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Choudhary A, Fikree A, Ruffle JK, Takahashi K, Palsson OS, Aziz I, Aziz Q. A machine learning approach to stratify patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders according to disorders of gut brain interaction, comorbidities and quality of life. Neurogastroenterol Motil 2025; 37:e14957. [PMID: 39543811 DOI: 10.1111/nmo.14957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 10/06/2024] [Accepted: 10/21/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND A high prevalence of disorders of gut-brain interaction (DGBI) exist in patients with hypermobile Ehlers-Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD). However, it is unknown if clusters of hEDS/HSD patients exist which overlap with different DGBIs and whether this overlap influences presence of comorbidities and quality of life. We aimed to study these knowledge gaps. METHODS A prospectively collected hEDS/HSD cohort of 1044 individuals were studied. We undertook Uniform Manifold Approximation and Projection-enabled (UMAP) dimension reduction to create a representation of nonlinear interactions between hEDS/HSD and DGBIs, from which individuals were stratified into clusters. Somatization, Postural Tachycardia Syndrome (PoTS), autonomic symptoms, psychological factors and quality of life were statistically compared between clusters. KEY RESULTS The mean age of patients was 40 ± 13.2 years; 87.8% were female. Patients segregated into three clusters: Cluster 0 (n = 466): hEDS/HSD+ functional foregut disorders (FFD) + irritable bowel syndrome (IBS); Cluster 1 (n = 180): hEDS/HSD+ IBS and Cluster 2 (n = 337): hEDS/HSD alone. In cluster 0, we demonstrated increased somatization (p <0.0001), anxiety (p <0.0001), depression (p <0.0001), PoTS prevalence (p = 0.003), autonomic symptoms (p <0.0001) and reduced quality of life (p <0.0001) compared to cluster 2. Cluster 0 had greater comorbidity burden than cluster 1. CONCLUSIONS Within hEDS/HSD, subgroups exist with a high prevalence of FFD and IBS. These subgroups have a higher prevalence of psychological disorders, dysautonomia and poorer quality of life compared with hEDS/HSD alone. Further research should focus on healthcare utilization, management and prognosis in hEDS/HSD and DGBI overlap.
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Affiliation(s)
- Anisa Choudhary
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Asma Fikree
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - James K Ruffle
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- High Dimensional Neurology Group, UCL Queen Square Institute of Neurology, University College London, London, UK
| | - Kazuya Takahashi
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Olafur S Palsson
- Centre for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals and University of Sheffield, Sheffield, UK
| | - Qasim Aziz
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Rajindrajith S, Boey CCM, Devanarayana NM, Niriella MA, Thapar N, Benninga MA. Navigating through 65 years of insights: lessons learned on functional abdominal pain in children. Eur J Pediatr 2024:10.1007/s00431-024-05667-4. [PMID: 38972964 DOI: 10.1007/s00431-024-05667-4] [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: 03/21/2024] [Revised: 06/21/2024] [Accepted: 06/24/2024] [Indexed: 07/09/2024]
Abstract
In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.
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Affiliation(s)
- Shaman Rajindrajith
- Department of Pediatrics, Faculty of Medicine, University of Colombo, Colombo 8, 00800, Western Province, Sri Lanka.
| | - Christopher Chiong-Meng Boey
- Department of Paediatrics, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
- Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lampur, Malaysia
| | | | | | - Nikhil Thapar
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - Marc Alexander Benninga
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Wade U, Pascual-Figal DA, Rabbani F, Ernst M, Albert A, Janssens I, Dierckxsens Y, Iqtadar S, Khokhar NA, Kanwal A, Khan A. The Possible Synergistic Pharmacological Effect of an Oral Berberine (BBR) and Curcumin (CUR) Complementary Therapy Alleviates Symptoms of Irritable Bowel Syndrome (IBS): Results from a Real-Life, Routine Clinical Practice Settings-Based Study. Nutrients 2024; 16:1204. [PMID: 38674895 PMCID: PMC11053504 DOI: 10.3390/nu16081204] [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: 03/12/2024] [Revised: 04/11/2024] [Accepted: 04/14/2024] [Indexed: 04/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder, characterised by recurrent abdominal discomfort and altered bowel movements. IBS cause a significantly negative impact on quality of life (QoL). Growing pharmacological evidence suggests that berberine (BBR) and curcumin (CUR) may mitigate IBS symptoms through multiple complementary synergistic mechanisms, resulting in the attenuation of intestinal inflammation and regulation of bowel motility and gut functions. In the present observational study conducted under real-life routine clinical practice settings, 146 patients diagnosed with IBS were enrolled by general practitioner clinics and pharmacies in Belgium. For the first time, this study assessed the potential synergistic pharmacological effect of a combined oral BBR/CUR supplement (Enterofytol® PLUS, containing 200 mg BBR and 49 mg CUR) (two tablets daily for 2 months), serving as complementary therapy in the management of IBS. Following the 2-month supplementation, significant improvements were observed in the patients' IBS severity index (IBSSI) (47.5%) and all the primary IBS symptoms, such as abdominal discomfort (47.2%), distension (48.0%), intestinal transit (46.8%), and QoL (48.1%) (all p < 0.0001). The improvement in the patients' IBSSI was independent of age, sex, and IBS sub-types. The patients' weekly maximum stool passage frequency decreased significantly (p < 0.0001), and the stool status normalized (p < 0.0001). The patients' need for concomitant conventional IBS treatment decreased notably: antispasmodics by 64.0% and antidiarrhoeals by 64.6%. Minor adverse effects were reported by a small proportion (7.1%) of patients, mostly gastrointestinal. The majority (93.1%) experienced symptom improvement or resolution, with a high satisfaction rate (82.6%) and willingness to continue the supplementation (79.0%). These findings support the potential synergistic pharmacological role of BBR and CUR in IBS, and their co-supplementation may alleviate IBS symptoms and improve QoL.
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Affiliation(s)
- Ursula Wade
- Department of Basic and Clinical Neuroscience, Kings College London, London SE5 9RT, UK;
| | - Domingo A. Pascual-Figal
- Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, 30120 Murcia, Spain;
| | - Fazale Rabbani
- Lady Reading Hospital, Peshawar 25000, Pakistan; (F.R.); (A.K.)
| | - Marie Ernst
- Biostatistics and Research Methods Center (B-STAT), CHU of Liège and University of Liège, 4000 Liège, Belgium (A.A.)
| | - Adelin Albert
- Biostatistics and Research Methods Center (B-STAT), CHU of Liège and University of Liège, 4000 Liège, Belgium (A.A.)
| | | | | | - Somia Iqtadar
- Department of Medicine, King Edward Medical University, Lahore 54000, Pakistan;
| | - Nisar A. Khokhar
- Department of Medicine, Bilawal Medical College, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan;
| | - Ayesha Kanwal
- Lady Reading Hospital, Peshawar 25000, Pakistan; (F.R.); (A.K.)
| | - Amjad Khan
- Department of Biochemistry, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan
- Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
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Wang L, Luo X, Qing X, Fang S, Jiang T, Wang Q, Zhong Z, Yang Y, Yang J, Song G, Su X, Wei W. Symptom effects and central mechanism of acupuncture in patients with functional gastrointestinal disorders: a systematic review based on fMRI studies. BMC Gastroenterol 2024; 24:47. [PMID: 38267863 PMCID: PMC10809475 DOI: 10.1186/s12876-024-03124-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 01/02/2024] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. AIM To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. METHODS PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. RESULTS Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. CONCLUSION Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary.
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Affiliation(s)
- Lin Wang
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Xiaoying Luo
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xiangli Qing
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
- Graduate School of Chengdu University of Chinese Medicine, Chengdu, China
| | - Shuangshuang Fang
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Tianyuan Jiang
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Qianying Wang
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Zhuotai Zhong
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Yang Yang
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Jianqin Yang
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Gengqing Song
- Department of Gastroenterology and Hepatology, MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH, USA
| | - Xiaolan Su
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China
| | - Wei Wei
- Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, City, Beijing, China.
