Auckland, New Zealand
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10
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Insulin Resistance, Glucose Metabolism, Inflammation, and the Role of Neuromodulation as a Therapy for Type-2 Diabetes. Neuromodulation 2018. [DOI: 10.1016/b978-0-12-805353-9.00133-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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11
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Emerging Gastric Stimulation for Dysmotility Disorder and Obesity. Neuromodulation 2018. [DOI: 10.1016/b978-0-12-805353-9.00116-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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12
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Blasi C. The Role of the Vagal Nucleus Tractus Solitarius in the Therapeutic Effects of Obesity Surgery and Other Interventional Therapies on Type 2 Diabetes. Obes Surg 2016; 26:3045-3057. [DOI: 10.1007/s11695-016-2419-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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13
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Yan Y, Tian L, Xiang X, Ding W, Song G, Xu J. Chronic gastric electrical stimulation leads to weight loss via modulating multiple tissue neuropeptide Y, orexin, α-melanocyte-stimulating hormone and oxytocin in obese rats. Scand J Gastroenterol 2016. [PMID: 26199984 DOI: 10.3109/00365521.2015.1069391] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Gastric electrical stimulation (GES) has great potential for the treatment of obesity. We investigated the impact of chronic GES on the alteration of adipose tissue and the regulation of neuropeptide Y (NPY), orexin (OX), α-melanocyte-stimulating hormone (α-MSH) and oxytocin (OXT), and their receptors in several tissues. MATERIAL AND METHODS Most of the experiments included three groups of diet-induced obesity rats: (1) sham-GES (SGES); (2) GL-6mA (GES with 6 mA, 4 ms, 40 Hz, 2 s on, 3 s off at lesser curvature); and (3) SGES-PF (SGES rats receiving pair feeding to match the consumption of GL-6mA rats). Chronic GES was applied for 2 h every day for 4 weeks. During treatment with GES, food intake and body weight were monitored weekly. The alteration of epididymal fat weight, gastric emptying, and expression of peptides and their receptors in several tissues were determined. RESULTS GL-6mA was more potent than SGES-PF in decreasing body weight gain, epididymal fat tissue weight, adipocyte size and gastric emptying. Chronic GES significantly altered NPY, OX, α-MSH and OXT and their receptors in the hypothalamus, adipose tissue and stomach. CONCLUSIONS Chronic GES effectively leads to weight loss by reducing food intake, fat tissue weight and gastric emptying. NPY, α-MSH, orexin and OXT, and their receptors in the hypothalamus, adipose tissue and stomach appear to be involved in the anti-obesity effects of chronic GES.
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Affiliation(s)
- Yun Yan
- a 1 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China
| | - Lugao Tian
- a 1 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China
| | - Xuelian Xiang
- a 1 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China
| | - Wei Ding
- a 1 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China
| | - Gengqing Song
- b 2 Internal Medicine Department, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine , El Paso, TX, USA
| | - Junying Xu
- a 1 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China
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Abstract
Obesity is a growing health problem worldwide with a major impact on health and healthcare expenditures. Medical therapy in the form of diet and pharmacotherapy has limited effect on weight. Standard bariatric surgery is effective but is associated with morbidity and mortality, creating an unmet need for alternative therapies. One such therapy, the application of electrical stimulation to the stomach, has been studied extensively for the last two decades. Though pulse parameters differ between the various techniques used, the rationale behind this assumes that application of electrical current can interfere with gastric motor function or modulate afferent signaling to the brain or both. Initial studies led by industry failed to show an effect on body weight. However, more recently, there has been a renewed interest in this therapeutic modality with a number of concepts being evaluated in large human trials. If successful, this minimally invasive and low-risk intervention would be an important addition to the existing menu of therapies for obesity.
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Affiliation(s)
- Jenny D Chiu
- Department of Medicine, Division of Gastroenterology, Keck School of Medicine at USC, 1520 San Pablo Street, Los Angeles, CA, 50033, USA
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Lebovitz HE, Ludvik B, Kozakowski J, Tarnowski W, Zelewski M, Yaniv I, Schwartz T. Gastric electrical stimulation treatment of type 2 diabetes: effects of implantation versus meal-mediated stimulation. A randomized blinded cross-over trial. Physiol Rep 2015; 3:e12456. [PMID: 26177957 PMCID: PMC4552533 DOI: 10.14814/phy2.12456] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 06/12/2015] [Accepted: 06/15/2015] [Indexed: 01/14/2023] Open
Abstract
Gastric electrical stimulation with the implanted DIAMOND device has been shown to improve glycemic control and decrease weight and systolic blood pressure in patients with type 2 diabetes inadequately controlled with oral antidiabetic agents. The objective of this study was to determine if device implantation alone (placebo effect) contributes to the long-term metabolic benefits of DIAMOND(®) meal-mediated gastric electrical stimulation in patients with type 2 diabetes. The study was a 48 week randomized, blinded, cross-over trial in university centers comparing glycemic improvement of DIAMOND(®) implanted patients with type 2 diabetic with no activation of the electrical stimulation (placebo) versus meal-mediated activation of the electrical signal. The endpoint was improvement in glycemic control (HbA1c) from baseline to 24 and 48 weeks. In period 1 (0-24 weeks), equal improvement in HbA1c occurred independent of whether the meal-mediated electrical stimulation was turned on or left off (HbA1c -0.80% and -0.85% [-8.8 and -9.0 mmol/mol]). The device placebo improvement proved to be transient as it was lost in period 2 (25-48 weeks). With electrical stimulation turned off, HbA1c returned toward baseline values (8.06 compared to 8.32%; 64.2 to 67.4 mmol/mol, P = 0.465). In contrast, turning the electrical stimulation on in period 2 sustained the decrease in HbA1c from baseline (-0.93%, -10.1mmol/mol, P = 0.001) observed in period 1. The results indicate that implantation of the DIAMOND device causes a transient improvement in HbA1c which is not sustained beyond 24 weeks. Meal-mediated electrical stimulation accounts for the significant improvement in HbA1c beyond 24 weeks.
