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Bárdos G. Irritable bowel syndrome (IBS): could we decide what is behind? Biol Futur 2024; 75:61-71. [PMID: 38386191 DOI: 10.1007/s42977-024-00205-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 01/18/2024] [Indexed: 02/23/2024]
Abstract
Functional visceral problems are frequently present nowadays in the medical practice probably due to the significant mental and emotional load on people. Although physicians and psychophysiologists are active on the field, still we are far from a complete knowledge, despite the fact that scientists like the Hungarian Professor György Ádám already had initiated a new approach called visceral psychophysiology already a long time ago. In this article, we commemorate Professor Ádám by analyzing one of the most frequent functional disorders, irritable bowel syndrome (IBS), calling psychophysiology for help. First, we try to give a definition, then show the general descriptions and characteristics of IBS. Factors like stress, gender, and gastrointestinal pain are followed by the potential role of the immune system and the neuronal factors as well as the supposed brain mechanisms. We hope that this overview of the IBS-history would show how significant scientists can be decisive in certain fields of the science and practice.
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Affiliation(s)
- György Bárdos
- Institute of Health Promotion and Sport Sciences, Faculty of Education and Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.
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2
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Wiklendt L, Mohd Rosli R, Kumar R, Paskaranandavadivel N, Bampton PA, Maslen L, Costa M, Brookes SJ, O'Grady G, Dinning PG. Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2023; 325:G62-G79. [PMID: 37162180 DOI: 10.1152/ajpgi.00114.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/08/2023] [Accepted: 05/08/2023] [Indexed: 05/11/2023]
Abstract
Patients with irritable bowel syndrome (IBS) have recurrent lower abdominal pain, associated with altered bowel habit (diarrhea and/or constipation). As bowel habit is altered, abnormalities in colonic motility are likely to contribute; however, characterization of colonic motor patterns in patients with IBS remains poor. Utilizing fiber-optic manometry, we aimed to characterize distal colonic postprandial colon motility in diarrhea-predominant IBS. After an overnight fast, a 72-sensor (spaced at 1-cm intervals) manometry catheter was colonoscopically placed to the proximal colon, in 13 patients with IBS-D and 12 healthy adults. Recordings were taken for 2 h pre and post a 700 kcal meal. Data were analyzed with our two developed automated techniques. In both healthy adults and patients with IBS-D, the dominant frequencies of pressure waves throughout the colon are between 2 and 4 cycles per minute (cpm) and the power of these frequencies increased significantly after a meal. Although these pressure waves formed propagating contractions in both groups, the postprandial propagating contraction increase was significantly smaller in patients compared with healthy adults. In healthy adults during the meal period, retrograde propagation between 2 and 8 cpm was significantly greater than antegrade propagation at the same frequencies. This difference was not observed in IBS-D. Patients with IBS-D show reduced prevalence of the retrograde cyclic motor pattern postprandially compared with the marked prevalence in healthy adults. We hypothesize that this reduction may allow premature rectal filling, leading to postprandial urgency and diarrhea.NEW & NOTEWORTHY Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.
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Affiliation(s)
- Lukasz Wiklendt
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Reizal Mohd Rosli
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Raghu Kumar
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | | | - Peter A Bampton
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Lyn Maslen
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Simon J Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Greg O'Grady
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
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Balsiger LM, Carbone F, Raymenants K, Scarpellini E, Tack J. Understanding and managing patients with overlapping disorders of gut-brain interaction. Lancet Gastroenterol Hepatol 2023; 8:383-390. [PMID: 36702144 PMCID: PMC7615746 DOI: 10.1016/s2468-1253(22)00435-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 12/07/2022] [Accepted: 12/10/2022] [Indexed: 01/25/2023]
Abstract
Disorders of gut-brain interaction (DGBI) are frequently encountered in clinical practice, and recommendations for diagnosis and management are well established. In a large subset of patients, more than one DGBI diagnosis is present. This group of patients with more than one DGBI diagnosis have higher symptom severity and impact than patients with only one DGBI diagnosis, and the management approach is not well established for those with overlapping diagnoses. This Review aims to guide clinicians to understand, recognise, and manage overlapping DGBI by identifying causes and pitfalls of overlap conditions, and presenting potential practical approaches to diagnosis, treatment, and follow-up. Several clinical factors can contribute to finding overlapping DGBI, including the anatomical basis of the Rome diagnostic criteria, the potential confusion of symptom descriptors, and patients' biases towards higher symptom intensity ratings. Overlapping DGBI could also be caused by mechanistic factors such as pathophysiological mechanisms involving multiple gastrointestinal segments, and the effect of disorders in one segment on sensorimotor function in remote gastrointestinal parts, through neural or hormonal signalling. Key initial steps in the management of overlapping DGBI are detailed history taking, which can be facilitated using pictograms; carefully assessing the relative timing and cohesion of different symptoms; and recognising associated psychosocial dysfunction. Unnecessary technical investigations and complex combination treatment schedules should be avoided. Based on the identification of the dominant symptom pattern and putative underlying pathophysiological mechanisms, a single treatment modality should preferably be initiated, considering the efficacy spectrum of different therapies. Follow-up of the patient's condition allows the therapeutic approach to be adjusted as needed, while avoiding unnecessary additional technical investigations.
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Affiliation(s)
- Lukas Michaja Balsiger
- Translational Research Center for Gastrointestinal Diseases, Department of Chronic Diseases and Metabolism
| | | | - Karlien Raymenants
- Translational Research Center for Gastrointestinal Diseases, Department of Chronic Diseases and Metabolism
| | | | - Jan Tack
- Translational Research Center for Gastrointestinal Diseases, Department of Chronic Diseases and Metabolism; Department of Gastroenterology, Leuven University Hospitals Belgium; Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Rome Foundation, Raleigh, NC, USA.
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Di Nardo G, Cremon C, Staiano A, Stanghellini V, Borrelli O, Strisciuglio C, Romano C, Mallardo S, Scarpato E, Marasco G, Salvatore S, Zenzeri L, Felici E, Pensabene L, Sestito S, Francavilla R, Quitadamo P, Baldassarre M, Giorgio V, Tambucci R, Ziparo C, Parisi P, Barbaro MR, Barbara G. Role of inflammation in pediatric irritable bowel syndrome. Neurogastroenterol Motil 2023; 35:e14365. [PMID: 35340083 DOI: 10.1111/nmo.14365] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 02/09/2022] [Accepted: 03/15/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND IBS affects a large number of children throughout the world and is thought to be the result of disturbed neuroimmune function along with the brain-gut axis. Although the underlying pathophysiologic mechanisms are not clear, the role of low-grade inflammation and mucosal immune activation in IBS symptom generation has become evident also in subsets of pediatric patients. Animal models provided meaningful insight in the causal relationship between abnormal mucosal immune activation and changes in gastrointestinal (GI) sensory-motor function. Likewise, the development of long-standing GI symptoms fulfilling the current criteria for functional GI disorders after infection gastroenteritis and in patients with IBD or celiac disease in remission further supports this hypothesis. Immune activation, its impact on gut sensory-motor function, and potential implications for symptom generation emerged in both children and adults with IBS. PURPOSE The aim of this review is to summarize the main evidence on the presence of low-grade inflammation and immune activation in children with IBS, its possible role in symptom generation, and its potential implication for new therapeutic strategies.
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Affiliation(s)
- Giovanni Di Nardo
- NESMOS Department, Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Cesare Cremon
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Annamaria Staiano
- Department of Translational Medical Science, "Federico II", University of Naples, Naples, Italy
| | | | - Osvaldo Borrelli
- Division of Neurogastroenterology and Motility, Department of Paediatric Gastroenterology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Claudio Romano
- Pediatric Gastroenterology Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Saverio Mallardo
- Pediatric Department, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Elena Scarpato
- Department of Translational Medical Science, "Federico II", University of Naples, Naples, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Silvia Salvatore
- Pediatric Department, Ospedale "F. Del Ponte", University of Insubria, Varese, Italy
| | - Letizia Zenzeri
- NESMOS Department, Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
- Pediatric Emergency Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Enrico Felici
- Pediatric and Pediatric Emergency Unit, "Umberto Bosio" Center for Digestive Diseases, The Children Hospital, AO SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | - Licia Pensabene
- Department of Medical and Surgical Sciences, Pediatric Unit, University "Magna Graecia" of Catanzaro, Catanzaro, Italy
| | - Simona Sestito
- Department of Medical and Surgical Sciences, Pediatric Unit, University "Magna Graecia" of Catanzaro, Catanzaro, Italy
| | - Ruggiero Francavilla
- Pediatric Section, Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Paolo Quitadamo
- Department of Pediatrics, A.O.R.N. Santobono-Pausilipon, Naples, Italy
| | - Mariella Baldassarre
- Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | | | - Renato Tambucci
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Chiara Ziparo
- NESMOS Department, Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Pasquale Parisi
- NESMOS Department, Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | | | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Schröder L, Regnath F, Glasauer S, Hackenberg A, Hente J, Weilenmann S, Pohl D, von Känel R, Lehnen N. Altered sensorimotor processing in irritable bowel syndrome: Evidence for a transdiagnostic pathomechanism in functional somatic disorders. Front Neurosci 2022; 16:1029126. [PMID: 36440279 PMCID: PMC9682240 DOI: 10.3389/fnins.2022.1029126] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/10/2022] [Indexed: 02/07/2024] Open
Abstract
Objective A recent hypothesis suggests that functional somatic symptoms are due to altered information processing in the brain, with rigid expectations biasing sensorimotor signal processing. First experimental results confirmed such altered processing within the affected symptom modality, e.g., deficient eye-head coordination in patients with functional dizziness. Studies in patients with functional somatic symptoms looking at general, trans-symptomatic processing deficits are sparse. Here, we investigate sensorimotor processing during eye-head gaze shifts in irritable bowel syndrome (IBS) to test whether processing deficits exist across symptom modalities. Methods Study participants were seven patients suffering from IBS and seven age- and gender-matched healthy controls who performed large gaze shifts toward visual targets. Participants performed combined eye-head gaze shifts in the natural condition and with experimentally increased head moment of inertia. Head oscillations as a marker for sensorimotor processing deficits were assessed. Bayes statistics was used to assess evidence for the presence or absence of processing differences between IBS patients and healthy controls. Results With the head moment of inertia increased, IBS patients displayed more pronounced head oscillations than healthy controls (Bayes Factor 10 = 56.4, corresponding to strong evidence). Conclusion Patients with IBS show sensorimotor processing deficits, reflected by increased head oscillations during large gaze shifts to visual targets. In particular, patients with IBS have difficulties to adapt to the context of altered head moment of inertia. Our results suggest general transdiagnostic processing deficits in functional somatic disorders.