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Rodrigues JM, Ventura C, Abreu M, Santos C, Monte J, Machado JP, Santos RV. Electro-Acupuncture Effects Measured by Functional Magnetic Resonance Imaging-A Systematic Review of Randomized Clinical Trials. Healthcare (Basel) 2023; 12:2. [PMID: 38200908 PMCID: PMC10778902 DOI: 10.3390/healthcare12010002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/07/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024] Open
Abstract
INTRODUCTION Electro-acupuncture, an innovative adaptation of traditional acupuncture, combines electrical stimulation with acupuncture needles to enhance therapeutic effects. While acupuncture is widely used, its biological mechanisms remain incompletely understood. Recent research has explored the neurophysiological aspects of acupuncture, particularly through functional magnetic resonance imaging (fMRI) to investigate its effects on brain activity. METHODS In this systematic review, we conducted an extensive search for randomized clinical trials examining electro-acupuncture effects measured by fMRI. We employed strict eligibility criteria, quality assessment, and data extraction. RESULTS Five studies met our inclusion criteria and were analyzed. The selected studies investigated electro-acupuncture in various medical conditions, including carpal tunnel syndrome, fibromyalgia, Crohn's disease, irritable bowel syndrome, and obesity. Notably, electro-acupuncture was found to modulate brain activity and connectivity in regions associated with pain perception, emotional regulation, and cognitive processing. These findings align with the holistic approach of traditional Chinese medicine, emphasizing the interconnectedness of body and mind. DISCUSSION In carpal tunnel syndrome, electro-acupuncture at both local and distal sites showed neurophysiological improvements, suggesting distinct neuroplasticity mechanisms. In fibromyalgia, somatosensory electro-acupuncture correlated with reduced pain severity, enhanced brain connectivity, and increased gamma-aminobutyric acid levels. For Crohn's disease, electro-acupuncture influenced the homeostatic afferent processing network, potentially mitigating gut inflammation. Electro-acupuncture for irritable bowel syndrome led to decreased activity in the anterior cingulate cortex, offering pain relief, while electro-acupuncture for obesity impacted brain regions associated with dietary inhibition and emotional regulation. CONCLUSION This systematic review provides evidence that electro-acupuncture can positively impact a range of medical conditions, possibly by modulating brain activity and connectivity. While the quality of the reviewed studies is generally good, further research with larger sample sizes and longer-term assessments is needed to better understand the mechanisms and optimize electro-acupuncture protocols for specific health conditions. The limited number of studies in this review emphasizes the need for broader investigations in this promising field. The research protocol was registered in PROSPERO (CRD42023465866).
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Affiliation(s)
- Jorge Magalhães Rodrigues
- IPTC—Research Department in Complementary Therapies, Portuguese Institute of Taiji and Qigong, 4470-765 Maia, Portugal
- ABS—Health Level Department, Atlântico Business School, 4405-604 Vila Nova de Gaia, Portugal
- CBSin—Center of BioSciences in Integrative Health, 4200-135 Porto, Portugal
- ICBAS—School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Cristina Ventura
- IPTC—Research Department in Complementary Therapies, Portuguese Institute of Taiji and Qigong, 4470-765 Maia, Portugal
- ABS—Health Level Department, Atlântico Business School, 4405-604 Vila Nova de Gaia, Portugal
| | - Manuela Abreu
- IPTC—Research Department in Complementary Therapies, Portuguese Institute of Taiji and Qigong, 4470-765 Maia, Portugal
- ABS—Health Level Department, Atlântico Business School, 4405-604 Vila Nova de Gaia, Portugal
| | - Catarina Santos
- IPTC—Research Department in Complementary Therapies, Portuguese Institute of Taiji and Qigong, 4470-765 Maia, Portugal
- ABS—Health Level Department, Atlântico Business School, 4405-604 Vila Nova de Gaia, Portugal
| | - Joana Monte
- ABS—Health Level Department, Atlântico Business School, 4405-604 Vila Nova de Gaia, Portugal
| | - Jorge Pereira Machado
- CBSin—Center of BioSciences in Integrative Health, 4200-135 Porto, Portugal
- ICBAS—School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
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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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Aberrant Spontaneous Brain Activity in Coronary Heart Disease Using Fractional Amplitude of Low-Frequency Fluctuations: A Preliminary Resting-State Functional MRI Study. DISEASE MARKERS 2022; 2022:2501886. [PMID: 35692880 PMCID: PMC9187430 DOI: 10.1155/2022/2501886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/14/2022] [Accepted: 05/17/2022] [Indexed: 11/18/2022]
Abstract
Objective This study is aimed at exploring the spontaneous brain activity changes by measuring the fractional amplitude of low-frequency fluctuations (fALFF) and their relationship with clinical characteristics in patients with coronary heart disease (CHD). Methods Coronary heart disease patients (n = 25) and age, gender, and education level-matched control subjects (controls, n = 35) were included. The grey matter volume (GMV) and fALFF values were calculated to assess the difference in brain structure and function between the two groups, respectively. Correlation analyses between the fALFF values and clinical characteristics were further assessed in CHD patients. In addition, receiver operating characteristic (ROC) curves were conducted to access the diagnostic ability of the fALFF method. Results There was no significant difference in GMV between the CHD and control groups. Compared with the control group, patients with CHD showed significantly decreased fALFF in the left precentral/postcentral gyrus and increased fALFF in the right inferior cerebellum. Patients with a history of myocardial infarction (MI) showed significantly decreased fALFF values of the right inferior cerebellum than patients without MI. There was no significant correlation between the fALFF values in specific brain regions and disease duration. Furthermore, the ROC curves of abnormal brain regions showed the perfect accuracy of the fALFF value in distinguishing between CHD patients and controls. Conclusion CHD demonstrated aberrant neural activity in specific brain regions mainly related to sensorimotor networks and pain processing, which may contribute to understanding the underlying neurological mechanism of CHD.
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Su C, Liu W, Wang Q, Qiu S, Li M, Lv Y, Yu Y, Jia X, Li H. Abnormal resting-state local spontaneous functional activity in irritable bowel syndrome patients: A meta-analysis. J Affect Disord 2022; 302:177-184. [PMID: 35066011 DOI: 10.1016/j.jad.2022.01.075] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/01/2022] [Accepted: 01/18/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The current understanding of the pathogenesis underlying IBS is still unclear. Numerous studies have reported local abnormal resting state spontaneous functional activity in IBS patients in widespread brain regions. However, the results have not yet yielded consistent conclusions. Thus, we investigated common spontaneous functional activity abnormalities in patients with IBS by conducting a voxel-based meta-analysis. METHODS Up to December 2021, we performed a systematic search of IBS studies in five databases. These studies investigated the differences of resting state spontaneous brain activity between patients with IBS and healthy controls (HCs). The reference lists of included studies, relevant reviews and meta-analyses were investigated manually. Anisotropic effect-size signed differential mapping (AES-SDM) was applied in this meta-analysis. RESULTS Twelve studies encompassing 335 patients with IBS and 327 HCs were included in this meta-analysis. The local brain activities of the left calcarine fissure and surrounding cortex, right postcentral gyrus, left postcentral gyrus, left cerebellum, left inferior temporal gyrus, and left inferior frontal gyrus of triangular part in IBS patients were significantly increased compared with HCs, while the brain activities of the left anterior cingulate and paracingulate gyrus, right middle frontal gyrus, right supramarginal gyrus, left middle frontal gyrus, left precuneus, right putamen and right insula were significantly decreased compared with HCs. CONCLUSION The current study expands on a growing literature exploring resting state activity in IBS, which provides useful insights for understanding the underlying pathophysiology of nonorganic functional bowel disease and developing more targeted treatment and intervention strategies.