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Affiliation(s)
- Harold E Lebovitz
- State University of New York Health Science Center at Brooklyn, Brooklyn, New York
| | - Bernhard Ludvik
- Internal Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Wieslaw Tarnowski
- Medical Center of Postgraduate Education, Bielanski Hospital, Warsaw, Poland
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Wong SKH, Kong APS, Luk AOY, Ozaki R, Ng VWS, Lebovitz HE, Ng EKW, Chan JCN. A pilot study to compare meal-triggered gastric electrical stimulation and insulin treatment in Chinese obese type 2 diabetes. Diabetes Technol Ther 2015; 17:283-90. [PMID: 25710812 PMCID: PMC4365444 DOI: 10.1089/dia.2014.0234] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastrointestinal electromodulation therapy is a novel alternative for achieving diabetes control without traditional bariatric surgery. We compared the efficacy of a meal-initiated implantable gastric contractility modulation (GCM) device with that of insulin therapy in obese Chinese type 2 diabetes (T2D) patients, for whom oral antidiabetes drugs (OADs) had failed. PATIENTS AND METHODS Sixteen obese (body mass index, 27.5-40.0 kg/m(2)) T2D patients with a glycated hemoglobin (HbA1c) level of >7.5% on maximal doses of two or more OADs were offered either insulin therapy (n=8) or laparoscopic implantation of a GCM (n=8). We compared changes in body weight, waist circumference (WC), and HbA1c level 1 year after surgery. RESULTS The GCM and insulin groups had similar baseline body weight and HbA1c. At 12 months, body weight (-3.2±5.2 kg, P=0.043) and WC (-3.8±4.5 cm, P=0.021) fell in the GCM group but not in the insulin group (P<0.05 for between-group difference). At 6 and 12 months, the HbA1c level fell by 1.6±1.1% and 0.9±1.6% (P=0.011), compared with 0.6±0.3% and 0.6±0.3% (P=0.08) for the insulin group (P=0.15 for between-group difference). The mean 24-h systolic blood pressure (BP) fell by 4.5±1.0 mm Hg in the GCM group (P=0.017) but not in the insulin group. The GCM group required fewer antidiabetes medications (P<0.05) and BP-lowering drugs (P<0.05) than the insulin group. A subgroup analysis showed that patients with a triglyceride level of <1.7 mmol/L had a tendency toward a lower HbA1c level (P=0.090) compared with the controls. CONCLUSIONS In obese T2D patients for whom OADs had failed, GCM implantation was a well-tolerated alternative to insulin therapy, with a low triglyceride level as a possible predictor for glycemic response.
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Affiliation(s)
- Simon Kin-Hung Wong
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Risa Ozaki
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Vanessa Wan-Sze Ng
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Harold E. Lebovitz
- Division of Endocrinology, The State University of New York Health Science Center at Brooklyn, Brooklyn, New York
| | - Enders Kwok-wai Ng
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong Special Administrative Region, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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17
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Gastric electrical stimulation for the treatment of obesity: from entrainment to bezoars-a functional review. ISRN GASTROENTEROLOGY 2013; 2013:434706. [PMID: 23476793 PMCID: PMC3582063 DOI: 10.1155/2013/434706] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Accepted: 01/08/2013] [Indexed: 12/29/2022]
Abstract
GROWING WORLDWIDE OBESITY EPIDEMIC HAS PROMPTED THE DEVELOPMENT OF TWO MAIN TREATMENT STREAMS: (a) conservative approaches and (b) invasive techniques. However, only invasive surgical methods have delivered significant and sustainable benefits. Therefore, contemporary research exploration has focused on the development of minimally invasive gastric manipulation methods featuring a safe but reliable and long-term sustainable weight loss effect similar to the one delivered by bariatric surgeries. This antiobesity approach is based on placing external devices in the stomach ranging from electrodes for gastric electrical stimulation to temporary intraluminal bezoars for gastric volume displacement for a predetermined amount of time. The present paper examines the evolution of these techniques from invasively implantable units to completely noninvasive patient-controllable implements, from a functional, rather than from the traditional, parametric point of view. Comparative discussion over the available pilot and clinical studies related to gastric electrical stimulation outlines the promises and the fallacies of this concept as a reliable alternative anti-obesity strategy.
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18
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Bohdjalian A, Aviv R, Prager G, Schindler K, Bacher E, Langer F, Ludvik B. Gastric stimulation in the digestive period modifies length and contractility of the inter-digestive period in obese non-diabetic and diabetic subjects. Obes Surg 2013; 22:1465-72. [PMID: 22761022 DOI: 10.1007/s11695-012-0703-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND The association between phase II of the motor migratory complex (MMC) and hunger remains poorly understood, which may be important in non-diabetic and diabetic obese subjects where gastric inter-digestive motility has been often reported as impaired. We characterize phase II of the MMC and its predictive power on food intake, weight loss, and glycemia in non-diabetic (OB) and diabetic (DM) obese subjects treated with gastric stimulation for 6 months. METHODS Twelve OB and 12 DM subjects were implanted with bipolar electrodes connected to a gastric stimulator capable of recording antrum electromechanical activity. RESULTS The phase II mean interval size and duration increased from 156 ± 121 to 230 ± 228 s and from 98 ± 33 to 130 ± 35 min (p < 0.05) in OB and from 158 ± 158 to 180 ± 112 s and from 77 ± 26 to 109 ± 18 min (p < 0.05) in DM after 6 months. There was a significant trend of meals to interrupt the late rather than the early phase II. Nonlinear regression analysis demonstrated that weight loss in OB was significantly associated with the change in interval size of the late phase II and with phase II duration. In the DM group, weight loss and glycemia were also significantly associated with the change in the interval size of the early phase II. CONCLUSIONS Gastric stimulation delivered in the digestive period can modify the length of the MMC and the contractility in its longest component, phase II. The duration and contractility of the MMC can determine to some extent future intake and, thus, influence energy balance.
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Affiliation(s)
- A Bohdjalian
- Department of Surgery, University of Vienna (Vienna General Hospital), Waehringerguertel 18-20, 1090, Vienna, Austria.
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Liao D, Lu X, Kirkup AJ, Jiang W, Grundy D, Gregersen H. Interdependency of stress relaxation and afferent nerve discharge in rat small intestine. J Biomech 2012; 45:1574-9. [DOI: 10.1016/j.jbiomech.2012.04.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Revised: 01/27/2012] [Accepted: 04/12/2012] [Indexed: 01/13/2023]
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Mizrahi M, Ben Ya'acov A, Ilan Y. Gastric stimulation for weight loss. World J Gastroenterol 2012; 18:2309-19. [PMID: 22654422 PMCID: PMC3353365 DOI: 10.3748/wjg.v18.i19.2309] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2011] [Revised: 09/02/2011] [Accepted: 04/28/2012] [Indexed: 02/06/2023] Open
Abstract
The prevalence of obesity is growing to epidemic proportions, and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss. Behavior and lifestyle therapy are safe treatments for obesity in the short term, but the durability of the weight loss is limited. Although promising obesity drugs are in development, the currently available drugs lack efficacy or have unacceptable side effects. Surgery leads to long-term weight loss, but it is associated with morbidity and mortality. Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders. GES is a promising, minimally invasive, safe, and effective method for treating obesity. External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time. In addition, data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES. This may involve alteration of secretion of hormones associated with hunger or satiety. Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment’s outcome. Here, we review the current status, potential mechanisms of action, and possible future applications of gastric stimulation for obesity.