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Affiliation(s)
- Lena Schröder
- Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany
- Computational Neuroscience, Institute of Medical Technology, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
- Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität München, Planegg, Germany
| | - Franziska Regnath
- Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany
- Department of Sport and Health Sciences, TUM Graduate School, Technical University of Munich, Munich, Germany
| | - Stefan Glasauer
- Computational Neuroscience, Institute of Medical Technology, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
- Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| | - Anna Hackenberg
- Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany
| | - Juliane Hente
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Sonja Weilenmann
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Daniel Pohl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nadine Lehnen
- Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany
- Insititute of Medical Technology, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
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Josefsson A, Törnblom H, Simrén M. Type of Rectal Barostat Protocol Affects Classification of Hypersensitivity and Prediction of Symptom Severity in Irritable Bowel Syndrome. J Neurogastroenterol Motil 2022; 28:630-641. [PMID: 36250370 PMCID: PMC9577574 DOI: 10.5056/jnm21214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 02/15/2022] [Accepted: 03/03/2022] [Indexed: 11/20/2022] Open
Abstract
Background/Aims Visceral hypersensitivity is an important pathophysiologic mechanism in irritable bowel syndrome (IBS). We compared 2 barostat distension protocols and their ability to distinguish between IBS patients and healthy controls, identify subjects with rectal hypersensitivity, and their associations with gastrointestinal symptom severity. Methods We retrospectively reviewed all patients at our unit that had undergone barostat investigations 2002-2014. Protocol 1 (n = 369) used phasic isobaric distensions with stepwise increments in pressure and protocol 2 (n = 153) used pressure controlled ramp inflations. Both protocols terminated when subjects reported pain or maximum pressure was reached. Thresholds for first sensation, urgency, discomfort and pain were established. Age- and gender-matched controls were used for comparison. The gastrointestinal symptom rating scale-IBS, and the hospital anxiety and depression scale were used for symptom reports. Results A significantly higher proportion of patients was classified as having hypersensitivity in protocol 1 vs protocol 2 for all thresholds (P < 0.001). Patients with visceral hypersensitivity, defined based on rectal pain thresholds in protocol 1 had more severe gastrointestinal symptoms overall as well as anxiety, whereas these associations were weaker or in most cases absent when visceral hypersensitivity was defined based on rectal pain thresholds in protocol 2. Conclusion Our study indicates that a rectal barostat protocol using phasic isobaric distensions with stepwise pressure increments is more sensitive in IBS patients with respect to identifying subjects with rectal hypersensitivity and a link with IBS symptoms.
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Affiliation(s)
- Axel Josefsson
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
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Tu FF, Hellman KM, Roth GE, Dillane KE, Walker LS. Noninvasive bladder testing of adolescent females to assess visceral hypersensitivity. Pain 2022; 163:100-109. [PMID: 34086630 PMCID: PMC8505577 DOI: 10.1097/j.pain.0000000000002311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 04/08/2021] [Indexed: 01/03/2023]
Abstract
ABSTRACT Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that could be performed readily on youth in early risk windows. Therefore, we evaluated the validity and reliability of a noninvasive bladder pain test in 124 healthy premenarchal females (median age 11, [interquartile range 11-12]), as previously studied in adult women. We explored whether psychosocial, sensory factors, and quantitative sensory test results were associated with provoked bladder pain and assessed the relation of bladder pain with abdominal pain history. Compared with findings in young adult females (age 21 [20-28]), results were similar except that adolescents had more pain at first sensation to void (P = 0.005) and lower maximum tolerance volume (P < 0.001). Anxiety, depression, somatic symptoms, and pain catastrophizing predicted provoked bladder pain (P's < 0.05). Bladder pain inversely correlated with pressure pain thresholds (r = -0.25, P < 0.05), but not with cold pressor pain or conditioned pain modulation effectiveness. Bladder pain was also associated with frequency of abdominal pain symptoms (r = 0.25, P = 0.039). We found strong retest reliability for bladder pain at standard levels of sensory urgency in 21 adolescents who attended repeat visits at 6 to 12 months (intraclass correlations = 0.88-0.90). Noninvasive bladder pain testing seems reproducible in adolescent females and may predict abdominal pain symptomatology. Confirmation of our findings and further investigation of the bladder test across menarche will help establish how visceral sensitivity contributes to the early trajectory of pelvic pain risk.
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Affiliation(s)
- Frank F Tu
- Department of Ob/Gyn, NorthShore University HealthSystem Evanston, IL, United States
- Department of Ob/Gyn, University of Chicago, Pritzker School of Medicine, Chicago, IL, United States
| | - Kevin M Hellman
- Department of Ob/Gyn, NorthShore University HealthSystem Evanston, IL, United States
- Department of Ob/Gyn, University of Chicago, Pritzker School of Medicine, Chicago, IL, United States
| | - Genevieve E Roth
- Department of Ob/Gyn, NorthShore University HealthSystem Evanston, IL, United States
- Department of Psychology, Loyola University of Chicago, Chicago, IL, United States
| | - Katlyn E Dillane
- Department of Ob/Gyn, NorthShore University HealthSystem Evanston, IL, United States
| | - Lynn S Walker
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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Mavroudis G, Strid H, Jonefjäll B, Simrén M. Visceral hypersensitivity is together with psychological distress and female gender associated with severity of IBS-like symptoms in quiescent ulcerative colitis. Neurogastroenterol Motil 2021; 33:e13998. [PMID: 33034406 DOI: 10.1111/nmo.13998] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 09/01/2020] [Accepted: 09/07/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND A subset of ulcerative colitis (UC) patients in remission demonstrate IBS-like symptoms. Visceral hypersensitivity is a key pathophysiological mechanism in IBS, but its relevance to IBS-like symptoms in inactive UC remains unclear. METHODS UC patients in remission (UCR) were screened for IBS-like symptoms. Rectal sensitivity was assessed with rectal balloon distensions, with determination of sensory thresholds and unpleasantness/pain intensity ratings. Patients completed questionnaires evaluating gastrointestinal (GI) and psychological symptoms. Age- and gender-matched IBS subjects and healthy controls (HC) also underwent a rectal sensitivity test. KEY RESULTS We included 36 UCR patients (18 with IBS-like symptoms (UCR + IBS) and 18 without (UCR - IBS)), 36 IBS subjects, and 14 HC. UCR and IBS patients were more sensitive to rectal balloon distensions than HC, but no differences between UCR and IBS patients were observed. UCR + IBS patients had lower sensory thresholds and higher unpleasantness ratings than UCR - IBS. In UCR patients, the overall GI symptom severity, pain, and bloating, but not diarrhea, constipation or satiety, were associated with rectal sensitivity. In multivariate analyses, rectal sensitivity, psychological distress, and female gender were identified as factors independently associated with GI symptom severity. 61% of UCR patients demonstrated rectal hypersensitivity, and these patients more commonly reported at least mild bloating and pain, and overall GI symptoms, compared to those with normal rectal sensitivity. CONCLUSION & INFERENCES Visceral hypersensitivity was associated with IBS-like symptoms, in particular pain and bloating, in inactive UC. Together with psychological factors and female gender, visceral hypersensitivity seems to be involved in GI symptom generation in quiescent UC.
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Affiliation(s)
- Georgios Mavroudis
- Department of Internal Medicine, Kungälv Hospital, Kungälv, Sweden.,Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hans Strid
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden
| | - Börje Jonefjäll
- Department of Internal Medicine, Kungälv Hospital, Kungälv, Sweden.,Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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10
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Rustamov N, Wagenaar-Tison A, Doyer E, Piché M. Electrophysiological investigation of the contribution of attention to altered pain inhibition processes in patients with irritable bowel syndrome. J Physiol Sci 2020; 70:46. [PMID: 33023474 PMCID: PMC10717774 DOI: 10.1186/s12576-020-00774-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 09/22/2020] [Indexed: 11/10/2022]
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with chronic abdominal pain and altered pain processing. The aim of this study was to examine whether attentional processes contribute to altered pain inhibition processes in patients with IBS. Nine female patients with IBS and nine age-/sex-matched controls were included in a pain inhibition paradigm using counter-stimulation and distraction with electroencephalography. Patients with IBS showed no inhibition of pain-related brain activity by heterotopic noxious counter-stimulation (HNCS) or selective attention. In the control group, HNCS and selective attention decreased the N100, P260 and high-gamma oscillation power. In addition, pain-related high-gamma power in sensorimotor, anterior cingulate and left dorsolateral prefrontal cortex was decreased by HNCS and selective attention in the control group, but not in patients with IBS. These results indicate that the central pain inhibition deficit in IBS reflects interactions between several brain processes related to pain and attention.
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Affiliation(s)
- Nabi Rustamov
- Department of Anatomy, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada
- CogNAC Research Group, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada
| | - Alice Wagenaar-Tison
- Department of Anatomy, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada
- CogNAC Research Group, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada
| | - Elysa Doyer
- Department of Anatomy, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada
- CogNAC Research Group, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada
| | - Mathieu Piché
- Department of Anatomy, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada.
- CogNAC Research Group, Université du Québec à Trois-Rivières, 3351 Boul. Des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada.