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Affiliation(s)
- Chang Su
- College of Teacher Education, Zhejiang Normal University, Jinhua, China; Key Laboratory of Intelligent Education Technology and Application, Zhejiang Normal University, Jinhua, China
| | - Wanlun Liu
- College of Teacher Education, Zhejiang Normal University, Jinhua, China
| | - Qianqian Wang
- College of Teacher Education, Zhejiang Normal University, Jinhua, China
| | - Shasha Qiu
- College of Teacher Education, Zhejiang Normal University, Jinhua, China; Key Laboratory of Intelligent Education Technology and Application, Zhejiang Normal University, Jinhua, China
| | - Mengting Li
- College of Teacher Education, Zhejiang Normal University, Jinhua, China
| | - Yating Lv
- Institute of Brain Science and Department of Psychology, School of Education, Hangzhou Normal University, Hangzhou, China; Center for Cognition and Brain Disorders, the Affiliated Hospital, Hangzhou Normal University, Hangzhou, China
| | - Yang Yu
- Department of Psychiatry, Second Affiliated Hospital, College of Medicine, Zhejiang University, China
| | - Xize Jia
- College of Teacher Education, Zhejiang Normal University, Jinhua, China.
| | - Huayun Li
- College of Teacher Education, Zhejiang Normal University, Jinhua, China; Key Laboratory of Intelligent Education Technology and Application, Zhejiang Normal University, Jinhua, China.
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Li J, Wang C, Li Z, Fu B, Han Q, Ye M. Abnormalities of intrinsic brain activity in irritable bowel syndrome (IBS): A protocol for systematic review and meta analysis of resting-state functional imaging. Medicine (Baltimore) 2021; 100:e25883. [PMID: 34032700 PMCID: PMC8154468 DOI: 10.1097/md.0000000000025883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 04/21/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders affecting up to 11.5% of the general global population. The brain-gut axis has been shown to play an important role in the pathogenesis of IBS. Several studies confirmed that intrinsic brain abnormalities existed in patients with IBS. But, studies of abnormal regional homogeneity (ReHo) in IBS have reported inconsistent results. The objective of this protocol is to conduct a meta-analysis using the Seed-based d mapping software package to identify the most consistent and replicable findings of ReHo in IBS patients. METHOD We will search the following three electronic databases: MEDLINE, EMBASE and Web of Science. The primary outcome will include the peak coordinates and effect sizes of differences in ReHo between patients with IBS and healthy controls from each dataset. The secondary outcomes will be the effects of age, illness severity, illness duration, and scanner field strength. The SDM approach was used to conduct voxel-wise meta-analysis. Whole-brain voxel-based jackknife sensitivity analysis was performed to conduct jackknife sensitivity analysis. A random effects model with Q statistics is used to conduct heterogeneity and publication bias between studies and meta-regression analyses were carried out to examine the effects of age, illness severity, illness duration, and scanner field strength. RESULTS The results of this paper will be submitted to a peer-reviewed journal for publication. CONCLUSION This research will determine the consistent pattern of alterations in ReHo in IBS patients.
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Affiliation(s)
- J. Li
- Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei
- College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine/Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan, China
| | - C. Wang
- Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei
| | - Z.M. Li
- Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei
| | - B. Fu
- Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei
| | - Q. Han
- Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei
| | - M. Ye
- Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei
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10
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Masciullo L, Viscardi MF, Piacenti I, Scaramuzzino S, Cavalli A, Piccioni MG, Porpora MG. A deep insight into pelvic pain and endometriosis: a review of the literature from pathophysiology to clinical expressions. Minerva Obstet Gynecol 2021; 73:511-522. [PMID: 33904687 DOI: 10.23736/s2724-606x.21.04779-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Endometriosis is a chronic inflammatory disease that affects approximately 10% of women of reproductive age. Its clinical manifestations are highly heterogeneous, but pelvic pain is the most frequent, causing functional disability. Cyclic or acyclic chronic pelvic pain (CPP), dysmenorrhea and dyspareunia are frequent symptoms which often compromise all aspects of the women's quality of life (QoL). The pathophysiology of endometriosis-related pain is extremely complex and not always clear. The aim of this literature review is to focus on recent updates on the clinical presentation, the pathophysiology and the most important mechanisms involved in the pathogenesis of pelvic pain in endometriosis. A literature search in the Cochrane library, PubMed, Scopus and web of Science databases has been performed, identifying articles from January 1995 to November 2020. Several processes seem to be involved in the pathogenesis of pain, but many aspects are still unclear. Scientific evidence has shown that a correlation between pain severity and stage of endometriosis rarely occurs, whereas there is a significant correlation between pain and the presence of deep endometriosis. Onset and intensity of pain may be due to a complex process involving central sensitization and peripheral activation of nociceptive pathways as well as dysfunction of the immune system and of the hypothalamic-pituitary-adrenal (HPA) axis. A deeper understanding of these different pathogenetic mechanisms may improve future treatments in women with painful endometriosis.
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Affiliation(s)
- Luisa Masciullo
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Maria F Viscardi
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Ilaria Piacenti
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Sara Scaramuzzino
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Alessandra Cavalli
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Maria G Piccioni
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Maria G Porpora
- Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy -
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11
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Murphy LK, de la Vega R, Kohut SA, Kawamura JS, Levy RL, Palermo TM. Systematic Review: Psychosocial Correlates of Pain in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:697-710. [PMID: 32458966 DOI: 10.1093/ibd/izaa115] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Pain is a common symptom in pediatric inflammatory bowel disease (IBD) and is associated with poor health outcomes, yet additional knowledge about the psychosocial correlates of pain is needed to optimize clinical care. The purpose of this study is to systematically review the psychosocial factors associated with pain and pain impact in youth diagnosed with IBD within a developmentally informed framework. METHODS Manual and electronic searches yielded 2641 references. Two authors conducted screening (98% agreement), and data extraction was performed in duplicate. Average study quality was rated using the National Institutes of Health Quality Assessment Tool. RESULTS Ten studies (N = 763 patients; N = 563 Crohn disease, N = 200 ulcerative/ indeterminate colitis) met the inclusion criteria. Findings showed consistent evidence that higher levels of child depression symptoms and child pain catastrophizing were associated with significantly greater pain and pain impact (magnitude of association ranged from small to large across studies). Greater pain and pain impact were also associated with higher levels of child anxiety symptoms, child pain threat, child pain worry, and parent pain catastrophizing. Within the included studies, female sex and disease severity were both significantly associated with pain and pain impact. Study quality was moderate on average. CONCLUSIONS There is evidence that child psychosocial factors are associated with pain and pain impact in pediatric IBD; more studies are needed to examine parent- and family-level psychosocial factors. Youth with IBD should be routinely screened for pain severity, pain impact, and psychosocial risk factors such as anxiety/depression.
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Affiliation(s)
- Lexa K Murphy
- Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Rocio de la Vega
- Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, Washington, USA
| | - Sara Ahola Kohut
- Department of Psychology and Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Joy S Kawamura
- Department of Psychiatry and Behavioral Medicine, Seattle Children's Hospital, Seattle, Washington, USA.,Department of Psychiatry, University of Washington, Seattle, Washington, USA
| | - Rona L Levy
- Department of Social Work, University of Washington, Seattle, Washington, USA
| | - Tonya M Palermo
- Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, Washington, USA.,Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, USA
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12
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Kamiya T, Osaga S, Kubota E, Fukudo S, Motoya S, Murakami K, Nagahara A, Shiotani A, Sugimoto M, Suzuki H, Watanabe T, Yamaguchi S, Chan FKL, Hahm KB, Fock KM, Zhu Q. Questionnaire-Based Survey on Epidemiology of Functional Gastrointestinal Disorders and Current Status of Gastrointestinal Motility Testing in Asian Countries. Digestion 2020; 102:73-89. [PMID: 33326975 DOI: 10.1159/000513292] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 11/24/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate the present situation of epidemiology and diagnostic tests of FGID in clinical practice in some East and Southeast Asian countries. METHODS The questionnaire focusing on current situation of FGID diagnosis and gastrointestinal motility testing was distributed to members of the International Gastroenterology Consensus Symposium study group and collected to be analyzed. RESULTS The prevalence rates of subtypes of both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are relatively similar in all Asian countries. In these countries, most patients underwent both upper endoscopy and Helicobacter pylori test to diagnose FD. Colonoscopy was also frequently performed to diagnose IBS and chronic constipation. The frequency of gastrointestinal motility testing to examine gastric emptying and colonic transit time varied among Asian countries. CONCLUSIONS This survey revealed epidemiology of FGIDs and current status of gastrointestinal motility testing in some East and Southeast Asian countries.