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ASICs Do Not Play a Role in Maintaining Hyperalgesia Induced by Repeated Intramuscular Acid Injections. PAIN RESEARCH AND TREATMENT 2011; 2012:817347. [PMID: 22191025 PMCID: PMC3236358 DOI: 10.1155/2012/817347] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2011] [Revised: 08/29/2011] [Accepted: 09/04/2011] [Indexed: 11/30/2022]
Abstract
Repeated intramuscular acid injections produce long-lasting mechanical hyperalgesia that depends on activation of ASICs. The present study investigated if pH-activated currents in sensory neurons innervating muscle were altered in response to repeated acid injections, and if blockade of ASICs reverses existing hyperalgesia. In muscle sensory neurons, the mean acid-evoked current amplitudes and the biophysical properties of the ASIC-like currents were unchanged following acidic saline injections when compared to neutral pH saline injections or uninjected controls. Moreover, increased mechanical sensitivity of the muscle and paw after the second acid injection was unaffected by local blockade of ASICs (A-317567) in the muscle. As a control, electron microscopic analysis showed that the tibial nerve was undamaged after acid injections. Our previous studies demonstrated that ASICs are important in the development of hyperalgesia to repeated acid injections. However, the current data suggest that ASICs are not involved in maintaining hyperalgesia to repeated intramuscular acid injections.
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Lu X, Guo X, Mattar SG, Navia JA, Kassab GS. Distension-induced gastric contraction is attenuated in an experimental model of gastric restraint. Obes Surg 2011; 20:1544-51. [PMID: 20706803 PMCID: PMC2950927 DOI: 10.1007/s11695-010-0240-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Gastric distension has important implications for motility and satiety. The hypothesis of this study was that distension affects the amplitude and duration of gastric contraction and that these parameters are largely mediated by efferent vagus stimulation. METHODS A novel isovolumic myograph was introduced to test these hypotheses. The isovolumic myograph isolates the stomach and records the pressure generated by the gastric contraction under isovolumic conditions. Accordingly, the phasic changes of gastric contractility can be documented. A group of 12 rats were used under in vivo conditions and isolated ex vivo conditions and with two different gastric restraints (small and large) to determine the effect of degree of restraint. RESULTS The comparison of the in vivo and ex vivo contractility provided information on the efferent vagus mediation of gastric contraction, i.e., the in vivo amplitude and duration reached maximum of 12.6 ± 2.7 mmHg and 19.8 ± 5.6 s in contrast to maximum of 5.7 ± 0.9 mmHg and 7.3 ± 1.3 s in ex vivo amplitude and duration, respectively. The comparison of gastric restraint and control groups highlights the role of distension on in vivo gastric contractility. The limitation of gastric distension by restraint drastically reduced the maximal amplitude to below 2.9 ± 0.2 mmHg. CONCLUSIONS The results show that distension-induced gastric contractility is regulated by both central nervous system and local mechanisms with the former being more substantial. Furthermore, the gastric restraint significantly attenuates gastric contractility (decreased amplitude and shortened duration of contraction) which is mediated by the efferent vagus activation. These findings have important implications for gastric motility and physiology and may improve our understanding of satiety.
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Affiliation(s)
- Xiao Lu
- Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA
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Chen JH, Song GQ, Yin J, Sun Y, Chen JDZ. Gastric electrical stimulation reduces visceral sensitivity to gastric distention in healthy canines. Auton Neurosci 2010; 160:16-20. [PMID: 21126929 DOI: 10.1016/j.autneu.2010.10.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2010] [Revised: 10/12/2010] [Accepted: 10/28/2010] [Indexed: 12/27/2022]
Abstract
The aim of this study was to investigate the effects and mechanisms of gastric electrical stimulation (GES) on proximal stomach distention-induced visceral sensitivity. Isobaric gastric distention was performed using a barostat system in 8 normal and 6 vagotomized dogs and animal behaviors were noted and graded. The normal dogs were studied in 4 sessions: control (no GES), short pulse GES, long pulse GES, and dual-pulse GES, and the vagotomized dogs were studied in three sessions: control (no GES), long pulse GES and guanethidine. It was found that: 1) proximal stomach distention-induced behavioral changes were mediated by vagal and sympathetic pathways. The total behavior score (TBS) was 40.6 ± 7.4 in the controls, 15.3 ± 8.9 in vagotomized dogs (P=0.006 vs. control) and 8.8 ± 0.9 in the vagotomized dogs with guanethidine (P=0.04 vs. vagotomy). The behavioral changes were mediated via the vagal pathway at distention pressures below 20 mmHg, but mediated via both the vagal and sympathetic pathways at distention pressures equal to and above 20 mmHg. 2) GES with long pulses or dual pulses but not short pulses reduced the distention-induced behavioral score (P=0.003, P=0.006 and P=0.7, respectively) and the effects of GES of long pulses might be mediated via the vagal and sympathetic pathways. In conclusion, gastric distention-induced visceral sensitivity is mediated via the vagal pathway at low distention pressures but via both vagal and sympathetic pathways at high distention pressures. GES with long but not short pulses reduces distention-induced visceral sensitivity.
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Affiliation(s)
- Ji-Hong Chen
- Division of Gastroenterology, University of Texas Medical Branch, Galveston, United States
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Schwartz A, Ort T, Kajekar R, Wade PR, Hornby PJ. Electrical stimulation of the isolated rat intestine in the presence of nutrient stimulus enhances glucagon-like peptide-1 release. Physiol Meas 2010; 31:1147-59. [PMID: 20664162 DOI: 10.1088/0967-3334/31/9/006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The release of small intestinal hormones by constituents of ingested food, such as fatty acids, is integral to post-prandial responses that reduce food intake. Recent evidence suggests that small intestinal electrical stimulation reduces food intake, although the mechanism of action is debated. To test the hypothesis that intestinal stimulation directly alters hormone release locally we used isolated rat distal ileum and measured glucagon-like peptide-1 (GLP-1) released in the presence or absence of linoleic acid (LA) and electrical field stimulation (EFS). Intact segments were oriented longitudinally between bipolar stimulating electrodes in organ bath chambers containing modified Krebs-Ringers bicarbonate (KRB) buffer including protease inhibitors. Incubation in LA (3 mg ml(-1)) for 45 min increased GLP-1 concentration (21.9 +/- 2.6 pM versus KRB buffer alone 3.6 +/- 0.1 pM). Eleven electrical stimulation conditions were tested. In the presence of LA none of the stimulation conditions inhibited LA-evoked GLP-1 release, whereas two high frequency short pulse widths (14 V, 20 Hz, 5 ms and 14 V, 40 Hz, 5 ms) and one low frequency long pulse width (14 V, 0.4 Hz, 300 ms) EFS conditions enhanced LA-evoked GLP-1 release by >250%. These results are consistent with a local effect of intestinal electrical stimulation to enhance GLP-1 release in response to luminal nutrients in the intestines. Enhancing hormone release could improve the efficacy of intestinal electrical stimulation and provide a potential treatment for obesity and metabolic conditions.