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11
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Goyal O, Bansal M, Sood A. Clinical and anorectal manometry profile of patients with functional constipation and constipation-predominant irritable bowel syndrome. Indian J Gastroenterol 2019; 38:211-219. [PMID: 31240564 DOI: 10.1007/s12664-019-00953-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 04/11/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) have significant healthcare impact. Clinical and investigative data of patients with these disorders in Indian population is scarce. We aimed to compare the clinical and anorectal manometric profile of patients with FC and IBS-C. METHODS Consecutive patients with chronic constipation undergoing anorectal manometry (ARM) and balloon expulsion test (BET) were enrolled. Thirty healthy volunteers served as controls (HC). Functional defecatory disorder (FDD) was diagnosed according to ROME IV criteria if both ARM and BET were abnormal. RESULTS Of the 231 patients enrolled (median age 47 years, 87.8% males), FC and IBS-C were diagnosed in 132 (57.1%) and 99 (42.9%) patients, respectively. Significant clinical differences between FC and IBS-C patients included older age, lower stool frequency/week, higher frequency of straining, and greater frequency of incomplete evacuation (p < 0.001). ARM revealed abnormal defecatory pattern in 55.3% (n = 73) FC patients and 47.5% (n = 47) IBS-C patients. Of them, 54.7% (40/73) of FC patients had inadequate defecatory propulsion while 89.4% (42/47) of the IBS-C patients had dyssynergic defecation (p < 0.001). Abnormal BET was seen in 67.4% of FC patients and 43.4% of IBS-C patients. Thus, FDD was diagnosed in 55.3% and 46.5% of FC and IBS-C patients, respectively. Rectal hyposensitivity was present in 60.6% of FC patients compared with 2% of IBS-C patients (p < 0.001). CONCLUSIONS There were significant differences in clinical and manometric profile of FC and IBS-C patients. Compared with IBS-C patients, FC patients were older, had higher prevalence of FDD, less often had dyssynergic defecation, and had higher prevalence of rectal hyposensitivity.
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Affiliation(s)
- Omesh Goyal
- Department of Gastroenterology, Dayanand Medical College and Hospital, Civil Lines, Tagore Nagar, Ludhiana 141 001, India.
| | - Monika Bansal
- Department of Gastroenterology, Dayanand Medical College and Hospital, Civil Lines, Tagore Nagar, Ludhiana 141 001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Civil Lines, Tagore Nagar, Ludhiana 141 001, India
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12
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Zhang Y, Qin G, Liu DR, Wang Y, Yao SK. Increased expression of brain-derived neurotrophic factor is correlated with visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome. World J Gastroenterol 2019; 25:269-281. [PMID: 30670915 PMCID: PMC6337018 DOI: 10.3748/wjg.v25.i2.269] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/03/2018] [Accepted: 12/13/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome (IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor (BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS (IBS-D). AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology. METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 age- and sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined. RESULTS The patients had a higher anxiety score [median (interquartile range), 6.0 (2.0-10.0) vs 3.0 (1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0 (44.0-61.0) vs 21.0 (17.3-30.0), P < 0.001] than controls. The defecating sensation threshold [60.0 (44.0-80.0) vs 80.0 (61.0-100.0), P = 0.009], maximum tolerable threshold [103.0 (90.0-128.0) vs 182.0 (142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0 (20.0-30.0) vs 30.0 (30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46E-2 (3.06E-2-4.44E-2) vs 3.07E-2 (2.91E-2-3.48E-2), P = 0.031] and mRNA [1.57 (1.31-2.61) vs 1.09 (0.74-1.42), P = 0.001] expression and nerve fiber density [4.12E-2 (3.07E-2-7.46E-2) vs 1.98E-2 (1.21E-2-4.25E-2), P = 0.002] were significantly elevated in the patients. Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters. CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.
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Affiliation(s)
- Yu Zhang
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Geng Qin
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - De-Rong Liu
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yan Wang
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shu-Kun Yao
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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13
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Rangan V, Mitsuhashi S, Singh P, Ballou S, Hirsch W, Sommers T, Nee J, Iturrino J, Lembo A. Risk Factors for Fecal Urgency Among Individuals With and Without Diarrhea, Based on Data From the National Health and Nutrition Examination Survey. Clin Gastroenterol Hepatol 2018; 16:1450-1458.e2. [PMID: 29474972 PMCID: PMC6098738 DOI: 10.1016/j.cgh.2018.02.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 01/25/2018] [Accepted: 02/11/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Fecal urgency is a common symptom among patients with gastrointestinal disorders, but can also occur in healthy individuals with normal bowel habits. There have been few studies of fecal urgency in the general population. We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) to analyze the prevalence of and risk factors for this symptom. METHODS We analyzed data from 4676 persons who completed the Bowel Health Questionnaire from the NHANES, from 2009 through 2010. The NHANES sampled a nationally representative group of adults in the United States and provides information on demographics, medical comorbidities, and dietary habits of survey participants. The Bowel Health Questionnaire provided additional information about bowel symptoms such as urgency, incontinence, constipation, and diarrhea. We identified individuals with fecal urgency and calculated differences in fecal urgency among subgroups using chi-squared analysis. We used logistic regression to identify factors associated with urgency. RESULTS In our study population, the prevalence of fecal urgency was 3.3%; 29.5% of individuals with fecal urgency had diarrhea. The prevalence of fecal urgency was significantly higher in individuals who had diarrhea (14.8%) than in individuals without diarrhea (3.1%). Older age, female sex, poverty, urinary urge incontinence, diarrhea, and increased stool frequency were all associated with fecal urgency on multivariable analysis. Decreased fiber intake and increased carbohydrate intake were associated with urgency among individuals with diarrhea. CONCLUSIONS In an analysis of data from 4676 individuals who completed a Bowel Health Questionnaire from the NHANES, we found a significantly higher proportion of individuals with diarrhea to have fecal urgency. However, most individuals with fecal urgency do not have diarrhea. Factors associated with fecal urgency vary among individuals with and without diarrhea.
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Affiliation(s)
- Vikram Rangan
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Shuji Mitsuhashi
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Prashant Singh
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Sarah Ballou
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - William Hirsch
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Thomas Sommers
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Judy Nee
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Johanna Iturrino
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Anthony Lembo
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
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14
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Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal Distension in Patients With Irritable Bowel Syndrome. Psychosom Med 2018; 79:988-999. [PMID: 28498276 DOI: 10.1097/psy.0000000000000484] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE We investigated whether certainty and uncertainty of impending aversive visceral sensation differently modulate regional brain activity, both during anticipation and visceral sensation in irritable bowel syndrome (IBS) patients compared with healthy controls. METHODS Twenty-six IBS patients (14 women) and 29 healthy controls (15 women) were enrolled in a functional magnetic resonance imaging study. Participants received rectal distention at an individually titrated severe discomfort level that was preceded by visual cues to induce certain (100% chance of distention), uncertain (50% chance), and safe (0% chance) anticipation. RESULTS Subjective ratings of anticipatory fear before and discomfort during distention were similar between IBS and control participants under cued certainty and uncertainty (p > .05). Uncertain anticipation compared with certain anticipation induced greater activation of anterior midcingulate cortex, thalamus, and visual processing areas in IBS patients compared with controls. Rectal distention after the uncertain, but not certain, cue induced higher activity in the posterior- and midcingulate cortices and the precuneus in IBS compared with controls. Controls exhibited bilateral insula activation during the nondistention period after the uncertain cue compared with the safe cue. IBS patients failed to produce this response, which was possibly due to elevated bilateral insular responses during nondistention after the safe cue. Brain data were significant at a voxel-level threshold of puncorrected value of less than .005 combined with a cluster-level threshold of pFWE-corrected value of less than .05. CONCLUSIONS Preceding uncertainty differentially modulates the brain processing of physiologically identical rectal stimulation in IBS patients. Cue-dependent alterations in brain responses may underlie hypervigilance to visceral sensations in IBS patients.
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15
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Simrén M, Törnblom H, Palsson OS, van Tilburg MAL, Van Oudenhove L, Tack J, Whitehead WE. Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts. Gut 2018; 67:255-262. [PMID: 28104632 DOI: 10.1136/gutjnl-2016-312361] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 12/16/2016] [Accepted: 01/01/2017] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. DESIGN We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. RESULTS In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). CONCLUSIONS A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.
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Affiliation(s)
- Magnus Simrén
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Hans Törnblom
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Olafur S Palsson
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Miranda A L van Tilburg
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Lukas Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - William E Whitehead
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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16
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Experimental Models of Irritable Bowel Syndrome and the Role of the Enteric Neurotransmission. J Clin Med 2018; 7:jcm7010004. [PMID: 29301333 PMCID: PMC5791012 DOI: 10.3390/jcm7010004] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 12/14/2017] [Accepted: 12/18/2017] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animal models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.
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17
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Maixner W, Fillingim RB, Williams DA, Smith SB, Slade GD. Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification. THE JOURNAL OF PAIN 2017; 17:T93-T107. [PMID: 27586833 DOI: 10.1016/j.jpain.2016.06.002] [Citation(s) in RCA: 344] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 06/01/2016] [Accepted: 06/06/2016] [Indexed: 12/26/2022]
Abstract
UNLABELLED There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs. PERSPECTIVE This brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs.
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Affiliation(s)
- William Maixner
- Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, North Carolina.
| | - Roger B Fillingim
- Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, Florida
| | - David A Williams
- Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
| | - Shad B Smith
- Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, North Carolina
| | - Gary D Slade
- Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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18
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[Brain-gut axis and gut-directed hypnosis - success of an integrated psychosomatic treatment in gastroenterology]. ZEITSCHRIFT FUR PSYCHOSOMATISCHE MEDIZIN UND PSYCHOTHERAPIE 2017; 63:5-19. [PMID: 28245719 DOI: 10.13109/zptm.2017.63.1.5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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19
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Xu XJ, Zhang YL, Liu L, Pan L, Yao SK. Increased expression of nerve growth factor correlates with visceral hypersensitivity and impaired gut barrier function in diarrhoea-predominant irritable bowel syndrome: a preliminary explorative study. Aliment Pharmacol Ther 2017; 45:100-114. [PMID: 27862119 DOI: 10.1111/apt.13848] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 07/29/2016] [Accepted: 10/09/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND Neural-immune-endocrine network mechanism has attracted increased attention in diarrhoea-predominant irritable bowel syndrome (IBS-D). Pre-clinical evidence indicates that nerve growth factor (NGF) mediates visceral hypersensitivity and gut barrier dysfunction, via interactions with mast cells and sensory nerve fibres. AIM To explore the role of nerve growth factor, as well as mast cell-nerve growth factor-nerve interaction in IBS-D pathophysiology. METHODS In this cross-sectional study, IBS-D patients and healthy controls first underwent clinical and psychological assessments. Visceral sensitivity to rectal distension was tested. As gut barrier function markers, serum diamine oxidase and d-lactate were detected. Rectosigmoid biopsies were taken for the analyses of nerve growth factor expression, mast cell count and activation, and sensory nerve fibres expressing transient receptor potential vanilloid 1 and calcitonin gene-related peptide. Correlations between these parameters were examined in patients. RESULTS Thirty-eight IBS-D patients (28 males, 10 females; average age 30.2 years) and 20 healthy controls (12 males, 8 females; average age 26.8 years) participated in the study. The patients presented increased psychological symptoms, visceral hypersensitivity and impaired gut barrier function. NGF gene expression, mast cell count and sensory nerve fibres were significantly increased in the patients (P < 0.05). In correlation analysis, NGF expression was positively correlated with the disease severity, anxiety and serum diamine oxidase; visceral sensitivity thresholds were negatively associated with NGF expression (Bonferroni corrected P < 0.0029). CONCLUSIONS Elevated mucosal NGF may interact with mast cells and sensory nerve fibres, contributing to visceral hypersensitivity and impaired gut barrier function in IBS-D.