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Affiliation(s)
- Takeshi Kamiya
- Department of Medical Innovation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan,
| | - Satoshi Osaga
- Department of Medical Innovation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Eiji Kubota
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shin Fukudo
- Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Satoshi Motoya
- IBD Center, Sapporo Kosei General Hospital, Sapporo, Japan
| | | | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akiko Shiotani
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital and Hepatology, Tokyo, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Satoru Yamaguchi
- First Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Francis K L Chan
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Ki-Baik Hahm
- Digestive Disease Center, CHA University School of Medicine and CHA University Bundang Medical Center, Seoul, Republic of Korea
| | - Kwong Ming Fock
- Department of Gastroenterology, Changi General Hospital, Singapore, Singapore, Singapore
| | - Qi Zhu
- SinoUnited Health, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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13
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Wang T, Yan YF, Yang L, Huang YZ, Duan XH, Su KH, Liu WL. Effects of Zuojin pill on depressive behavior and gastrointestinal function in rats with chronic unpredictable mild stress: Role of the brain-gut axis. JOURNAL OF ETHNOPHARMACOLOGY 2020; 254:112713. [PMID: 32109545 DOI: 10.1016/j.jep.2020.112713] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 12/27/2019] [Accepted: 02/22/2020] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1β, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1β, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .
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Affiliation(s)
- Tao Wang
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, PR China
| | - Yan-Feng Yan
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, 210014, PR China
| | - Lu Yang
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, 210014, PR China
| | - Yu-Zhen Huang
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, 210014, PR China
| | - Xin-Hui Duan
- Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Kun-Han Su
- Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Wan-Li Liu
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, 210014, PR China.
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14
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Gastrointestinal disorders-induced pain. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2019.100580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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15
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Zein SA, Karakatsanis NA, Issa M, Haj‐Ali AA, Nehmeh SA. Physical performance of a long axial field‐of‐view PET scanner prototype with sparse rings configuration: A Monte Carlo simulation study. Med Phys 2020; 47:1949-1957. [DOI: 10.1002/mp.14046] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/26/2019] [Accepted: 01/11/2020] [Indexed: 01/22/2023] Open
Affiliation(s)
- Sara A. Zein
- Department of Radiology Weill Cornell Medical College New York NY 10021USA
| | | | - Mohammad Issa
- School of Engineering Lebanese International University Beirut Lebanon
| | - Amin A. Haj‐Ali
- School of Engineering Lebanese International University Beirut Lebanon
| | - Sadek A. Nehmeh
- Department of Radiology Weill Cornell Medical College New York NY 10021USA
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16
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Murphy LK, Rights JD, Ricciuto A, Church PC, Ahola Kohut S. Biopsychosocial Correlates of Presence and Intensity of Pain in Adolescents With Inflammatory Bowel Disease. Front Pediatr 2020; 8:559. [PMID: 33014942 PMCID: PMC7506075 DOI: 10.3389/fped.2020.00559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 07/31/2020] [Indexed: 12/11/2022] Open
Abstract
Background: There is growing consensus that pain in pediatric inflammatory bowel disease (IBD) is not fully explained by disease-related processes. However, previous studies have largely measured individual biological, psychological, or social risk factors for pain in isolation. Further, not all youth with IBD presenting to clinic will report presence of pain, and those who do vary in their reports of pain intensity. This study therefore extends prior research by determining biopsychosocial correlates of both presence and intensity of pain in adolescents with IBD, in order to inform targeted pain management intervention approaches. Methods: Adolescents with IBD followed at SickKids, Toronto, and their parents were consecutively enrolled from outpatient clinic. IBD characteristics (diagnosis, time since diagnosis, patient-reported disease activity) were collected. Adolescents reported on current pain (NRS-10), internalizing symptoms (Strengths and Difficulties Questionnaire), and pain catastrophizing (Pain Catastrophizing Scale-Child). Parents reported on protective responses to child pain (Adult Responses to Child Pain) and pain catastrophizing (Pain Catastrophizing Scale-Child). Hurdle models were conducted to examine predictors of presence and intensity of pain in the same model. Biological (patient-reported disease activity, IBD diagnosis subtype, illness duration), psychological (internalizing symptoms, pain catastrophizing), and social (parent pain catastrophizing, parent protective responses) factors were entered as predictors, adjusting for age and sex. Results: Participants included 100 adolescents (12-18; Mean = 15 years) with IBD (60% Crohn's Disease, 40% Ulcerative Colitis or IBD-unclassified) and 76 parents. The majority of the sample was in clinical remission or reported minimal symptoms. Half of participants reported no current pain; for those reporting pain, intensity ranged 1-7 (M = 3.43, SD = 1.98). Disease activity (OR = 53.91, p < 0.001) and adolescent internalizing symptoms (OR = 7.62, p = 0.03) were significant predictors of presence of pain. Disease activity (RR = 1.37, p = 0.03) and parent protective responses (RR = 1.45, p = 0.02) were significant predictors of intensity of pain. Conclusions: Results suggest that the experience of pain in pediatric IBD is biopsychosocially determined. Patient-reported disease activity and internalizing symptoms predicted presence of pain, while disease activity and parent protective responses predicted intensity of pain. While medical intervention in pediatric IBD is focused on disease management, results suggest that depression/anxiety symptoms as well as parent protective responses may be important targets of pain management interventions in pediatric IBD.
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Affiliation(s)
- Lexa K Murphy
- Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, United States
| | - Jason D Rights
- Department of Psychology, University of British Columbia, Vancouver, BC, United States
| | - Amanda Ricciuto
- Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.,SickKids Research Institute, Toronto, ON, Canada.,Department of Paediatrics, University of Toronto, Toronto, ON, Canada
| | - Peter C Church
- Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.,Department of Paediatrics, University of Toronto, Toronto, ON, Canada
| | - Sara Ahola Kohut
- Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.,SickKids Research Institute, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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17
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Pushkina AV, Avalueva AB, Bakulin IG, Topanova AA, Murzina AA, Sitkin SI, Lapinsky IV, Skazyvaeva EV. Functional polymorphism of the serotonin reuptake transporter SLC6A4 gene in various clinical variants of irritable bowel syndrome. ALMANAC OF CLINICAL MEDICINE 2019; 47:496-504. [DOI: 10.18786/2072-0505-2019-47-072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Rationale:Irritable bowel syndrome (IBS) is a multifactorial disease, the genetic aspect of which is being actively studied.Aim:To investigate functional polymorphism of the serotonin reuptake transporter (SERT)SLC6A4gene of various clinical variants of IBS.Materials and methods:We performed a cross-sectional single center study in 79 Caucasian patients with IBS (according to the Rome criteria IV). The patients were divided into two groups: group 1, IBS with diarrhea (IBS-D, n = 45) and group 2, IBS with constipation (IBS-C, n = 34). The control group included 59 Caucasian patients with gastrointestinal disorders without IBS. Polymorphism5-HTTLPRof theSLC6A4gene was assessed in all subjects. In group 1 patients, blood serotonin levels were measured and psychological tests were performed, including Spielberger's State / Trait Anxiety Inventory, quality of life by SF36 and GSRS, Asthenia scale, VAS scores for pain intensity.Results:Thirty-five of 45 (77.8%) patients with IBS-D carried the mutantSallele, which was significantly more frequent than in the IBS-C group (p = 0.002) and in the control group (p = 0.005). There were no statistically significant differences (p = 0.54) in the frequency of detection of the homozygousLLgenotype (normal allele) and the heteroand homozygous mutant alleles (SLandSS) genotype between the IBS-C and control patients. In the IBS-D group, a gender difference for the mutantSSallele of5-HTTLPRwas found, with significantly higher frequency in female patients (p = 0.0147). No significant gender differences in the genotype distribution between the patients with IBS-C and the control group were found. There were also no differences in blood serotonin levels in the IBS patients with various5-HTTLPRtypes (p = 0.086); they were all in the reference range. However, there was a trend towards lower serotonin levels in theLLgenotype carriers compared to those with theSS/SLpolymorphisms. The Gastroenterological inventoryGSRSdemonstrated significantly higher total score for the constipation syndrome in the patients with homozygousLL 5-HTTLPRpolymorphism, compared to that in the patients with theSS/SLgenotype (p = 0.013).Conclusion:The results may be related to lower expression of theSLC6A4gene in the carriers of the mutant allele in the5-HTTLPRpromoter and subsequent decreased rate of serotonin uptake, with resulting stimulation of the gastrointestinal tract. TheSERTpolymorphism of theSLC6A4gene is worth further investigation as a potential candidate gene in the IBS pathophysiology.