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Affiliation(s)
- Ann Schwartz
- Immunology, Centocor Research & Development, Inc., Radnor, PA 19087, USA
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Li S, Chen JDZ. Cellular effects of gastric electrical stimulation on antral smooth muscle cells in rats. Am J Physiol Regul Integr Comp Physiol 2010; 298:R1580-7. [DOI: 10.1152/ajpregu.00024.2010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The cellular effects of gastric electrical stimulation (GES), which has recently been introduced as a potential therapy for the treatment of gastroparesis and obesity, were investigated in rat antrum smooth muscle cells (SMCs). Effects on cell membrane potentials of single electrical current pulses (pulse width from 0.1 ms to 200 ms) and 2-s pulse train stimuli with different pulse widths (0.1–4 ms), different frequencies (20–200 Hz), and different intensities were studied: 1) the stimulus amplitude had an exponential relationship to the pulse width from 2 ms to 200 ms, along with a rapidly rising strength-duration curve at pulse widths less than 5 ms, and a relatively flat curve at pulse widths greater than 50 ms; 2) when the pulse frequency was at 80 Hz or above, pulse train electrical stimulation, with a pulse width of 2 ms or above but not ≤1 ms, was able to depolarize cell membrane potentials to above −30 mV and/or generate action potentials. Electrical stimulation with a single long pulse and a width of 50 ms or greater is effective in depolarizing cell membrane potentials of SMCs with low amplitude. Pulse train electrical stimulation with a pulse width of ≤1 ms fails to generate action potentials in SMCs, whereas pulse train electrical stimulation with a pulse width of 2–4 ms and a sufficiently high pulse frequency is able to generate action potentials. These cellular findings may be useful in optimizing stimulation parameters of GES.
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Affiliation(s)
- Shiying Li
- Veterans Research and Education Foundation, Veterans Affairs Medical Center, Oklahoma City, Oklahoma; and
| | - Jiande D. Z. Chen
- Veterans Research and Education Foundation, Veterans Affairs Medical Center, Oklahoma City, Oklahoma; and
- Division of Gastroenterology, University of Texas Medical Branch, Galveston, Texas
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Buchwald H, Menchaca HJ, Michalek VN, Suguitani NT, Singh H, George P, Belani KG. Micro-orifice metabolic/bariatric surgery under IV sedation/local anesthesia: porcine feasibility study. Obes Surg 2010; 20:500-5. [PMID: 20127287 DOI: 10.1007/s11695-010-0081-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2009] [Accepted: 01/06/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND As the volume and scope of metabolic/bariatric surgery increases, there is a definite trend toward the development and utilization of simpler and safer procedures. The laparoscopic approach has certain disadvantages that can be avoided by a technique for abdominal access via a micro-orifice incision under intravenous (IV) sedation/local anesthesia, without general anesthesia, insufflation, and intubation. METHODS In a porcine model, we used the implantation of the TANTALUS System as a prototype for the micro-orifice, IV sedation/local anesthesia approach. The study was conducted in five ex vivo stomachs, four cadavers, and six in vivo animals, the last four of which underwent surgery under IV sedation/local anesthesia. RESULTS Accurate implantation of electrodes was achieved in all ex vivo, cadaver, and in vivo preparations with no mucosal penetration, confirmed by examination of the open porcine stomachs. Operative time in this learning setting was 1 h 43 min in the last three operated animals. Feasibility was established for using the single incision to tunnel and construct subcutaneous pockets for the pulse generator and the charge coil. No major operative or postoperative complications occurred. CONCLUSIONS Using the TANTALUS System as a metabolic/bariatric surgery prototype model, this study successfully tested the feasibility of micro-orifice surgery, under IV sedation/local anesthesia. This study will be followed by human trials that may offer an alternative approach for the performance of metabolic/bariatric surgery.
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Affiliation(s)
- Henry Buchwald
- Department of Surgery, University of Minnesota, MMC 290, Minneapolis, MN 55455, USA.
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Bohdjalian A, Prager G, Rosak C, Weiner R, Jung R, Schramm M, Aviv R, Schindler K, Haddad W, Rosenthal N, Ludvik B. Improvement in glycemic control in morbidly obese type 2 diabetic subjects by gastric stimulation. Obes Surg 2009; 19:1221-7. [PMID: 19575272 DOI: 10.1007/s11695-009-9901-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2009] [Accepted: 06/02/2009] [Indexed: 12/28/2022]
Abstract
BACKGROUND Gastric electrical stimulation synchronized to the refractory period of gastric electrical activity and applied during meals was evaluated for safety and for improvement of body weight and glycemic control in obese type 2 diabetes. METHODS The study involved obese diabetic type 2 (ODM) patients in a multicenter open-label European feasibility trial. A total of 24 ODM (nine males, 15 females) treated with insulin and/or oral hyperglycemic agents and body mass index between 33.3 to 49.7 kg/m(2) were implanted laparoscopically with a TANTALUS system. RESULTS There were 18 adverse events related to the implant procedure or the device reported in 12 subjects. All were short lived and resolved with no sequelae. In the 21 subjects that reached the 1-year visit weight was reduced by 4.5 +/- 2.7 kg (p < 0.05) and HbA1c by 0.5 +/- 0.3% (p < 0.05). In a subgroup (n = 11) on stable or reduced oral medication, weight was reduced by 6.3 +/- 3.4 kg (p < 0.05) and HbA1c by 0.9 +/- 0.4% (p < 0.05). The group on insulin (n = 6) had no significant changes in weight and HbA1c. CONCLUSIONS The TANTALUS system is well tolerated in obese type 2 diabetic subjects. Gastric electrical stimulation can potentially improve glucose metabolism and induce weight loss in obese diabetic patients, who are not well controlled on oral antidiabetic therapy. Further evaluation is required to determine whether this effect is due to induced weight loss and/or to direct signal dependent mechanisms.