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Affiliation(s)
- X J Xu
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Gastroenterology Department, China-Japan Friendship Hospital, Beijing, China
| | - Y L Zhang
- Gastroenterology Department, China-Japan Friendship Hospital, Beijing, China
| | - L Liu
- Jinan Central Hospital Affiliated to Shandong University, Jinan, China
| | - L Pan
- Immunohistochemistry Laboratory of Clinical Medical Research Institute, China-Japan Friendship Hospital, Beijing, China
| | - S K Yao
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Gastroenterology Department, China-Japan Friendship Hospital, Beijing, China
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20
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Scanzi J, Accarie A, Muller E, Pereira B, Aissouni Y, Goutte M, Joubert-Zakeyh J, Picard E, Boudieu L, Mallet C, Gelot A, Ardid D, Carvalho FA, Dapoigny M. Colonic overexpression of the T-type calcium channel Ca v 3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients. Neurogastroenterol Motil 2016; 28:1632-1640. [PMID: 27196538 DOI: 10.1111/nmo.12860] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 04/22/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. METHODS This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression. KEY RESULTS Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. CONCLUSIONS & INFERENCES This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.
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Affiliation(s)
- J Scanzi
- Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France. .,Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
| | - A Accarie
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - E Muller
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - B Pereira
- Centre Hospitalier Universitaire G. Montpied, Biostatistics Unit (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Y Aissouni
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - M Goutte
- Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - J Joubert-Zakeyh
- Centre Hospitalier Universitaire Estaing, Department of Histopathology, CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France
| | - E Picard
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - L Boudieu
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - C Mallet
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - A Gelot
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - D Ardid
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - F A Carvalho
- Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
| | - M Dapoigny
- Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France.,Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
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21
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Traini C, Evangelista S, Girod V, Faussone-Pellegrini MS, Vannucchi MG. Changes of excitatory and inhibitory neurotransmitters in the colon of rats underwent to the wrap partial restraint stress. Neurogastroenterol Motil 2016; 28:1172-85. [PMID: 26972279 DOI: 10.1111/nmo.12816] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 02/09/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND Animal models proposed to reproduce some of the human irritable bowel syndrome (IBS) symptoms are based on the hypothesis that psychosocial stressors play a pivotal role in the IBS etio-pathology. We investigated the wrap restraint stress (WRS) model with the aim to analyze the morphological changes of the entire colonic wall of these animals that showed some of the human IBS symptoms such as visceral hypersensitivity. METHODS Male Wistar rats were used and WRS was maintained for 2 h. Abdominal contractions (AC) were recorded in the colon-rectum by balloon distension. Fecal pellets were quantitated. Colonic specimens were examined by routine histology, immunohistochemistry and western blot. KEY RESULTS WRS animals were characterized by: (i) increase in AC number and fecal pellets mean weight; (ii) clusters of mononucleated cells, increase in eosinophilic granulocytes and mast cells in the mucosa; (iii) increase in CGRP-immunoreactive (IR) nerve fibers in the lamina propria; (iv) decrease in myenteric NK1r-IR and nNOS-IR neurons and in submucous nNOS-IR neurons; (v) decrease in SP-IR nerve fibers in the muscle wall; (vi) reduction in S100β-IR glia in the entire colonic wall; (vii) increase in CRF1r-IR myenteric neurons; (viii) no change in ChAT-IR neurons, smooth muscle cells and interstitial cells of Cajal. CONCLUSIONS AND INFERENCES The present results support the consistency of the WRS as a potential model where part of the human IBS signs and symptoms are reproduced. The changes in glial cells and in excitatory and inhibitory neurotransmitters might represent the substrate for the dysmotility and hypersensitivity.
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Affiliation(s)
- C Traini
- Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, University of Florence, Florence, Italy
| | - S Evangelista
- Menarini Ricerche SpA, Preclinical Development, Florence, Italy
| | - V Girod
- Syncrosome, Marseille, France
| | - M S Faussone-Pellegrini
- Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, University of Florence, Florence, Italy
| | - M G Vannucchi
- Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, University of Florence, Florence, Italy
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22
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Abstract
The symptom-based diagnosis of irritable bowel syndrome (IBS) has not been established in everyday clinical practice, and the diagnosis of this disorder remains one of exclusion. It has been demonstrated that the densities of duodenal chromogranin A, rectal peptide YY and somatostatin cells are good biomarkers for the diagnosis of sporadic IBS, and low-grade mucosal inflammation is a promising biomarker for the diagnosis of postinfectious IBS. Genetic markers are not useful as biomarkers for IBS since the potential risk genes have yet to be validated, and the intestinal microbiota cannot be used because of the lack of an association between a specific bacterial species and IBS. Furthermore, gastrointestinal dysmotility and visceral hypersensitivity tests produce results that are too nonconsistent and noncharacteristic to be used in the diagnosis of IBS. A combination of symptom-based assessment, exclusion of overlapping gastrointestinal diseases and positive biomarkers appears to be the best way to diagnose IBS.
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Affiliation(s)
- Magdy El-Salhy
- a Department of Medicine, Section for Gastroenterology, Stord Hospital, Stord, Norway
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23
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Rao SS, Bharucha AE, Chiarioni G, Felt-Bersma R, Knowles C, Malcolm A, Wald A. Functional Anorectal Disorders. Gastroenterology 2016; 150:S0016-5085(16)00175-X. [PMID: 27144630 PMCID: PMC5035713 DOI: 10.1053/j.gastro.2016.02.009 10.1053/j.gastro.2016.02.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 02/09/2016] [Indexed: 01/11/2024]
Abstract
This report defines criteria and reviews the epidemiology, pathophysiology, and management of common anorectal disorders: fecal incontinence (FI), functional anorectal pain and functional defecation disorders. FI is defined as the recurrent uncontrolled passage of fecal material for at least 3 months. The clinical features of FI are useful for guiding diagnostic testing and therapy. Anorectal manometry and imaging are useful for evaluating anal and pelvic floor structure and function. Education, antidiarrheals and biofeedback therapy are the mainstay of management; surgery may be useful in refractory cases. Functional anorectal pain syndromes are defined by clinical features and categorized into three subtypes. In proctalgia fugax, the pain is typically fleeting and lasts for seconds to minutes. In levator ani syndrome (LAS) and unspecified anorectal pain the pain lasts more than 30 minutes, but in LAS there is puborectalis tenderness. Functional defecation disorders are defined by >2 symptoms of chronic constipation or irritable bowel syndrome with constipation, and with >2 features of impaired evacuation i.e., abnormal evacuation pattern on manometry, abnormal balloon expulsion test or impaired rectal evacuation by imaging. It includes two subtypes; dyssynergic defecation and inadequate defecatory propulsion. Pelvic floor biofeedback therapy is effective for treating LAS and defecatory disorders.
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24
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Rao SS, Bharucha AE, Chiarioni G, Felt-Bersma R, Knowles C, Malcolm A, Wald A. Functional Anorectal Disorders. Gastroenterology 2016; 150:S0016-5085(16)00175-X. [PMID: 27144630 PMCID: PMC5035713 DOI: 10.1053/j.gastro.2016.02.009] [Citation(s) in RCA: 313] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 02/09/2016] [Indexed: 12/12/2022]
Abstract
This report defines criteria and reviews the epidemiology, pathophysiology, and management of common anorectal disorders: fecal incontinence (FI), functional anorectal pain and functional defecation disorders. FI is defined as the recurrent uncontrolled passage of fecal material for at least 3 months. The clinical features of FI are useful for guiding diagnostic testing and therapy. Anorectal manometry and imaging are useful for evaluating anal and pelvic floor structure and function. Education, antidiarrheals and biofeedback therapy are the mainstay of management; surgery may be useful in refractory cases. Functional anorectal pain syndromes are defined by clinical features and categorized into three subtypes. In proctalgia fugax, the pain is typically fleeting and lasts for seconds to minutes. In levator ani syndrome (LAS) and unspecified anorectal pain the pain lasts more than 30 minutes, but in LAS there is puborectalis tenderness. Functional defecation disorders are defined by >2 symptoms of chronic constipation or irritable bowel syndrome with constipation, and with >2 features of impaired evacuation i.e., abnormal evacuation pattern on manometry, abnormal balloon expulsion test or impaired rectal evacuation by imaging. It includes two subtypes; dyssynergic defecation and inadequate defecatory propulsion. Pelvic floor biofeedback therapy is effective for treating LAS and defecatory disorders.
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25
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Grinsvall C, Törnblom H, Tack J, Van Oudenhove L, Simrén M. Psychological factors selectively upregulate rectal pain perception in hypersensitive patients with irritable bowel syndrome. Neurogastroenterol Motil 2015; 27:1772-82. [PMID: 26467837 DOI: 10.1111/nmo.12689] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 08/25/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Visceral hypersensitivity and psychological symptoms are frequent features in irritable bowel syndrome (IBS). Exploring mechanistic pathways leading to visceral hypersensitivity is of importance to direct future studies and treatment options. In this study, we evaluated the contribution of psychological factors to the perception of painful and non-painful rectal sensations in hyper- vs normosensitive IBS patients. METHODS We included 138 IBS patients (Rome II criteria) who underwent an ascending method of limited rectal balloon distension paradigm. At the end of each distension step, subjects rated the perceived intensity of non-painful ('unpleasantness') and painful rectal sensations on visual analog scales. Sensitivity status was determined based on pain thresholds. Anxiety, depression and somatization were assessed by questionnaires. Mixed models were used to test the relationship between sensitivity status, psychological variables, and pain & unpleasantness ratings upon increasing distension. KEY RESULTS Hypersensitive IBS patients had lower sensory thresholds for pain, first perception, urge to defecate, and discomfort (p < 0.0001). Upon increasing distension, they rated both painful and non-painful sensations as more intense than normosensitive patients (p < 0.0001). Psychological factors were associated with higher pain ratings during distension in hypersensitive (p < 0.006-0.0001), but not in normosensitive patients. Anxiety, but not depression or somatization, was associated with increased intensity ratings of non-painful sensations (p < 0.001), independent of sensitivity status. CONCLUSIONS & INFERENCES Hypersensitive IBS patients are characterized by increased perception of pain, but also of non-painful sensations. Psychological factors increase the perception of painful sensations in hypersensitive patients only, whereas non-painful visceral sensations were exaggerated in anxious patients regardless of the sensitivity status.