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Affiliation(s)
- A. V. Pushkina
- North-Western State Medical University named after I.I. Mechnikov
| | - A. B. Avalueva
- North-Western State Medical University named after I.I. Mechnikov
| | - I. G. Bakulin
- North-Western State Medical University named after I.I. Mechnikov
| | | | - A. A. Murzina
- North-Western State Medical University named after I.I. Mechnikov
| | - S. I. Sitkin
- North-Western State Medical University named after I.I. Mechnikov; Almazov National Medical Research Centre; State Research Institute of Highly Pure Biopreparations
| | - I. V. Lapinsky
- North-Western State Medical University named after I.I. Mechnikov
| | - E. V. Skazyvaeva
- North-Western State Medical University named after I.I. Mechnikov
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18
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The Dietary Management of Patients with Irritable Bowel Syndrome: A Narrative Review of the Existing and Emerging Evidence. Nutrients 2019; 11:nu11092162. [PMID: 31505870 PMCID: PMC6770052 DOI: 10.3390/nu11092162] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/29/2019] [Accepted: 09/04/2019] [Indexed: 12/21/2022] Open
Abstract
Even though irritable bowel syndrome (IBS) has been known for more than 150 years, it still remains one of the research challenges of the 21st century. According to the current diagnostic Rome IV criteria, IBS is characterized by abdominal pain associated with defecation and/or a change in bowel habit, in the absence of detectable organic causes. Symptoms interfere with the daily life of patients, reduce health-related quality of life and lower the work productivity. Despite the high prevalence of approximately 10%, its pathophysiology is only partly understood and seems multifactorial. However, many patients report symptoms to be meal-related and certain ingested foods may generate an exaggerated gastrointestinal response. Patients tend to avoid and even exclude certain food products to relieve their symptoms, which could affect nutritional quality. We performed a narrative paper review of the existing and emerging evidence regarding dietary management of IBS patients, with the aim to enhance our understanding of how to move towards an individualized dietary approach for IBS patients in the near future.
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19
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Mayer EA, Labus J, Aziz Q, Tracey I, Kilpatrick L, Elsenbruch S, Schweinhardt P, Van Oudenhove L, Borsook D. Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report. Gut 2019; 68:1701-1715. [PMID: 31175206 PMCID: PMC6999847 DOI: 10.1136/gutjnl-2019-318308] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/18/2019] [Accepted: 03/24/2019] [Indexed: 12/12/2022]
Abstract
Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
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Affiliation(s)
- Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Jennifer Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Qasim Aziz
- Neurogastroenterology Group, Queen Mary University of London, London, UK
| | - Irene Tracey
- Departments of Anaesthetics and Clinical Neurology, Pembroke College, Oxford, UK
| | - Lisa Kilpatrick
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Sigrid Elsenbruch
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg, Duisburg, Germany
| | | | - Lukas Van Oudenhove
- Translational Research in GastroIntestinal Disorders, KU Leuven Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium
| | - David Borsook
- Center for Pain and the Brain, Boston Children's, Massachusetts General and McLean Hospitals, Harvard Medical School, Boston, Massachusetts, USA
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Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: What does the future hold? World J Gastroenterol 2019; 25:552-566. [PMID: 30774271 PMCID: PMC6371005 DOI: 10.3748/wjg.v25.i5.552] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 12/19/2018] [Accepted: 12/28/2018] [Indexed: 02/06/2023] Open
Abstract
Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.
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Affiliation(s)
- Kashif Mukhtar
- Centre of Excellence in Women and Child Health, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Hasham Nawaz
- Department of Medicine, Section of Gastroenterology, Aga Khan University, Karachi, Sindh 74800, Pakistan
| | - Shahab Abid
- Department of Medicine, Section of Gastroenterology, Aga Khan University, Karachi, Sindh 74800, Pakistan
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Pietrzak A, Skrzydło-Radomańska B, Mulak A, Lipiński M, Małecka-Panas E, Reguła J, Rydzewska G. Guidelines on the management of irritable bowel syndrome: In memory of Professor Witold Bartnik. PRZEGLAD GASTROENTEROLOGICZNY 2018; 13:259-288. [PMID: 30581501 PMCID: PMC6300851 DOI: 10.5114/pg.2018.78343] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 09/09/2018] [Indexed: 12/15/2022]
Abstract
These guidelines constitute an update of the previous "Recommendations on the management of irritable bowel syndrome" issued in 2008. They have been developed by a Task Force organized by the Governing Board of the Polish Society of Gastroenterology. They discuss, with particular emphasis on new scientific data covering papers published since 2008, the aetiology, epidemiology, clinical presentation, diagnostic principles and criteria for the diagnosis, and recommendations for the treatment of irritable bowel syndrome (IBS). The English-language acronym for the syndrome (IBS) has become popular in medical and popular scientific language. It is also widely recognized by patients who identify with this diagnosis. Therefore, in the discussed guidelines, this is what we will use.
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Affiliation(s)
- Anna Pietrzak
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | | | - Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Michał Lipiński
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior, Warsaw, Poland
| | - Ewa Małecka-Panas
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Jarosław Reguła
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Grażyna Rydzewska
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior, Warsaw, Poland
- Department of the Prevention of Alimentary Tract Diseases, Faculty of Medicine and Health Science, Jan Kochanowski University, Kielce, Poland
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Wiley JW, Chang L. Functional Bowel Disorders. Gastroenterology 2018; 155:1-4. [PMID: 29454798 DOI: 10.1053/j.gastro.2018.02.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 01/31/2018] [Accepted: 02/02/2018] [Indexed: 12/15/2022]
Affiliation(s)
- John W Wiley
- Department Internal Medicine, University of Michigan, Ann Arbor, Michigan.
| | - Lin Chang
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Vatche and Tamar Manoukian Division of Gastroenterology, University of California, Los Angeles, Los Angeles, California
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Li DY, Dai YK, Zhang YZ, Huang MX, Li RL, Ou-yang J, Chen WJ, Hu L. Systematic review and meta-analysis of traditional Chinese medicine in the treatment of constipation-predominant irritable bowel syndrome. PLoS One 2017; 12:e0189491. [PMID: 29253850 PMCID: PMC5734785 DOI: 10.1371/journal.pone.0189491] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Accepted: 11/27/2017] [Indexed: 12/15/2022] Open
Abstract
AIM This meta-analysis analyzed the efficacy and safety of traditional Chinese medicine (TCM) for the treatment of irritable bowel syndrome with constipation (IBS-C). METHODS We searched seven electronic databases for randomized controlled trials investigating the efficacy of TCM in the treatment of IBS-C. The search period was from inception to June 1, 2017. Eligible RCTs compared TCM with cisapride and mosapride. Article quality was evaluated with the Cochrane Risk Bias Tool in the Cochrane Handbook by two independent reviewers. Begg's test was performed to evaluate publication bias. Review Manager 5.3 and Stata 12.0 were used for analyses. RESULTS Eleven eligible studies comprising a total of 906 participants were identified. In the primary outcome, TCM showed significant improvement in overall clinical efficacy compared with cisapride and mosapride (odds ratio [OR] = 4.00; 95% confidence interval [CI]: 2.74,5.84; P < 0.00001). In terms of secondary outcomes, TCM significantly alleviated abdominal pain (OR = 5.69; 95% CI: 2.35, 13.78; P = 0.0001), defecation frequency (OR = 4.38; 95% CI: 1.93, 9.93. P = 0.0004), and stool form (OR = 4.96; 95% CI: 2.11, 11.65; P = 0.0002) in the treatment group as compared to the control group. A lower recurrence rate was associated with TCM as compared to cisapride and mosapride (OR = 0.15; 95% CI: 0.08, 0.27; P < 0.00001). No adverse effects were observed during TCM treatment. CONCLUSIONS TCM showed greater improvement in terms of clinical efficacy in the treatment of IBS-C than cisapride and mosapride, although it was not possible to draw a definitive conclusion due to the small sample size, high risk, and low quality of the studies. Large multi-center and long-term high-quality randomized control trials are needed.