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Affiliation(s)
- Arthur Bohdjalian
- Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria
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Sanmiguel CP, Conklin JL, Cunneen SA, Barnett P, Phillips EH, Kipnes M, Pilcher J, Soffer EE. Gastric electrical stimulation with the TANTALUS System in obese type 2 diabetes patients: effect on weight and glycemic control. J Diabetes Sci Technol 2009; 3:964-70. [PMID: 20144347 PMCID: PMC2769967 DOI: 10.1177/193229680900300445] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND The TANTALUS System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. METHOD Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 +/- 1 kg/m(2), hemoglobin A1c [HbA1c] 8.5 +/- 0.2%).Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. RESULTS Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 +/- 0.7% to 7.6 +/- 1%, p < .01. Weight was also significantly reduced from 107.7 +/- 21.1 to 102.4 +/- 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss (R(2) = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). CONCLUSIONS Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.
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Affiliation(s)
| | | | | | | | | | - Mark Kipnes
- Diabetes and Glandular Disease Research Associates Inc., San Antonio, Texas
| | - John Pilcher
- New Dimension Weight Loss Surgery, San Antonio, Texas
| | - Edy E. Soffer
- Cedars Sinai Medical Center, Los Angeles, California
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Hasler WL. Methods of gastric electrical stimulation and pacing: a review of their benefits and mechanisms of action in gastroparesis and obesity. Neurogastroenterol Motil 2009; 21:229-43. [PMID: 19254353 DOI: 10.1111/j.1365-2982.2009.01277.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Development of gastric electrical stimulation techniques for treatment of gastric dysmotility syndromes and obesity has been a long-standing goal of investigators and clinicians. Depending on stimulus parameters and sites of stimulation, such methods have a range of theoretical benefits including entrainment of intrinsic gastric electrical activity, eliciting propagating contractions and reducing symptomatology in patients with gastroparesis and reducing appetite and food intake in individuals with morbid obesity. Additionally, gastric stimulation parameters have extragastrointestinal effects including alteration of systemic hormonal and autonomic neural activity and modulation of afferent nerve pathways projecting to the central nervous system that may represent important mechanisms of action. Numerous case series and smaller numbers of controlled trials suggest clinical benefits in these two conditions, however better controlled trials are mandated to confirm their efficacy. Current research is focusing on novel stimulation methods to better control symptoms in gastroparesis and promote weight reduction in morbid obesity.
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Affiliation(s)
- W L Hasler
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, MI 48109, USA.
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Improvement in glycemic control by gastric electrical stimulation (TANTALUS) in overweight subjects with type 2 diabetes. Surg Endosc 2008; 23:1955-60. [PMID: 19067068 DOI: 10.1007/s00464-008-0222-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2008] [Accepted: 10/13/2008] [Indexed: 12/18/2022]
Abstract
BACKGROUND The TANTALUS system (MetaCure Ltd.) is a minimally invasive implantable gastric stimulation modality that does not exhibit malabsorptive or restrictive characteristics. The device applies gastric contractility modulation (GCM) signals to the stomach antrum. The signals are delivered in synchronization to the native electrical activity of the stomach during meals. Retrospective analysis of previous studies indicated that type 2 diabetes mellitus (T2DM) subjects on oral medication with hemoglobin A1c (HbA1c) between 7.5% and 9.5% are the population with most potential benefit from the treatment. The current study includes subjects enrolled prospectively within that range of HbA1c. AIM To prospectively investigate the potential effect of the TANTALUS system on glycemic control and weight in overweight subjects with T2DM. METHODS In this European multicenter, open-label study, 13 T2DM obese (6 male, 7 female, BMI 37.2 +/- 1.0 kg/m(2), range 30.4-44.0 kg/m(2)) subjects treated with oral antidiabetic medications but with poor glycemic control (HbA1c > or = 7%, range 7.3-9.5%) were implanted laparoscopically with the TANTALUS system. RESULTS Thirteen subjects that had completed 3 months of treatment showed a significant reduction in HbA1c from 8.0 +/- 0.2% to 6.9 +/- 0.1% (p < 0.05), whereas fasting blood glucose decreased from 175 +/- 6 mg/dL to 127 +/- 8 mg/dL (p < 0.05). The glycemic improvement was accompanied by reduction in weight from 104.4 +/- 4.4 kg to 99.7 +/- 4.8 kg, and in waist circumference from 122.3 +/- 3.2 cm to 117.0 +/- 3.0 cm. CONCLUSIONS Interim results with the TANTALUS system suggest that this stimulation regime can potentially improve glucose levels and induce moderate weight loss in obese T2DM subjects on oral antidiabetic therapy with poor glycemic control. Further evaluation is required to determine whether this effect is due to induced weight loss and/or due to direct signal-dependent mechanisms.
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31
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Frøkjaer JB, Ejskjaer N, Rask P, Andersen SD, Gregersen H, Drewes AM, Funch-Jensen P. Central neuronal mechanisms of gastric electrical stimulation in diabetic gastroparesis. Scand J Gastroenterol 2008; 43:1066-75. [PMID: 18609155 DOI: 10.1080/00365520802028221] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The mechanisms underlying symptom improvement in gastric electrical stimulation (GES) are not fully understood. Modulation of the central nervous system excitability may be involved. The objective of the study was to investigate the central effects of GES, including the possible modulation of the visceral sensory nervous system. MATERIAL AND METHODS A gastric electrical stimulator was implanted in seven diabetic patients with medically refractory gastroparesis. A double-blinded protocol was used to investigate the patients at baseline and one month after recovery with the stimulator turned on and off (1-month periods). The following assessments were carried out: mechanical, thermal and electrical stimulations with sensory recordings in the esophagus and duodenum, and standardized, self-administered, daily symptom questionnaires. RESULTS No difference was found between baseline and the on- and off periods in overall gut pain thresholds across all stimulus modalities in the esophagus (p=0.63), duodenum (p=0.19) or esophagus and duodenum combined (p=0.76). No difference in the sensory response to mechanical stimulation was found in the esophagus before (all p>0.31) and after (all p>0.43) smooth muscle relaxation with butylscopolamine. Similar findings were observed in the duodenum. No differences were found in thermal sensitivity (esophagus (p=0.67) and duodenum (p=0.17)), sensory response to electrical stimulation (esophagus (p=0.57) and duodenum (p=0.52)) or induced somatic referred pain areas (esophagus (p=0.75) and duodenum (p=0.51)). No difference was seen in the induced somatic referred pain areas or self-reported symptoms. CONCLUSIONS No evidence was found for GES-induced modulation of the visceral sensory system and central excitability. However, GES has been proven to modulate the central nervous system in animal studies, necessitating further human experiments in order unambiguously to establish the possible central effects of GES.