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Affiliation(s)
- C Grinsvall
- Dept of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,University of Gothenburg Centre for Person-Centered Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - H Törnblom
- Dept of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,University of Gothenburg Centre for Person-Centered Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - J Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - L Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - M Simrén
- Dept of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,University of Gothenburg Centre for Person-Centered Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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26
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Cenac N, Castro M, Desormeaux C, Colin P, Sie M, Ranger M, Vergnolle N. A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice. Eur J Pain 2015; 20:723-30. [PMID: 26541237 DOI: 10.1002/ejp.798] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Trimebutine maleate, a noncompetitive spasmolytic agent with some affinity for peripheral μ- and κ-opioid receptors has been evaluated as a treatment in a limited number of patients undergoing sedation-free full colonoscopy. The efficiency of such treatment was comparable to sedation-based colonoscopies to relieve from pain and discomfort. METHODS A new and improved trimebutine salt capable of releasing in vivo hydrogen sulphide (H2S), a gaseous mediator known to reduce nociception, has been developed. This drug salt (GIC-1001) is composed of trimebutine bearing a H2S-releasing counterion (3-thiocarbamoylbenzoate, 3TCB), the latter having the ability to release H2S. GIC-1001 has been tested here in a mouse model of colorectal distension. RESULTS In mice, while orally given trimebutine (the maleate salt, non-H2 S-releaser) only slightly reduced the nociceptive response to increasing pressures of colorectal distension, oral administration of GIC-1001 (the H2S-releaser) was able to significantly reduce nociceptive response to all noxious stimuli, in a dose-dependent manner. This effect of GIC-1001 was significantly better than the effects of its parent compound trimebutine administered at equimolar doses. CONCLUSIONS Taken together, these results demonstrated increased antinociceptive properties for GIC-1001 compared to trimebutine, suggesting that this compound would be a better option to relieve from visceral pain and discomfort induced by lumenal distension.
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Affiliation(s)
- N Cenac
- INSERM U1043, Toulouse, France
- CNRS U5282, Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France
| | - M Castro
- INSERM U1043, Toulouse, France
- CNRS U5282, Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France
| | - C Desormeaux
- INSERM U1043, Toulouse, France
- CNRS U5282, Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France
| | - P Colin
- GIcare pharma Inc, Montréal, Canada
| | - M Sie
- INSERM U1043, Toulouse, France
- CNRS U5282, Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France
| | - M Ranger
- GIcare pharma Inc, Montréal, Canada
| | - N Vergnolle
- INSERM U1043, Toulouse, France
- CNRS U5282, Toulouse, France
- Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, France
- Department of Physiology and Pharmacology, University of Calgary, Canada
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27
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Mujagic Z, Keszthelyi D, Aziz Q, Reinisch W, Quetglas EG, De Leonardis F, Segerdahl M, Masclee AAM. Systematic review: instruments to assess abdominal pain in irritable bowel syndrome. Aliment Pharmacol Ther 2015; 42:1064-81. [PMID: 26290286 DOI: 10.1111/apt.13378] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Revised: 02/02/2015] [Accepted: 07/31/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Consensus on standard methods to assess chronic abdominal pain in patients with irritable bowel syndrome (IBS) is currently lacking. AIM To systematically review the literature with respect to instruments of measurement of chronic abdominal pain in IBS patients. METHODS Systematic literature search was performed in PubMed/Medline databases for studies using pain measurement instruments in patients with IBS. RESULTS One hundred and ten publications were reviewed. A multitude of different instruments is currently used to assess chronic abdominal pain in IBS patients. The single-item methods, e.g. the validated 10-point numeric rating scale (NRS), and questionnaires assessing gastrointestinal symptoms severity, focus mostly on the assessment of only the intensity of abdominal pain. Of these questionnaires, the validated IBS-Symptom Severity Scale includes the broadest measurement of pain-related aspects. General pain questionnaires and electronic momentary symptom assessment tools have been used to study abdominal pain in IBS patients, but have not yet been validated for this purpose. The evidence for the use of provocation tests, e.g. the rectal barostat with balloon distention, for measurement of abdominal pain in IBS is weak, due to the poor correlation between visceral pain thresholds assessed by provocation tests and abdominal pain as assessed by retrospective questionnaires. CONCLUSIONS The multitude of different instruments to measure chronic abdominal pain in IBS makes it difficult to compare endpoints of published studies. There is need for validated instruments to assess chronic abdominal pain in IBS patients, that overcome the limitations of the currently available methods.
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Affiliation(s)
- Z Mujagic
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - D Keszthelyi
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Q Aziz
- Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - W Reinisch
- Department Internal Medicine III, Medical University of Vienna, Vienna, Austria.,McMaster University, Hamilton, ON, Canada
| | - E G Quetglas
- Medical Intelligence, Early Clinical Development, Grünenthal GmBH, Aachen, Germany
| | - F De Leonardis
- Medical Intelligence, Early Clinical Development, Grünenthal GmBH, Aachen, Germany
| | - M Segerdahl
- Medical Intelligence, Early Clinical Development, Grünenthal GmBH, Aachen, Germany.,Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
| | - A A M Masclee
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
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28
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Padhy SK, Sahoo S, Mahajan S, Sinha SK. Irritable bowel syndrome: Is it "irritable brain" or "irritable bowel"? J Neurosci Rural Pract 2015; 6:568-77. [PMID: 26752904 PMCID: PMC4692018 DOI: 10.4103/0976-3147.169802] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Irritable bowel syndrome (IBS) has been recognized as one of the most common and best studied disorders among the group of functional gastrointestinal disorders. It is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit. In the Western world, IBS appears to affect up to 20% of the population at any given time but in Asian countries, the median value of IBS prevalence defined by various criteria ranges between 6.5% and 10.1%, and community prevalence of 4% is found in North India. Those attending gastroenterology clinics represent only the tip of the iceberg. The disorder substantially impairs the quality of life, and the overall health-care costs are high. IBS has therefore gained increased attention from clinicians, researchers, and pharmaceutical industries. It is often frustrating to both patients and physicians as the disease is usually chronic in nature and difficult to treat. However, the understanding of IBS has been changing from time to time and still most of its concepts are unknown. In this review we have discussed, debated, and synthesized the evidence base, focusing on underlying mechanisms in the brain and bowel. We conclude that it is both brain and bowel mechanisms that are responsible. The clinical implication of such mechanisms is discussed.
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Affiliation(s)
- Susanta Kumar Padhy
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Swapnajeet Sahoo
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sonali Mahajan
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Saroj Kumar Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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29
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Hubbard CS, Hong JY, Jiang Z, Ebrat B, Suyenobu B, Smith S, Heendeniya N, Naliboff BD, Tillisch K, Mayer EA, Labus JS. Increased attentional network functioning related to symptom severity measures in females with irritable bowel syndrome. Neurogastroenterol Motil 2015; 27:1282-94. [PMID: 26087779 PMCID: PMC4550526 DOI: 10.1111/nmo.12622] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2015] [Accepted: 05/24/2015] [Indexed: 01/09/2023]
Abstract
BACKGROUND Increased attention to gastrointestinal (GI) symptoms and disease-specific contexts may play an important role in the enhanced perception of visceral stimuli frequently reported in patients with irritable bowel syndrome (IBS). In this study, we test the hypothesis that altered attentional mechanisms underlie central pain amplification in IBS. METHODS To evaluate brain networks that support alerting, orienting, and executive attention, we employed the attention network test (ANT), a modified flanker task which measures the efficiency of functioning of core attentional networks, during functional magnetic resonance imaging in 15 IBS patients (mean age = 31 [11.96]) and 14 healthy controls (HCs; mean age = 31 [10.91]). KEY RESULTS Patients with IBS, compared to HCs, showed shorter reaction times during the alerting and orienting conditions which were associated with greater activation of anterior midcingulate and insular cortices, and decreased activity in the right inferior frontal junction and supplementary motor cortex. Patients also showed activation in the dorsal medial prefrontal cortex and concurrent thalamic deactivation during the executive control portion of the ANT relative to HCs, but no group difference in reaction times were found. The activity in brain regions showing group differences during the ANT were associated with measures of GI-specific anxiety, pain catastrophizing, and fear of uncertainty. In IBS, activity in the anterior midcingulate during alerting correlated with duration of GI-symptoms and overall symptom severity. CONCLUSIONS & INFERENCES Together, these results suggest that IBS patients have specific abnormalities in attentional network functioning and these deficits may underlie symptom-related anxiety, hypervigilance, and visceral hypersensitivity.
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Affiliation(s)
- Catherine S. Hubbard
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA,Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD,Center for Pain and the Brain, Boston Children’s Hospital
| | - Jui-Yang Hong
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA,Department of Biomedical Engineering, UCLA, Los Angeles, CA,Pain and Interoceptive Network (PAIN)
| | - Zhiguo Jiang
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA
| | - Bahar Ebrat
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA
| | - Brandall Suyenobu
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA
| | - Suzanne Smith
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA
| | - Nuwanthi Heendeniya
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA
| | - Bruce D. Naliboff
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA,VA Greater Los Angeles Healthcare System, Los Angeles, CA,Pain and Interoceptive Network (PAIN)
| | - Kirsten Tillisch
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA,Pain and Interoceptive Network (PAIN)
| | - Emeran A. Mayer
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA,Department of Physiology, UCLA, Los Angeles, CA,Department of Psychiatry, UCLA, Los Angeles, CA,Pain and Interoceptive Network (PAIN)
| | - Jennifer S. Labus
- Gail and Gerald Oppenheimer Family Center for the Neurobiology of Stress, Los Angeles, CA,Department of Medicine, UCLA, Los Angeles, CA,Department of Psychiatry, UCLA, Los Angeles, CA,Pain and Interoceptive Network (PAIN)
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30
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Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model. Dig Dis Sci 2015; 60:2316-26. [PMID: 25963324 DOI: 10.1007/s10620-015-3695-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Accepted: 04/29/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome. AIMS We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility. METHODS Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system. RESULTS Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody. CONCLUSIONS The colonic hypermotility induced by repeated WAS may be associated with the increased expression of endogenous BDNF and TrkB. BDNF may have potential clinical therapeutic use in modulating gut motility.