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Affiliation(s)
- Dan-yan Li
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Yun-kai Dai
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Yun-zhan Zhang
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Meng-xin Huang
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ru-liu Li
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Jia Ou-yang
- Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wei-jing Chen
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ling Hu
- Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- * E-mail:
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Ellingsen DM, Garcia RG, Lee J, Lin RL, Kim J, Thurler AH, Castel S, Dimisko L, Rosen BR, Hadjikhani N, Kuo B, Napadow V. Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults. Neurogastroenterol Motil 2017; 29:10.1111/nmo.13004. [PMID: 27910222 PMCID: PMC5423835 DOI: 10.1111/nmo.13004] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 11/07/2016] [Indexed: 02/03/2023]
Abstract
Cyclic Vomiting Syndrome (CVS) has been linked to episodic migraine, yet little is known about the precise brain-based mechanisms underpinning CVS, and whether these associated conditions share similar pathophysiology. We investigated the functional integrity of salience (SLN) and sensorimotor (SMN) intrinsic connectivity networks in CVS, migraine and healthy controls using brain functional Magnetic Resonance Imaging. CVS, relative to both migraine and controls, showed increased SLN connectivity to middle/posterior insula, a key brain region for nausea and viscerosensory processing. In contrast, this same region showed diminished SMN connectivity in both CVS and migraine. These results highlight both unique and potentially shared pathophysiology between these conditions, and suggest a potential target for therapeutics in future studies.
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Affiliation(s)
- Dan-Mikael Ellingsen
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Psychology, University of Oslo, Oslo, Norway
| | - Ronald G. Garcia
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Neuroscience Group, School of Medicine, Universidad de Santander (UDES), Bucaramanga, Colombia
- Connors Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Jeungchan Lee
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Richard L. Lin
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jieun Kim
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Korean Institute for Oriental Medicine, Daejeon, Korea
| | - Andrea H Thurler
- Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Shahar Castel
- Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Laurie Dimisko
- Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Bruce R. Rosen
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Nouchine Hadjikhani
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Braden Kuo
- Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Vitaly Napadow
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Törnblom H, Drossman DA. Centrally Targeted Pharmacotherapy for Chronic Abdominal Pain: Understanding and Management. Handb Exp Pharmacol 2017; 239:417-440. [PMID: 28204956 DOI: 10.1007/164_2016_106] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Chronic abdominal pain has a widespread impact on the individual and the society. Identifying and explaining mechanisms of importance for the pain experience within a biopsychosocial context are central in order to select treatment that has a chance for symptom reduction. With current knowledge of brain-gut interactions, chronic abdominal pain, which mostly appears in functional gastrointestinal disorders, to a large extent involves pain mechanisms residing within the brain. As such, the use of centrally targeted pharmacotherapy as an effective treatment option is obvious in a selected number of patients. The antidepressants are most common, but also other classes of medications can be used, either alone or in combination. The latter option refers to when there is insufficient effect of one drug alone or side effects limiting dosage, and when combined in lower doses, certain drugs give rise to augmentation effects. This chapter outlines basic mechanisms of importance for the understanding of chronic abdominal pain and the pharmacologic treatment options.
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Affiliation(s)
- Hans Törnblom
- Dept of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345, Gothenburg, Sweden.
| | - Douglas A Drossman
- Drossman Center for the Education and Practice of Biopsychosocial Care, Professor Emeritus of Medicine and Psychiatry, UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Drossman Gastroenterology PLLC, Chapel Hill, NC, USA
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An integrative review of methylation at the serotonin transporter gene and its dialogue with environmental risk factors, psychopathology and 5-HTTLPR. Neurosci Biobehav Rev 2016; 72:190-209. [PMID: 27880876 DOI: 10.1016/j.neubiorev.2016.11.011] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 11/04/2016] [Accepted: 11/06/2016] [Indexed: 11/24/2022]
Abstract
Gene-environment (G×E) interactions have largely been regarded as the root of many complex disorders, including several psychiatric disorders. In this regard, it has been hypothesized that epigenetic mechanisms may be the main mediators of such interactions. Of particular interest is the previously described interaction between psychosocial stress and genetic variability of the serotonin transporter gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature concerning SLC6A4 methylation in association with environmental, clinical or genetic variables. While SLC6A4 hypermethylation has typically been described to be independently associated with both early life stress and depressive disorders, only a few papers address whether methylation could mediate the interaction between stress and 5-HTTLPR in predicting psychopathological risk. Nevertheless, research preliminarily indicates a methylation-driven increased vulnerability of carriers of the short allele of 5-HTTLPR to psychiatric disorders when exposed to early stress or soon after exposure to stress.
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27
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Kennedy PJ, Murphy AB, Cryan JF, Ross PR, Dinan TG, Stanton C. Microbiome in brain function and mental health. Trends Food Sci Technol 2016. [DOI: 10.1016/j.tifs.2016.05.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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28
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Lei WY, Chang CY, Wu JH, Lin FH, Hsu Chen C, Chang CF, Lin YR, Wu HP. An Initial Attack of Urinary Stone Disease Is Associated with an Increased Risk of Developing New-Onset Irritable Bowel Syndrome: Nationwide Population-Based Study. PLoS One 2016; 11:e0157701. [PMID: 27337114 PMCID: PMC4919104 DOI: 10.1371/journal.pone.0157701] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Accepted: 04/19/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The neurotransmitter pathways in irritable bowel syndrome (IBS) and urinary stone attacks are both related to serotonin, and each disease may be influenced by viscero-visceral hyperalgesia. However, the relationship between urinary tract stone disease and IBS has never been addressed. We aimed to investigate the risk of suffering new-onset IBS after an initial urinary stone attack using a nationwide database. METHODS A study group enrolled a total of 13,254 patients who were diagnosed with an initial urinary stone attack; a comparison group recruited 39,762 matched non-urinary stone participants during 2003 and 2007. We followed each patient for 3 years to determine new-onset IBS. We also used Cox proportional hazards models to analyze the risk of IBS between the study and comparison groups after modified by demographics, residence, patient characteristics and personal histories. RESULTS The occurrence rates of IBS were 3.3% (n = 440) and 2.6% (n = 1,034) respectively in the study and comparison groups. A covariate-adjusted hazard ratio (HR) of IBS in the study group that was 1.28 times greater (HR = 1.29, 95% CI, 1.15-1.44) than that in the comparison group was showed in the stratified Cox proportional analysis. The adjusted HRs of IBS did not decrease after considering demographics and past histories. The majority of IBS (30.5%) occurred within the first 6 months after the stone attack. CONCLUSION Patients with an initial urinary stone attack are at increased risk of developing new-onset IBS. The HRs of IBS did not decrease even after adjusting for patient demographics and past histories. Most importantly, 30.5% of IBS occurred within the first 6 months after the urinary stone attack.
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Affiliation(s)
- Wei-Yuan Lei
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chih-Yu Chang
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
- Department of Biological Science and Technology of Biochemical Engineering, National Chiao Tung University, Hsinchu, Taiwan
| | - Jr-Hau Wu
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Fei-Hung Lin
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng Hsu Chen
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chin-Fu Chang
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yan-Ren Lin
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Han-Ping Wu
- Division of Pediatric General Medicine, Department of Pediatrics, Chang Gung Memorial Hospital at Linko, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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29
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Weaver KR, Sherwin LB, Walitt B, Melkus GD, Henderson WA. Neuroimaging the brain-gut axis in patients with irritable bowel syndrome. World J Gastrointest Pharmacol Ther 2016; 7:320-333. [PMID: 27158548 PMCID: PMC4848255 DOI: 10.4292/wjgpt.v7.i2.320] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Revised: 10/06/2015] [Accepted: 02/24/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome (IBS).
METHODS: A database search for relevant literature was conducted using PubMed, Scopus and Embase in February 2015. Date filters were applied from the year 2009 and onward, and studies were limited to those written in the English language and those performed upon human subjects. The initial search yielded 797 articles, out of which 38 were pulled for full text review and 27 were included for study analysis. Investigations were reviewed to determine study design, methodology and results, and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.