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Affiliation(s)
- Jens B Frøkjaer
- Center for Visceral Biomechanics and Pain, Aalborg Hospital, Aalborg, Denmark
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Policker S, Lu H, Haddad W, Aviv R, Kliger A, Glasberg O, Goode P. Electrical stimulation of the gut for the treatment of type 2 diabetes: the role of automatic eating detection. J Diabetes Sci Technol 2008; 2:906-12. [PMID: 19885277 PMCID: PMC2769790 DOI: 10.1177/193229680800200524] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Automatic eating detection (AED) can potentially support treatments that need to be synchronized with food intake. This article analyzes an implantable AED device working in conjunction with gastric stimulation intended to treat type 2 diabetes (T2DM). The device continuously senses for changes in tissue impedance and electrical activity induced by food intake and initiates treatment sessions upon detection. This article reviews AED performance as well as its relevance to treatment outcomes. METHODS Obese T2DM (n = 12) were implanted with gastric leads and the TANTALUS device. An AED algorithm was embedded in the device and was used to initiate periods of electrical stimulation during food intake. AED performance was assessed using patients' food diaries. The treatment outcome at 37 weeks postimplants was correlated with the rates of stimulation during large meals vs stimulation during periods of no caloric intake. RESULTS The algorithm was able to detect 73% of meals consumed while sensing. The rate of false stimulations was 28%. Stimulation during meals was significantly correlated (R(2) = 0.45, p < 0.05) with hemoglobin A1c change (average drop in hemoglobin A1c was -1 +/- 0.4%) but not with changes in body weight (average drop -4.7 +/- 2.8 kg). Stimulation during periods with no caloric intake was negatively correlated with hemoglobin A1c reduction (R(2) = 0.27, p < 0.05). CONCLUSIONS Sensing of gastric activity can be used for detection of food intake. The synchronization of gastric stimulation to periods of food intake is correlated with metabolic outcomes. AED may also benefit other applications such as drug delivery and control of food restriction devices.
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Affiliation(s)
- Shai Policker
- MetaCure Inc., Orangeburg, New York 10962-2698, USA.
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33
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Sanmiguel CP, Haddad W, Aviv R, Cunneen SA, Phillips EH, Kapella W, Soffer EE. The TANTALUS system for obesity: effect on gastric emptying of solids and ghrelin plasma levels. Obes Surg 2008; 17:1503-9. [PMID: 18219779 DOI: 10.1007/s11695-008-9430-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND Gastric electrical stimulation (GES), using the implantable TANTALUS System, is being explored as a treatment for obesity. The system delivers nonstimulatory electrical signals synchronized with gastric slow waves, resulting in stronger contractions. We hypothesized that this GES may enhance gastric emptying and as a result affect plasma ghrelin and insulin homeostasis. The aim was to test the effect of GES on gastric emptying of solids and on ghrelin and insulin blood levels in obese subjects. METHODS The system consists of 3 pairs of gastric electrodes connected to an implantable pulse generator. Gastric emptying test (GE) of solids was performed twice, on separate days, a few weeks after implantation, before and after initiation of stimulation. Blood samples for ghrelin and insulin were taken at baseline and at 15, 30, 60 and 120 min after the test meal. RESULTS There were 11 females, 1 male, mean age 39.1 +/- 8.9 years, mean BMI 41.6 +/- 3.4. Data is available from 11 subjects; GE was normal in 9 subjects and accelerated in 2 subjects. GES significantly accelerated GE compared to control: percent retention at 2 hours 18.7 +/- 12.2 vs 31.9 +/- 16.4, respectively (P < 0.01). Overall, there was no significant change in ghrelin or insulin profile after food intake. Ghrelin levels fell significantly at 60 min compared to baseline during stimulation (P = 0.014) and control (P = 0.046). CONCLUSION GES results in a significant acceleration of gastric emptying of solids in obese subjects. GES did not have a significant effect on postprandial ghrelin levels when compared to control.
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Affiliation(s)
- Claudia P Sanmiguel
- GI Motility Program, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
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Sanmiguel CP, Aviv R, Policker S, Haddad W, Brody F, Soffer EE. Association between gastric electromechanical activity and satiation in dogs. Obesity (Silver Spring) 2007; 15:2958-63. [PMID: 18198304 DOI: 10.1038/oby.2007.353] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE The objective of this study was to validate the use of impedance for measurement of antral contractions and to determine the relationship between food-induced changes in gastric motility and satiation. RESEARCH METHODS AND PROCEDURES In Experiment 1, three dogs were implanted with an antral strain gauge and bipolar electrodes for measurement of local tissue impedance. Impedance and strain gauge recordings were obtained simultaneously during antral contractions to correlate impedance changes with contractile events. In Experiment 2, seven dogs were implanted with two pairs of gastric electrodes for simultaneous recording of slow wave activity and impedance. The changes in the rate of slow waves and of antral contractions assessed by impedance during food intake were characterized. RESULTS Variations in strain gauge amplitude were highly correlated with changes in antral impedance (R2: 0.70 to 0.82, p < 0.05). In Experiment 2, slow wave rate was significantly reduced after food intake and reached a nadir at satiation (5.0 +/- 0.3 vs. 3.8 +/- 0.5 events/min, p < 0.001). Likewise, the amplitude of antral contractions assessed by variations in impedance was significantly increased after food intake, peaking at satiation (5.3 +/- 1.4 vs. 12.2 +/- 4.3 Ohms, p < 0.01). DISCUSSION Measurement of impedance is a reliable tool for assessing gastric contractility. Food ingestion significantly reduces slow wave rate and enhances antral contractions. Peak changes in these two variables occur at the time of satiation. Electrical measurements of both slow waves and impedance may be used to estimate gastric motility and satiation.