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Tominaga K, Tsumoto C, Ataka S, Mizuno K, Takahashi K, Yamagami H, Tanigawa T, Kawabe J, Watanabe T, Fujiwara Y, Shiomi S, Watanabe Y, Arakawa T. Regional brain disorders of serotonin neurotransmission are associated with functional dyspepsia. Life Sci 2015; 137:150-7. [PMID: 26232557 DOI: 10.1016/j.lfs.2015.07.023] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 06/19/2015] [Accepted: 07/25/2015] [Indexed: 12/12/2022]
Abstract
AIMS To elucidate the role of cerebral serotonin neurotransmission in visceral perception in functional dyspepsia (FD), we observationally examined the regional expression level of the serotonin transporter (SERT) and its correlation with clinical symptoms. MAIN METHODS FD patients (Rome III criteria; N=9, age range: 36-76years) and healthy controls (N=8, age range: 25-61years) participated in this study. Positron emission tomography scanning with [(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([(11)C]DASB), which binds specifically to SERT, was used to quantify the binding potential (BPND) of [(11)C]DASB in the midbrain, thalamus, caudate, putamen, amygdala, and hippocampus with reference to co-registered magnetic resonance images. Clinical symptoms were assessed using the Gastrointestinal Symptoms Rating Scale (GSRS). Self-Rating Depression Scale (SDS), and State-Trait Anxiety Inventory (STAI). KEY FINDINGS BPND of the midbrain (P=0.041) and thalamus (P=0.031) was higher in FD patients than in controls. The BPND values in the midbrain correlated with total GSRS (r=0.663, P=0.004) and abdominal pain (r=0.419, P=0.047) scores. Its values in the thalamus correlated with total GSRS (r=0.423, P=0.044), abdominal pain (r=0.502, P=0.022), and indigestion (r=0.476, P=0.028) scores. Its value in the hippocampus correlated with abdominal pain and state-STAI scores (r=0.528, P=0.017; r=0.428, P=0.043). SIGNIFICANCE Up-regulation of the SERT level in the midbrain and thalamus may underlie the pathogenesis of FD such as abdominal and psychological symptoms via a brain-gut interaction.
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Affiliation(s)
- Kazunari Tominaga
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
| | - Chikako Tsumoto
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Suzuka Ataka
- Department of Geriatric Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Kei Mizuno
- Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Japan; Department of Medical Science on Fatigue, Osaka City University Graduate School of Medicine, Japan
| | - Kayo Takahashi
- Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Japan
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Joji Kawabe
- Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Susumu Shiomi
- Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Japan
| | - Yasuyoshi Watanabe
- Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Japan; Department of Physiology, Osaka City University Graduate School of Medicine, Japan
| | - Tetsuo Arakawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
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The importance of a person-centered approach in diagnostic workups of patients with irritable bowel syndrome: a qualitative study. Gastroenterol Nurs 2015; 36:443-51. [PMID: 24304529 DOI: 10.1097/sga.0000000000000011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The aim of this study was to explore experiences of undergoing a diagnostic workup in patients with irritable bowel syndrome (IBS) at a unit for functional gastrointestinal disorders. Research has been sparse in addressing such experiences and the impact on well-being. Patients with IBS were invited to perform a workup of gastrointestinal tests. Of 120 patients who completed the tests, 20 were invited for an interview. Analysis of interviews was conducted through interpretative phenomenological analysis. One master theme emerged: validation of IBS experience inferred from three subthemes: the duality of suffering in IBS, coping with inflicted discomfort and pain, and capacity for resilience.Patients reported long-term suffering from symptoms including poor management within the healthcare organization. Despite inconvenience associated with the tests, patients expressed appreciation for professional attributes such as attentiveness that were perceived as a sense of being cared for and seen as a "person." During the workup, patients acquired greater knowledge of what IBS means, including knowledge about their own body functions and experienced relief that symptoms were not caused by any "dangerous" disease. Validation of IBS experience surfaced in the data implying that in such context, patients with IBS appear to find personal solutions to cope with everyday experiences and enhance autonomy.
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Zhu Y, Wu Z, Ma X, Liu H, Bao C, Yang L, Cui Y, Zhou C, Wang X, Wang Y, Zhang Z, Zhang H, Jia H, Wu H. Brain regions involved in moxibustion-induced analgesia in irritable bowel syndrome with diarrhea: a functional magnetic resonance imaging study. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 14:500. [PMID: 25516481 PMCID: PMC4301658 DOI: 10.1186/1472-6882-14-500] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 12/10/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Moxibustion is one of the most commonly used therapies in acupuncture practice, and is demonstrated to be beneficial for patients with diarrhea from irritable bowel syndrome (D-IBS). But its mechanism remains unclear. Because visceral hypersensitivity in IBS patients has been documented by evaluation of perceived stimulations through functional magnetic resonance imaging (fMRI) studies, we focused on observing brain imaging changes in D-IBS patients during rectal balloon distention before and after moxibustion in order to reveal its possible central mechanism and further evaluate its effect. METHODS This clinical trial is registered under the number: ChiCTR-TRC-10000887. Eighty D-IBS patients were randomly divided into a moxibustion and sham moxibustion group (control group) for a 4-week treatment. Fifteen patients in moxibustion group and thirteen patients in control group completed two fMRI scans during a 50 and 100 ml rectal balloon distention before and after treatment. Rectal pain were obtained with a scan test. Birmingham IBS Symptom Scale and IBS Quality of Life (QOL) Scale were used to evaluate therapeutic effect. RESULTS After treatment, the decrease in Birmingham IBS Symptom Scale and IBS QOL Scale scores in moxibustion group was significantly greater than that of control group (P < 0.01). The defecation urge threshold and the pain perception threshold of moxibustion group was also significantly higher after treatment than that of control group (P < 0.01). The decrease in pain score during the 100 ml rectal balloon distention in moxibustion group was significantly greater than that of control group (P < 0.05). There was no definite activated center during the 50 ml rectal distention in either group before treatment. After treatment, the prefrontal cortex (PFC) was affected in moxibustion group, while the PFC and the anterior cingulated cortex (ACC) were affected in control group. During the 100 ml distention before treatment in both groups, the PFC and ACC were activated. After treatment, they disappeared in moxibustion group but remained in control group. CONCLUSIONS Moxibustion can improve symptoms and quality of life in D-IBS patients. It can also decrease rectal sensitivity. The activation of PFC and ACC during a 100 ml rectal distention disappeared after moxibustion treatment.
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Abstract
With more than 100 studies published over the past two decades, functional brain imaging research in gastroenterology has become an established field; one that has enabled improved insight into the supraspinal responses evoked by gastrointestinal stimulation both in health and disease. However, there remains considerable inter-study variation in the published results, largely owing to methodological differences in stimulation and recording techniques, heterogeneous patient selection, lack of control for psychological factors and so on. These issues with reproducibility, although not unique to studies of the gastrointestinal tract, can lead to unjustified inferences. To obtain consistent and more clinically relevant results, there is a need to optimize and standardize brain imaging studies across different centres. In addition, the use of complementary and more novel brain imaging modalities and analyses, which are now being used in other fields of research, might help unravel the factors at play in functional gastrointestinal disorders. This Review highlights the areas in which functional brain imaging has been useful and what it has revealed, the areas that are in need of improvement, and finally suggestions for future directions.
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EL-SALHY MAGDY, GILJA ODDHELGE, GUNDERSEN DORIS, HATLEBAKK JANG, HAUSKEN TRYGVE. Interaction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (review). Int J Mol Med 2014; 34:363-71. [PMID: 24939595 PMCID: PMC4094590 DOI: 10.3892/ijmm.2014.1811] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 02/10/2014] [Indexed: 12/15/2022] Open
Abstract
Several endocrine cell abnormalities have been reported in different segments of the gastrointestinal tract of patients with irritable bowel syndrome (IBS). These cells have specialized microvilli that project into the lumen; they function as sensors for the gut contents and respond to luminal stimuli (mostly ingested nutrients) by releasing hormones into the lamina propria, where they exert their effects via a paracrine/endocrine mode of action. Certain food items trigger the symptoms experienced by IBS patients, including those rich in fermentable oligo-, di- and monosaccharides, and polyols (FODMAPs). In this review, we present the argument that the effects of both FODMAPs and the proportional intake of proteins, fats and carbohydrates on IBS symptoms may be caused by an interaction with the gut endocrine cells. Since the gut hormones control and regulate gastrointestinal motility and sensation, this interaction may be responsible for abnormal gastrointestinal motility and the visceral hypersensitivity observed in these patients. There is no consistent evidence that IBS patients suffer from food allergy. The role of gluten intolerance in the development of IBS symptoms in these patients remains a matter of controversy. Individual guidance on food management, which includes restrictions in the intake of FODMAP-rich foods and testing diets with different proportions of proteins, fats and carbohydrates has been found to reduce the symptoms, improve the quality of life, and make the habitual diet of IBS patients more healthy.
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Affiliation(s)
- MAGDY EL-SALHY
- Section of Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, University of Bergen, Bergen, Norway
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - ODD HELGE GILJA
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | | | - JAN G. HATLEBAKK
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - TRYGVE HAUSKEN
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Posserud I, Strid H, Störsrud S, Törnblom H, Svensson U, Tack J, Van Oudenhove L, Simrén M. Symptom pattern following a meal challenge test in patients with irritable bowel syndrome and healthy controls. United European Gastroenterol J 2014; 1:358-67. [PMID: 24917984 DOI: 10.1177/2050640613501817] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 07/17/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Patients with irritable bowel syndrome (IBS) often complain of worsening of symptoms after meal intake. Meal challenge tests have previously been used to study symptoms and pathophysiology in functional dyspepsia. OBJECTIVE The objective of this article is to evaluate differences in gastrointestinal (GI) symptom response to a standardized meal test in IBS compared to healthy controls. METHODS We included 67 patients with IBS and 16 healthy controls. After an overnight fast the subjects were served breakfast (540 kcal; 36% fat, 15% proteins, 49% carbohydrates; 8.9 g fiber). They completed visual analog scales assessing severity of six GI symptoms (abdominal pain, bloating, discomfort, nausea, gas, fullness) before breakfast and every 30 minutes up to 240 minutes after breakfast. The patients also completed a questionnaire (IBS-SSS) to assess IBS symptom severity during the preceding week. The course of symptom scores over time was analyzed using mixed models. RESULTS The meal was well tolerated and all subjects completed the test period. In patients, significant effects of time (initial increase to a maximum, followed by a return to baseline) were found for fullness, bloating, nausea and discomfort (all p values < 0.01 for linear, quadratic and third-order effect of time). In IBS patients, an independent significant association between IBS-SSS scores and all postprandial symptoms, except for nausea, was found (all p < 0.01). In controls, a significant linear, quadratic and third-order effect of time (all p < 0.0001) was found for fullness only. The difference in time course for bloating and discomfort between IBS patients and controls was confirmed when comparing the groups directly (significant time-by-group interaction effects, all p < 0.05), but not for nausea. On average, IBS patients scored significantly higher than controls on all symptoms, except for nausea (significant main effects of group, all p < 0.05). CONCLUSIONS A standardized meal test seems to be a promising tool to study the symptom pattern in IBS and potentially to follow the effect of interventions.