RESULTS: Analysis of study data resulted in the abstraction of four key themes: Neurohormonal differences, anatomic measurements of brain structure and connectivity, differences in functional responsiveness of the brain during rectal distention, and confounding/correlating patient factors. Studies in this review noted alterations of glutamate in the left hippocampus (HIPP), commonalities across IBS subjects in terms of brain oscillation patterns, cortical thickness/gray matter volume differences, and neuroanatomical regions with increased activation in patients with IBS: Anterior cingulate cortex, mid cingulate cortex, amygdala, anterior insula, posterior insula and prefrontal cortex. A striking finding among interventions was the substantial influence that patient variables (e.g., sex, psychological and disease related factors) had upon the identification of neuroanatomical differences in structure and connectivity.
CONCLUSION: The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.
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Boeckxstaens G, Camilleri M, Sifrim D, Houghton LA, Elsenbruch S, Lindberg G, Azpiroz F, Parkman HP. Fundamentals of Neurogastroenterology: Physiology/Motility - Sensation. Gastroenterology 2016; 150:S0016-5085(16)00221-3. [PMID: 27144619 DOI: 10.1053/j.gastro.2016.02.030] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 02/09/2016] [Indexed: 12/14/2022]
Abstract
The fundamental gastrointestinal functions include motility, sensation, absorption, secretion, digestion and intestinal barrier function. Digestion of food and absorption of nutrients normally occurs without conscious perception. Symptoms of functional gastrointestinal disorders are often triggered by meal intake suggesting abnormalities in the physiological processes are involved in the generation of symptoms. In this manuscript, normal physiology and pathophysiology of gastrointestinal function, and the processes underlying symptom generation are critically reviewed. The functions of each anatomical region of the digestive tract are summarized. The pathophysiology of perception, motility, mucosal barrier, and secretion in functional gastrointestinal disorders as well as effects of food, meal intake and microbiota on gastrointestinal motility and sensation are discussed. Genetic mechanisms associated with visceral pain and motor functions in health and functional gastrointestinal disorders are reviewed. Understanding the basis for digestive tract functions is essential to understand dysfunctions in the functional gastrointestinal disorders.
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Affiliation(s)
- Guy Boeckxstaens
- Department of Gastroenterology, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, KU Leuven, Leuven, Belgium
| | | | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Bart's and the London School of Medicine, Queen Mary, University of London, London, UK
| | - Lesley A Houghton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Greger Lindberg
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Fernando Azpiroz
- Digestive Diseases Department, University Hospital Vall D'Hebron, Autonomous University of Barcelona, Barcelona, Spain
| | - Henry P Parkman
- Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
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31
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Liu X, Silverman A, Kern M, Ward BD, Li SJ, Shaker R, Sood MR. Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report. Neurogastroenterol Motil 2016; 28:43-53. [PMID: 26467966 PMCID: PMC4688218 DOI: 10.1111/nmo.12695] [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: 05/04/2015] [Accepted: 08/31/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (i) brain responses to visceral stimulation in adolescents are similar to those in adults, and (ii) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models. METHODS Irritable bowel syndrome patients and controls received subliminal and liminal rectal distension during imaging. Stimulus-induced brain activations were determined. Salience network integrity was evaluated by the functional connectivity of its seed regions activated by rectal distension in the insular and cingulate cortices. KEY RESULTS Compared with controls, IBS patients demonstrated greater activation to rectal distension in neural structures of the homeostatic afferent and emotional arousal networks, especially the anterior cingulate and insular cortices. Greater brain responses to liminal vs subliminal distension were observed in both groups. Particularly, IBS is uniquely associated with an excessive coupling of the salience network with the DMN and ECN in their key frontal and parietal node areas. CONCLUSIONS & INFERENCES Our study provided consistent evidence supporting the theoretical predictions of altered salience network functioning as a neuropathological mechanism of IBS symptoms.
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Affiliation(s)
- Xiaolin Liu
- Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alan Silverman
- Division of Pediatric Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mark Kern
- Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - B. Douglas Ward
- Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Shi-Jiang Li
- Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Reza Shaker
- Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Manu R. Sood
- Division of Pediatric Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, USA
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Ke J, Qi R, Liu C, Xu Q, Wang F, Zhang L, Lu G. Abnormal regional homogeneity in patients with irritable bowel syndrome: A resting-state functional MRI study. Neurogastroenterol Motil 2015; 27:1796-803. [PMID: 26403620 DOI: 10.1111/nmo.12692] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 08/26/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Task-related brain imaging research has implicated abnormal central processing of visceral sensation in irritable bowel syndrome (IBS). However, how brain function of IBS patients is altered during resting-state remains to be determined. We investigated spontaneous brain activity of patients with IBS using regional homogeneity (ReHo) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). METHODS Thirty-one patients with diarrhea-predominant IBS and 32 age- and sex- matched healthy controls underwent clinical assessments and rs-fMRI scanning. ReHo maps were acquired by calculating the Kendall's coefficient of concordance and compared between the IBS group and the control group. The effects of psychological disturbance on group differences were assessed by including anxiety and depression levels as covariates in the statistical analyses. Multiple regression analyses were conducted to examine the relationship between ReHo values and disease duration, symptom severity, and pain intensity. KEY RESULTS Compared with controls, IBS patients showed increased ReHo in the postcentral gyrus and thalamus and decreased ReHo in the anterior cingulate cortex and prefrontal cortex. The inclusion of anxiety and depression as covariates did not alter ReHo differences between the two groups. Furthermore, significant correlations were found between clinical indices and ReHo values in some brain regions in the IBS group. CONCLUSIONS & INFERENCES IBS patients have abnormal local synchronization of spontaneous brain activity in regions involved in visceral afferent processing, emotional arousal, and cognitive modulation. Combining rs-fMRI and ReHo analysis seems to be a valuable approach to investigate the neural basis of IBS.
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Affiliation(s)
- J Ke
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - R Qi
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - C Liu
- Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Q Xu
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - F Wang
- Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - L Zhang
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - G Lu
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
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Abstract
Chronic visceral pain syndromes are important clinical problems with largely unmet medical needs. Based on the common overlap with other chronic disorders of visceral or somatic pain, mood and affect, and their responsiveness to centrally targeted treatments, an important role of central nervous system in their pathophysiology is likely. A growing number of brain imaging studies in irritable bowel syndrome, functional dyspepsia, and bladder pain syndrome/interstitial cystitis has identified abnormalities in evoked brain responses, resting state activity, and connectivity, as well as in gray and white matter properties. Structural and functional alterations in brain regions of the salience, emotional arousal, and sensorimotor networks, as well as in prefrontal regions, are the most consistently reported findings. Some of these changes show moderate correlations with behavioral and clinical measures. Most recently, data-driven machine-learning approaches to larger data sets have been able to classify visceral pain syndromes from healthy control subjects. Future studies need to identify the mechanisms underlying the altered brain signatures of chronic visceral pain and identify targets for therapeutic interventions.
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Benson S, Rebernik L, Wegner A, Kleine-Borgmann J, Engler H, Schlamann M, Forsting M, Schedlowski M, Elsenbruch S. Neural circuitry mediating inflammation-induced central pain amplification in human experimental endotoxemia. Brain Behav Immun 2015; 48:222-31. [PMID: 25882910 DOI: 10.1016/j.bbi.2015.03.017] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 03/26/2015] [Accepted: 03/27/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND & AIMS To elucidate the brain mechanisms underlying inflammation-induced visceral hyperalgesia in humans, in this functional magnetic resonance imaging (fMRI) study we tested if intravenous administration of lipopolysaccharide (LPS) involves altered central processing of visceral pain stimuli. METHODS In this randomized, double-blind, placebo-controlled fMRI study, 26 healthy male subjects received either an intravenous injection of low-dose LPS (N=14, 0.4 ng/kg body weight) or placebo (N=12, control group). Plasma cytokines (TNF-α, IL-6), body temperature, plasma cortisol and mood were assessed at baseline and up to 6 h post-injection. At baseline and 2 h post-injection (test), rectal pain thresholds and painful rectal distension-induced blood oxygen level-dependent (BOLD) responses in brain regions-of-interest were assessed. To address specificity for visceral pain, BOLD responses to non-painful rectal distensions and painful somatic stimuli (i.e., punctuate mechanical stimulation) were also analyzed as control stimuli. RESULTS Compared to the control group, LPS-treated subjects demonstrated significant and transient increases in TNF-α, IL-6, body temperature and cortisol, along with impaired mood. In response to LPS, rectal pain thresholds decreased in trend, along with enhanced up-regulation of rectal pain-induced BOLD responses within the posterior insula, dorsolateral prefrontal (DLPFC), anterior midcingulate (aMCC) and somatosensory cortices (all FWE-corrected p<0.05). Within the LPS group, more pronounced cytokine responses correlated significantly with enhanced rectal pain-induced neural activation in DLPFC and aMCC. No significant LPS effects were observed on neural responses to non-painful rectal distensions or mechanical stimulation. CONCLUSIONS These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain.