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Affiliation(s)
- Claudia P Sanmiguel
- Department of Gastroenterology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
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35
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Characterization of T9-T10 spinal neurons with duodenal input and modulation by gastric electrical stimulation in rats. Brain Res 2007; 1152:75-86. [PMID: 17433808 DOI: 10.1016/j.brainres.2007.03.034] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2007] [Revised: 03/12/2007] [Accepted: 03/12/2007] [Indexed: 10/23/2022]
Abstract
Gastric electrical stimulation (GES) has been suggested as a therapy for patients with gastric motility disorders or morbid obesity. However, it is unclear whether GES also affects intestinal sensory and motor functions. Furthermore, little is known about intraspinal visceroreceptive transmission and processing for duodenal afferent information. The aims of this study were to characterize responses of thoracic spinal neurons to duodenal distension, to determine the afferent pathway and to examine the effects of GES on activity of these neurons. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Graded duodenal distension (DD, 0.2-0.6 ml, 20 s) was produced by water inflation of a latex balloon surgically placed into the duodenum. One pair of platinum electrodes (1.0-1.5 cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for one minute: GES-A (6 mA, 0.3 ms, 40 Hz, 2 s on, 3 s off), GES-B (6 mA, 0.3 ms, 14 Hz, 0.1 s on, 5 s off), GES-C (6 mA, 3 ms, 40 Hz, 2 s on, 3 s off) and GES-D (6 mA, 200 ms, 12 pulses/min). Results showed that 33/117 (28%) spinal neurons responded to noxious DD (0.4 ml, 20 s). Of these, 7 (6%) neurons had low-threshold responses to DD (<or=0.2 ml) and 26 (22%) had high-threshold responses to DD (>or=0.4 ml). DD-responsive spinal neurons were encountered more frequently in deeper (depth: 0.3-1.2 mm) than in superficial laminae (depth: <0.3 mm) of the dorsal horn (24/67 vs. 9/50, P<0.05). DD excited all 9 superficial neurons. In contrast, 20 deeper neurons were excited and 4 neurons were inhibited by DD. Activity of DD-responsive neurons was affected more frequently with GES-C (13/15, 87%) than GES-A (6/16, 38%), -B (3/15, 20%) and -D (5/14, 36%) (P<0.01). Bilateral cervical vagotomy did not significantly alter the effects of DD and GES on 5/5 neurons. Resiniferatoxin (2.0 microg/kg, i.v.), an ultrapotent agonist of transient receptor potential vanilloid receptor-1 (TRPV1), abolished DD responses and GES effects on all neurons examined in vagotomized rats. Additionally, 29/33 (88%) DD-responsive neurons received inputs from somatic receptive fields on the back, flank and medial/lateral abdominal areas. It was concluded that GES mainly exerted an excitatory effect on T9-T10 spinal neurons with duodenal input transmitted by sympathetic afferent fibers expressing TRPV1; spinal neuronal responses to GES were strengthened with an increased pulse width and/or frequency of stimulation; T9-T10 spinal neurons processed input from the duodenum and might mediate effects of GES on duodenal sensation and motility.
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Abstract
The prevalence of obesity is growing, is driving an increase in the prevalence of diabetes, and is creating a major public health crisis in the United States. Lifestyle and behavior therapy rarely give durable weight loss. There are few medications approved for the treatment of obesity. Those that exist are limited in efficacy and using them in combination does not result in greater weight loss. Surgical treatments for obesity are effective and give durable weight loss, but are accompanied by measurable morbidity and mortality. Several pacing approaches are being tried and are an outgrowth of pacing for gastroparesis. The Transcend(R) pacemaker blocks vagal efferents and delays gastric emptying, giving a 40% loss of excess body weight, if certain screening procedures are employed. The Tantulus pacemaker is still in development but increases antral muscular contractions and delays gastric emptying by stimulation during the absolute refractory period. Weight loss has been 30% of excess body weight, and glycohemoglobin decreased 1.6% in a trial of obese type 2 diabetes. Stimulation to the subdiaphragmatic sympathetics, vagal nerve stimulation with or without unilateral vagotomy, and intestinal pacing are other approaches that are still being evaluated preclinically. Clearly a safe, effective, and durable treatment for obesity is desperately needed. Electrical pacing of the gastrointestinal tract is promising therapeutically, and because pacemakers work through different mechanisms, combining pacemaker treatments may be possible. Rapid progress is being made in the field of electrical stimulation as a treatment for obesity and even greater progress can be expected in the foreseeable future.
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Affiliation(s)
- Frank Greenway
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
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37
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Qin C, Chen JDZ, Zhang J, Foreman RD. Modulatory effects and afferent pathways of gastric electrical stimulation on rat thoracic spinal neurons receiving input from the stomach. Neurosci Res 2006; 57:29-39. [PMID: 17046091 PMCID: PMC1855190 DOI: 10.1016/j.neures.2006.09.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2006] [Revised: 08/29/2006] [Accepted: 09/07/2006] [Indexed: 01/17/2023]
Abstract
Gastric electrical stimulation (GES) has been suggested as a potential therapy for patients with obesity or gastric motility disorders. The aim of this study was to investigate the spinal mechanism of GES effects on gastric functions. Extracellular potentials of single spinal (T9-T10) neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Gastric distension (GD) was produced by air inflation of a balloon. One pair of platinum electrodes (1.0-1.5cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for 1min: GES-A (6mA, 0.3ms, 40Hz, 2s on, 3s off), GES-B (6mA, 0.3ms, 14Hz, 0.1s on, 5s off), GES-C (6mA, 3ms, 40Hz, 2s on, 3s off), GES-D (6mA, 200ms, 12pulses/min). 62/158 (39%) spinal neurons responded to GD (20, 40, 60mmHg, 20s. Most GD-responsive neurons (n=43) had excitatory responses; the remainder had inhibitory (n=12) or biphasic responses (n=7). GES-A, -B, -C and -D affected activity of 12/33 (36%), 4/31 (13%), 22/29 (76%) and 13/30 (43%) GD-responsive neurons, respectively. Bilateral cervical vagotomy did not significantly alter mean excitatory neuronal responses to GD (n=5) or GES (n=6). Resiniferatoxin (2.0microg/kg, i.v.), an ultrapotent agonist of vanilloid receptor-1, abolished excitatory responses to GD and GES in 4/4 neurons recorded in vagotomized rats. The results suggested that GES mainly had an excitatory effect on T9-T10 spinal neurons with gastric inputs; neuronal responses to GES were strengthened with stimulation at an increased pulse width and/or number of pulses. The modulatory effect of GES involved thoracic spinal (sympathetic) afferent fibers containing vanilloid receptor-1.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
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38
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Abstract
BACKGROUND Over the past 20 years, gastric electrical stimulation has received increasing attention among researchers and clinicians. AIM To give a systematic review on the effects, mechanisms and applications of gastric electrical stimulation. METHODS Medline was used to identify the articles to be included in this review. Key words used for the search included gastric electrical stimulation, gastric pacing, electrical stimulation, stomach, gastrointestinal motility, central nervous system, gastroparesis, nausea and vomiting; obesity and weight loss. Combinational uses of these keywords were made to identify relevant articles. Most of the articles included in this review ranged from 1985 to 2006. RESULTS Based on the general search, the review was structured as follows: (i) peripheral and central effects and mechanisms of gastric electrical stimulation; (ii) clinical applications of gastric electrical stimulation for gastroparesis and obesity and (iii) future development of gastric electrical stimulation. CONCLUSIONS Great progress has been made during the past decades. Gastric electrical stimulation has been shown to be effective in normalizing gastric dysrhythmia, accelerating gastric emptying and improving nausea and vomiting. Implantable device has been made available for treating gastroparesis as well as obesity. However, development of a new device and controlled clinical studies are required to further prove clinical efficacy of gastric electrical stimulation.