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Affiliation(s)
- Iris Posserud
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hans Strid
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Stine Störsrud
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; University of Gothenburg Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hans Törnblom
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; University of Gothenburg Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium
| | - Lukas Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium
| | - Magnus Simrén
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; University of Gothenburg Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Cuntz U. Grundkonzepte der gastrointestinalen Psychophysiologie. VERHALTENSTHERAPIE 2014. [DOI: 10.1159/000362913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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van der Veek SMC, Derkx BHF, Plak RD, Benninga MA, Boer F, Lindauer RJL, de Haan E. Attentional Bias to Activity of Different Parts of the Body in Children With Functional Abdominal Pain: An Experimental Study. J Pediatr Psychol 2014; 39:438-49. [DOI: 10.1093/jpepsy/jsu004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Lindfors P, Ljótsson B, Bjornsson E, Abrahamsson H, Simrén M. Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome. Neurogastroenterol Motil 2013; 25:169-e86. [PMID: 23051178 DOI: 10.1111/nmo.12022] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gut-directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. METHODS We evaluated 83 patients with IBS treated with gut-directed hypnotherapy (1 h week(-1), 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment. KEY RESULTS After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non-responder group. CONCLUSIONS & INFERENCES Patient satisfaction with gut-directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option.
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Affiliation(s)
- P Lindfors
- Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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Bueno L, Beaufrand C, Theodorou V, Andro-Delestrain MC. Influence of simethicone and alverine on stress-induced alterations of colonic permeability and sensitivity in rats: beneficial effect of their association. J Pharm Pharmacol 2013; 65:567-73. [PMID: 23488786 DOI: 10.1111/jphp.12021] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2012] [Accepted: 11/30/2012] [Indexed: 01/12/2023]
Abstract
OBJECTIVES Alverine, an antispasmodic agent for the treatment of irritable bowel syndrome (IBS), may be combined with simethicone, a protective agent of the mucosa. Stress is a major factor triggering abdominal pain in IBS and causing hypersensitivity to colonic distension in animals through an increased colonic permeability. The antinociceptive effects of alverine and simethicone, separately or in association, were evaluated on stress-induced colonic hypersensitivity to distension in rats. The influence of simethicone on altered permeability was also tested. METHODS Groups of 8-10 female adult Wistar rats (200-250 g) housed individually were used. Gut paracellular permeability was evaluated after 2 h of partial restraint stress using oral gavage with ⁵¹Cr-EDTA and 24 h of urine collection. The number of abdominal cramps during colonic distension was evaluated in animals equipped with electrodes on their abdominal striated muscles. KEY FINDINGS At 200 mg/kg p.o. twice a day, but not at lower doses, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. Administered alone at 10 mg/kg p.o., alverine also reduced stress-induced hypersensitivity to distension; lower doses were inactive. However, alverine administered at an inactive dose with simethicone suppressed stress-induced hypersensitivity to distension. CONCLUSIONS We conclude that both simethicone and alverine have visceral antinociceptive effects by two different mechanisms and that simethicone exerts a potentiating effect on the antinociceptive action of alverine.
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Affiliation(s)
- Lionel Bueno
- Department of Neurogastroenterology, Toxalim- INRA, Toulouse, France.
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Lackner JM, Jaccard J, Baum C. Multidomain patient-reported outcomes of irritable bowel syndrome: exploring person-centered perspectives to better understand symptom severity scores. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2013; 16:97-103. [PMID: 23337220 PMCID: PMC3558994 DOI: 10.1016/j.jval.2012.08.2207] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Revised: 07/19/2012] [Accepted: 08/23/2012] [Indexed: 06/01/2023]
Abstract
OBJECTIVES Patient-reported outcomes assessing multiple gastrointestinal symptoms are central to characterizing the therapeutic benefit of novel agents for irritable bowel syndrome (IBS). Common approaches that sum or average responses across different illness components must be unidimensional and have small unique variances to avoid aggregation bias and misinterpretation of clinical data. This study sought to evaluate the unidimensionality of the IBS Symptom Severity Scale (IBS-SSS) and to explore person-centered cluster analytic methods for characterizing multivariate-based patient profiles. METHODS Ninety-eight Rome-diagnosed patients with IBS completed the IBS-SSS and a single, global item of symptom severity (UCLA Symptom Severity Scale) at pretreatment baseline of a clinical trial funded by the National Institutes of Health. k-means cluster analyses were performed on participants' symptom severity scores. RESULTS The IBS-SSS was not unidimensional. Exploratory cluster analyses revealed four common symptom profiles across five items of the IBS-SSS. One cluster of patients (25%) had elevated scores on pain frequency and bowel dissatisfaction, with less elevated but still high scores on life interference and low pain severity ratings. A second cluster (19%) was characterized by intermediate scores on both pain dimensions but more elevated scores on bowel dissatisfaction. A third cluster (18%) had elevated scores across all IBS-SSS subcomponents. The fourth and the most common cluster (37%) had relatively low scores on all dimensions except bowel dissatisfaction and life interference due to IBS symptoms. CONCLUSIONS Patient-reported outcome end points and research on IBS more generally relying on multicomponent assessments of symptom severity should take into account the multidimensional structure of symptoms to avoid aggregation bias and to optimize the sensitivity of detecting treatment effects.
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Affiliation(s)
- Jeffrey M Lackner
- Division of Gastroenterology, Department of Medicine, University at Buffalo School of Medicine, SUNY, Buffalo, NY 14215, USA.
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Almansa C, Agrawal A, Houghton LA. Intestinal microbiota, pathophysiology and translation to probiotic use in patients with irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2012; 6:383-98. [PMID: 22646259 DOI: 10.1586/egh.12.9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Probiotic agents have received growing attention in recent years as an alternative therapeutic tool in the management of irritable bowel syndrome. In this article, we will discuss the rationale that support this indication, including the role of intestinal microbiota in gastrointestinal function in both human and animal models, potential links between an impaired microbiota imbalance and the psycho-immunopathophysiology of irritable bowel syndrome, and the results of the available clinical trials to date.
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Affiliation(s)
- Cristina Almansa
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Jacksonville, FL, USA
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Li SG, Wang JY, Luo F. Adult-age inflammatory pain experience enhances long-term pain vigilance in rats. PLoS One 2012; 7:e36767. [PMID: 22574223 PMCID: PMC3344941 DOI: 10.1371/journal.pone.0036767] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Accepted: 04/12/2012] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent pain-related behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. METHODOLOGY/PRINCIPAL FINDINGS In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. CONCLUSIONS/SIGNIFICANCE These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight the importance of treatment of chronic pain at an early stage.
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Affiliation(s)
- Sheng-Guang Li
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- The Graduate University, Chinese Academy of Sciences, Beijing, China
| | - Jin-Yan Wang
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Fei Luo
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
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The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol 2012; 46:220-7. [PMID: 22157240 DOI: 10.1097/mcg.0b013e31823712b1] [Citation(s) in RCA: 165] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The clinical effect of probiotics on irritable bowel syndrome (IBS) is still controversial. AIMS We aimed to evaluate the effects of a probiotic mixture on IBS symptoms and the composition of fecal microbiota in patients with diarrhea-dominant IBS (D-IBS). METHODS Fifty patients with D-IBS were randomized into placebo or probiotic mixture (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, and Streptococcus thermophilus 1.0×10 CFU) groups. Treatment was taken daily for 8 weeks. The primary outcome was adequate relief (AR) of overall IBS symptoms, which was assessed weekly for 10 weeks. A responder was defined as a patient who experienced AR for at least half of the 10-week study period. Secondary outcomes included the effects on individual symptoms, stool parameters, and IBS quality of life. The fecal flora compositions were analyzed by polymerase chain reaction denaturing gradient gel electrophoresis (DGGE). RESULTS The proportion of AR was consistently higher in the probiotics group than in the placebo group throughout the 10-week period (P<0.05). The proportion of responders was significantly higher in the probiotics group than in the placebo group (48% vs. 12%, P=0.01). Stool consistency improved significantly in the probiotics group compared with the placebo group. Percent changes in individual symptom scores were similar in the 2 groups, but IBS quality of life improvement tended to be higher in the probiotics group. Comparison of denaturing gradient gel electrophoresis profiles of fecal flora showed that the concordance rate between bacterial compositions before and after treatment was significantly higher in the probiotics group than in the placebo group (69.5% vs. 56.5%, P=0.005). CONCLUSIONS The probiotic mixture was effective in providing AR of overall IBS symptoms and improvement of stool consistency in D-IBS patients, although it had no significant effect on individual symptoms. The therapeutic effect of probiotics is associated with the stabilization of intestinal microbiota.
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Larsson MBO, Tillisch K, Craig A(B, Engström M, Labus J, Naliboff B, Lundberg P, Ström M, Mayer EA, Walter SA. Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome. Gastroenterology 2012; 142:463-472.e3. [PMID: 22108191 PMCID: PMC3288538 DOI: 10.1053/j.gastro.2011.11.022] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2011] [Revised: 10/31/2011] [Accepted: 11/02/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences. METHODS We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest. RESULTS The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls. CONCLUSIONS Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.
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Affiliation(s)
- MBO Larsson
- Department of Clinical and Experimental Medicine/Gastroenterology, Center for Medical Image Science and Visualization (CMIV), Linköping University; Department of Gastroenterology, UHL, County Council of Östergötland, Linköping, Sweden
| | - K Tillisch
- Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive, Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, USA
| | - A.D. (Bud) Craig
- Barrow Neurological Institute, Phoenix, AZ, USA; Visiting Professor at the Department of Clinical and Experimental Medicine, Linköping University, Sweden
| | - M Engström
- Department of Medical and Health Sciences (IMH)/Radiology, Linköping University, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Sweden
| | - J Labus
- Oppenheimer Family Center for Neurobiology of Stress, Department of Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, USA
| | - B Naliboff
- Oppenheimer Family Center for Neurobiology of Stress, Department of Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, USA
| | - P Lundberg
- Center for Medical Image Science and Visualization, CMIV; Radiation Physics, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University; Department of Radiation Physics UHL, County Council of Östergötland, Linköping, Sweden; Center for Medical Image Science and Visualization, CMIV; Radiology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University; Department of Radiology UHL, County Council of Östergötland, Linköping, Sweden
| | - M Ström
- Department of Clinical and Experimental Medicine/Gastroenterology, Linköping University; Department of Gastroenterology, UHL, County Council of Östergötland, Linköping, Sweden
| | - EA Mayer
- Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, USA
| | - SA Walter
- Department of Clinical and Experimental Medicine/Gastroenterology, Center for Medical Image Science and Visualization (CMIV), Linköping University; Department of Gastroenterology, UHL, County Council of Östergötland, Linköping, Sweden
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Plasma hormones facilitated the hypermotility of the colon in a chronic stress rat model. PLoS One 2012; 7:e31774. [PMID: 22363728 PMCID: PMC3282740 DOI: 10.1371/journal.pone.0031774] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2011] [Accepted: 01/18/2012] [Indexed: 01/12/2023] Open
Abstract
Objective To study the relationship between brain-gut peptides, gastrointestinal hormones and altered motility in a rat model of repetitive water avoidance stress (WAS), which mimics the irritable bowel syndrome (IBS). Methods Male Wistar rats were submitted daily to 1-h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay Kits. Proximal colonic smooth muscle (PCSM) contractions were studied in an organ bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca were recorded by the patch-clamp technique. Results The number of fecal pellets during 1 h of acute restraint stress and the plasma hormones levels of substance P (SP), thyrotropin-releasing hormone (TRH), motilin (MTL), and cholecystokinin (CCK) in WAS rats were significantly increased compared with SWAS rats, whereas vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and corticotropin releasing hormone (CRH) in WAS rats were not significantly changed and peptide YY (PYY) in WAS rats was significantly decreased. Likewise, the amplitudes of spontaneous contractions of PCSM in WAS rats were significantly increased comparing with SWAS rats. The plasma of WAS rats (100 µl) decreased the amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs were significantly decreased in WAS rats compared with SWAS rats and the plasma of WAS rats (100 µl) increased the amplitude of IKv and IBKCa in normal rats. Conclusion These results suggest that WAS leads to changes of plasma hormones levels and to disordered myogenic colonic motility in the short term, but that the colon rapidly establishes a new equilibrium to maintain the normal baseline functioning.
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Liebregts T, Adam B, Bertel A, Lackner C, Neumann J, Talley NJ, Gerken G, Holtmann G. Psychological stress and the severity of post-inflammatory visceral hyperalgesia. Eur J Pain 2012; 11:216-22. [PMID: 16545971 DOI: 10.1016/j.ejpain.2006.02.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2005] [Revised: 01/27/2006] [Accepted: 02/06/2006] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Lowered visceral sensory thresholds are a key finding in at least a subgroup of patients with functional bowel disorders. Stress and inflammation contribute to this altered visceral sensory function. We aimed to elucidate the role of repetitive stress and acute mucosal inflammation, alone and in combination, on sensory function. METHODS In randomized order, trinitrobenzenesulfonic acid (TNBS) plus the equal amount of ethanol or saline were instilled into the colorectum of female Lewis rats. Colorectal distensions (CRD) were performed with a barostat device (3 min/40 mmHg); to quantify the visceromotor response (VMR) to CRD, electromyographic activity (EMG) of the abdominal muscles was recorded. In randomized order, equal numbers of both treatment groups underwent either seven days (1 h/day) repetitive water avoidance stress (WAS) or sham WAS. CRD's were conducted 28 days later. Colonic tissue samples were obtained to characterize inflammation and blood samples were taken at day 28 to measure plasma IL-2 levels by enzyme-linked immunosorbent assay (ELISA). RESULTS Compared to controls (662+/-114 microV) TNBS (1081+/-227 microV), WAS (1366+/-125 microV) and the combination of both (1477+/-390 microV) significantly augmented the VMR to CRD. TNBS and/or WAS caused significant inflammatory changes at day 5, while only TNBS+WAS also showed signs of mucosal inflammation on day 14 and significantly elevated IL-2 levels on day 28. CONCLUSIONS Stress and inflammation cause long lasting alterations of visceral sensory function. Concomitant stress further increases post-inflammatory visceral hyperalgesia.
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Affiliation(s)
- Tobias Liebregts
- Royal Adelaide Hospital, Department of Gastroenterology, Hepatology and General Medicine, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia
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Kennedy PJ, Clarke G, Quigley EMM, Groeger JA, Dinan TG, Cryan JF. Gut memories: towards a cognitive neurobiology of irritable bowel syndrome. Neurosci Biobehav Rev 2012; 36:310-40. [PMID: 21777613 DOI: 10.1016/j.neubiorev.2011.07.001] [Citation(s) in RCA: 135] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2011] [Revised: 06/30/2011] [Accepted: 07/04/2011] [Indexed: 01/06/2023]
Abstract
The brain and the gut are engaged in continual crosstalk along a number of pathways collectively termed the 'brain-gut axis'. Over recent years it has become increasingly clear that dysregulation of the axis at a number of levels can result in disorders such as irritable bowel syndrome (IBS). With recent advances in neuroimaging technologies, insights into the neurobiology of IBS are beginning to emerge. However the cognitive neurobiology of IBS has remained relatively unexplored to date. In this review we summarise the available data on cognitive function in IBS. Moreover, we specifically address three key pathophysiological factors, namely; stress, immune activation and chronic pain, together with other factors involved in the manifestation of IBS, and explore how each of these components may impact centrally, what neurobiological mechanisms might be involved, and consider the implications for cognitive functioning in IBS. We conclude that each factor addressed could significantly impinge on central nervous system function, supporting the view that future research efforts must be directed towards a detailed assessment of cognitive function in IBS.
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Affiliation(s)
- Paul J Kennedy
- Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
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Barbara G, Cremon C, De Giorgio R, Dothel G, Zecchi L, Bellacosa L, Carini G, Stanghellini V, Corinaldesi R. Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome. Curr Gastroenterol Rep 2011; 13:308-15. [PMID: 21537962 DOI: 10.1007/s11894-011-0195-7] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Visceral hypersensitivity is currently considered a key pathophysiological mechanism involved in pain perception in large subgroups of patients with functional gastrointestinal disorders, including irritable bowel syndrome (IBS). In IBS, visceral hypersensitivity has been described in 20%-90% of patients. The contribution of the central nervous system and psychological factors to visceral hypersensitivity in patients with IBS may be significant, although still debated. Peripheral factors have gained increasing attention following the recognition that infectious enteritis may trigger the development of persistent IBS symptoms, and the identification of mucosal immune, neural, endocrine, microbiological, and intestinal permeability abnormalities. Growing evidence suggests that these factors play an important role in pain transmission from the periphery to the brain via sensory nerve pathways in large subsets of patients with IBS. In this review, we will report on recent data on mechanisms involved in visceral hypersensitivity in IBS, with particular attention paid to peripheral mechanisms.
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Affiliation(s)
- Giovanni Barbara
- Department of Clinical Medicine and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy.
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Gaylord SA, Palsson OS, Garland EL, Faurot KR, Coble RS, Mann JD, Frey W, Leniek K, Whitehead WE. Mindfulness training reduces the severity of irritable bowel syndrome in women: results of a randomized controlled trial. Am J Gastroenterol 2011; 106:1678-88. [PMID: 21691341 PMCID: PMC6502251 DOI: 10.1038/ajg.2011.184] [Citation(s) in RCA: 171] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES This prospective, randomized controlled trial explored the feasibility and efficacy of a group program of mindfulness training, a cognitive-behavioral technique, for women with irritable bowel syndrome (IBS). The technique involves training in intentionally attending to present-moment experience and non-judgmental awareness of body sensations and emotions. METHODS Seventy-five female IBS patients were randomly assigned to eight weekly and one half-day intensive sessions of either mindfulness group (MG) training or a support group (SG). Participants completed the IBS severity scale (primary outcome), IBS-quality of life, brief symptom inventory-18, visceral sensitivity index, treatment credibility scale, and five-facet mindfulness questionnaire before and after treatment and at 3-month follow-up. RESULTS Women in the MG showed greater reductions in IBS symptom severity immediately after training (26.4% vs. 6.2% reduction; P=0.006) and at 3-month follow-up (38.2% vs. 11.8%; P=0.001) relative to SG. Changes in quality of life, psychological distress, and visceral anxiety were not significantly different between groups immediately after treatment, but evidenced significantly greater improvements in the MG than in the SG at the 3-month follow-up. Mindfulness scores increased significantly more in the MG after treatment, confirming effective learning of mindfulness skills. Participants' ratings of the credibility of their assigned interventions, measured after the first group session, were not different between groups. CONCLUSIONS This randomized controlled trial demonstrated that mindfulness training has a substantial therapeutic effect on bowel symptom severity, improves health-related quality of life, and reduces distress. The beneficial effects persist for at least 3 months after group training.
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Affiliation(s)
- Susan A. Gaylord
- Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Olafur S. Palsson
- Department of Medicine, Center for Functional Gastrointestinal and Motility Disorders and Division of Gastroenterology and Hepatology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Eric L. Garland
- College of Social Work, Florida State University, Tallahassee, Florida, USA
| | - Keturah R. Faurot
- Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Rebecca S. Coble
- Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - J. Douglas Mann
- Department of Neurology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - William Frey
- Training and Development, Offi ce of Human Resources, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Karyn Leniek
- Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - William E. Whitehead
- Department of Medicine, Center for Functional Gastrointestinal and Motility Disorders and Division of Gastroenterology and Hepatology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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