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Affiliation(s)
- J Zhang
- Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA
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Qin C, Sun Y, Chen JDZ, Foreman RD. Gastric electrical stimulation modulates neuronal activity in nucleus tractus solitarii in rats. Auton Neurosci 2005; 119:1-8. [PMID: 15893702 DOI: 10.1016/j.autneu.2005.01.007] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2004] [Revised: 01/18/2005] [Accepted: 01/31/2005] [Indexed: 11/18/2022]
Abstract
Implantable gastric electric stimulation (GES) has been under investigation for the treatment of gastric motor disorders and obesity. However, possible central mechanisms involving the effects of GES on gastric function are unclear. The purpose of this study was to examine the effects of GES with different parameters on neuronal activity in the nucleus tractus solitarii (NTS) of the medulla. Extracellular potentials of single neurons in NTS were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats. GES with four sets of parameters was applied for one minute: GES-A (6 mA, 0.3 ms, 40 Hz, 2 s-on and 3 s-off), GES-B (20 mA, 0.3 ms, 40 Hz, 2 s-on and 3 s-off), GES-C (6 mA, 6 ms, 40 Hz, 2 s-on and 3 s-off), and GES-D (6 mA, 200 ms, 12 imps/min). 35/118 (30%) neurons in NTS were responsive to gastric distension (GD, 20 mmHg, 20 s). Forty-one percent, 67%, 76% and 42% of all the responsive NTS neurons were affected by GES-A, -B, -C and -D, respectively. More NTS neurons with gastric inputs were affected with GES-C (19/25) than with GES-A (11/27, P<0.05) and GES-D (10/24, P<0.05). Maximal excitatory responses (17.9+/-2.6 imp/s) of NTS neurons to GES-C were significantly greater than GES-D (9.7+/-4.8 imp/s, P<0.05), whereas average duration of excitatory response (74.8+/-4.3 s) of NTS neurons to GES-B was significant longer than GES-A (60.3+/-3.3 s). Gastric electrical stimulation primarily has an excitatory effect on NTS neurons receiving input from the stomach; the central neuronal response to GES is enhanced with stimulation using an increased pulse width and/or amplitude. This modulatory effect of GES on the central neurons receiving vagal inputs may contribute to the neural mechanisms of GES therapy for the treatment of patients with obesity and gastric motility disorders.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190, United States.
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40
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Sengupta JN, Petersen J, Peles S, Shaker R. Response properties of antral mechanosensitive afferent fibers and effects of ionotropic glutamate receptor antagonists. Neuroscience 2004; 125:711-23. [PMID: 15099685 DOI: 10.1016/j.neuroscience.2004.02.018] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2004] [Indexed: 11/19/2022]
Abstract
The ionotropic glutamate receptors N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are present peripherally in the primary sensory afferent neurons innervating the viscera. Multiple studies have reported roles of glutamate receptors in gastric functions. However, no study has previously shown the direct influence of ionotropic glutamate receptor antagonist on vagal sensory neurons. The objective of this study was to investigate the effects of NMDA and AMPA receptor antagonists on mechanotransduction properties of vagal afferent fibers innervating the rat stomach. Action potentials were recorded from the hyponodal vagus nerve innervating the antrum of the Long-Evans rats. For antral distension (AD), a small latex balloon was inserted into the stomach and positioned in the antrum. The antral contractions were recorded with solid-state probe inserted into the water-filled balloon. Antral units were identified to isovolumic (0.2-1 ml) or isobaric AD (5-60 mm Hg). NMDA and AMPA receptor antagonists were injected in a cumulative fashion (1-100 micromol/kg, i.v.). After the conclusion of experiment, the abdomen was opened and receptive field was mapped by probing the serosa of the stomach. Thirty-two fibers were identified to AD. The receptive fields of 26 fibers were located in the posterior part of the antrum. All fibers exhibited spontaneous firing (mean: 7.00+/-0.97 impulses/s). Twenty fibers exhibited a rhythmic firing that was in phase with antral contractions, whereas 12 fibers exhibited non-rhythmic spontaneous firing unrelated to spontaneous antral contraction. Both groups of fibers exhibited a linear increase in responses to graded isovolumic or isobaric distensions. NMDA (memantine HCl and dizocilpine (MK-801)) and AMPA/kainate (6-cyano-7-nitroquinoxaline 2,3-dione; CNQX) receptor antagonists dose-dependently attenuated the mechanotransduction properties of these fibers to AD. However, competitive NMDA antagonist dl-2-amino-5 phosphopentanoic acid (AP-5) had no effect. The study documents that glutamate receptor antagonists can attenuate responses of gastric vagal sensory afferent fibers innervating the distal stomach, offering insight to potential pharmacological agents in the treatment of gastric disorders.
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MESH Headings
- Action Potentials/drug effects
- Action Potentials/physiology
- Animals
- Dilatation/instrumentation
- Dilatation/methods
- Dose-Response Relationship, Drug
- Excitatory Amino Acid Antagonists/pharmacology
- Glutamic Acid/metabolism
- Male
- Mechanoreceptors/drug effects
- Mechanoreceptors/metabolism
- Mechanotransduction, Cellular/drug effects
- Mechanotransduction, Cellular/physiology
- Muscle Contraction/drug effects
- Muscle Contraction/physiology
- Muscle, Smooth/drug effects
- Muscle, Smooth/physiology
- Neurons, Afferent/drug effects
- Neurons, Afferent/metabolism
- Physical Stimulation/instrumentation
- Physical Stimulation/methods
- Pyloric Antrum/drug effects
- Pyloric Antrum/innervation
- Pyloric Antrum/physiology
- Rats
- Rats, Long-Evans
- Receptors, AMPA/antagonists & inhibitors
- Receptors, AMPA/metabolism
- Receptors, Glutamate/drug effects
- Receptors, Glutamate/metabolism
- Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
- Receptors, N-Methyl-D-Aspartate/metabolism
- Vagus Nerve/drug effects
- Vagus Nerve/physiology
- Visceral Afferents/drug effects
- Visceral Afferents/metabolism
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Affiliation(s)
- J N Sengupta
- Division of Gastroenterology and Hepatology, MaccFund Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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