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Affiliation(s)
- Sven Benson
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Laura Rebernik
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany; Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Alexander Wegner
- Clinic for Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Julian Kleine-Borgmann
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Harald Engler
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Marc Schlamann
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Michael Forsting
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Manfred Schedlowski
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
| | - Sigrid Elsenbruch
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany.
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Nan J, Liu J, Mu J, Zhang Y, Zhang M, Tian J, Liang F, Zeng F. Anatomically related gray and white matter alterations in the brains of functional dyspepsia patients. Neurogastroenterol Motil 2015; 27:856-64. [PMID: 25825020 DOI: 10.1111/nmo.12560] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Accepted: 03/03/2015] [Indexed: 12/24/2022]
Abstract
BACKGROUND Previous studies summarized altered brain functional patterns in functional dyspepsia (FD) patients, but how the brain structural patterns are related to FD remains largely unclear. The objective of this study was to determine the brain structural characteristics in FD patients. METHODS Optimized voxel-based morphometry and tract-based spatial statistics were employed to investigate the changes in gray matter (GM) and white matter (WM) respectively in 34 FD patients with postprandial distress syndrome and 33 healthy controls based on T1-weighted and diffusion-weighted imaging. The Pearson's correlation evaluated the link among GM alterations, WM abnormalities, and clinical variables in FD patients. The optimal brain structural parameters for identifying FD were explored using the receiver operating characteristic curve. KEY RESULTS Compared to controls, FD patients exhibited a decrease in GM density (GMD) in the right posterior insula/temporal superior cortex (marked as pINS), right inferior frontal cortex (IFC), and left middle cingulate cortex, and an increase in fractional anisotropy (FA) in the posterior limb of the internal capsule, posterior thalamic radiation, and external capsule (EC). Interestingly, the GMD in the pINS was significantly associated with GMD in the IFC and FA in the EC. Moreover, the EC adjacent to the pINS provided the best performance for distinguishing FD patients from controls. CONCLUSIONS & INFERENCES Our results showed pINS-related structural abnormalities in FD patients, indicating that GM and WM parameters were not affected independently. These findings would lay the foundation for probing an efficient target in the brain for treating FD.
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Affiliation(s)
- J Nan
- School of Life Science and Technology, Xidian University, Xi'an, China
| | - J Liu
- School of Life Science and Technology, Xidian University, Xi'an, China
| | - J Mu
- School of Life Science and Technology, Xidian University, Xi'an, China
| | - Y Zhang
- School of Life Science and Technology, Xidian University, Xi'an, China
| | - M Zhang
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - J Tian
- School of Life Science and Technology, Xidian University, Xi'an, China
| | - F Liang
- The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - F Zeng
- The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Li MJ, Niu JK, Miao YL. Relationship between brain-gut axis and inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2015; 23:1097-1103. [DOI: 10.11569/wcjd.v23.i7.1097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing inflammatory disease affecting the gastrointestinal tract. The incidence of IBD has increased dramatically year by year in China. Currently, the IBD research is focused on genetically predisposed factors, immune response, environmental triggers and infections. However, the etiology of IBD is still unclear. Recently, more attention has been paid to the research of neural regulation affecting the progression of IBD. Previous research has revealed that psycho-neuro-endocrine-immune modulation through the brain-gut axis plays a crucial role in the pathogenesis of IBD. It is important to explore other psychotherapies applied to adjutant therapy in IBD. This review reviews the recent advances in understanding the relationship between the brain-gut axis and inflammatory bowel disease.
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Ghoshegir SA, Mazaheri M, Ghannadi A, Feizi A, Babaeian M, Tanhaee M, Karimi M, Adibi P. Pimpinella anisum in the treatment of functional dyspepsia: A double-blind, randomized clinical trial. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2015; 20:13-21. [PMID: 25767516 PMCID: PMC4354059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 07/16/2014] [Accepted: 07/21/2014] [Indexed: 11/18/2022]
Abstract
BACKGROUND We aimed to evaluate the effects of Pimpinella anisum (anise) from Apiaceae family on relieving the symptoms of postprandial distress syndrome (PDS) in this double-blind randomized clinical trial. MATERIALS AND METHODS Totally, 107 patients attending the gastroenterology clinic, aged 18-65 years, diagnosed with PDS according to ROME III criteria and signed a written consent form were enrolled. They were randomized to receive either anise or placebo, blindly, for 4 weeks. Anise group included 47 patients and received anise powders, 3 g after each meal (3 times/day). Control group involved 60 patients and received placebo powders (corn starch), 3 gafter each meal (3 times/day). The severity of Functional dyspepsia (FD) symptoms was assessed by FD severity scale. Assessments were done at baseline and by the end of weeks 2, 4 and 12. Mean scores of severity of FD symptoms and the frequency distribution of patients across the study period were compared. RESULTS The age, sex, body mass index, smoking history, and coffee drinking pattern of the intervention and control groups were not significantly different. Mean (standard deviation) total scores of FD severity scale before intervention in the anise and control groups were 10.6 (4.1) and 10.96 (4.1), respectively (P = 0.6). They were 7.04 (4.1) and 12.30 (4.3) by week 2, respectively (P = 0.0001), 2.44 (4.2) and 13.05 (5.2) by week 4, respectively (P = 0.0001), and 1.08 (3.8) and 13.30 (6.2) by week 12, respectively (P = 0.0001). CONCLUSION This study showed the effectiveness of anise in relieving the symptoms of postpartum depression. The findings were consistent across the study period at weeks 2, 4 and 12.
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Affiliation(s)
- S. Ashraffodin Ghoshegir
- Department of Iranian Traditional Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mazaheri
- Department of Iranian Traditional Medicine, Isfahan University of Medical Sciences, Isfahan, Iran,Address for correspondence: Dr. Mohammad Mazaheri, Department of Iranian Traditional Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. E-mail:
| | - Alireza Ghannadi
- Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahmoud Babaeian
- Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Maryam Tanhaee
- Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrdad Karimi
- Department of Iranian Traditional Medicine School, Tehran University of Medical Science, Tehran, Iran
| | - Peyman Adibi
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis. Pediatr Res 2015; 77:127-35. [PMID: 25303278 DOI: 10.1038/pr.2014.161] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 08/22/2014] [Indexed: 02/08/2023]
Abstract
The conceptual framework for a gut-brain axis has existed for decades. The Human Microbiome Project is responsible for establishing intestinal dysbiosis as a mediator of inflammatory bowel disease, obesity, and neurodevelopmental disorders in adults. Recent advances in metagenomics implicate gut microbiota and diet as key modulators of the bidirectional signaling pathways between the gut and brain that underlie neurodevelopmental and psychiatric disorders in adults. Evidence linking intestinal dysbiosis to neurodevelopmental disease outcomes in preterm infants is emerging. Recent clinical studies show that intestinal dysbiosis precedes late-onset neonatal sepsis and necrotizing enterocolitis in intensive care nurseries. Moreover, strong epidemiologic evidence links late-onset neonatal sepsis and necrotizing enterocolitis in long-term psychomotor disabilities of very-low-birth-weight infants. The notion of the gut-brain axis thereby supports that intestinal microbiota can indirectly harm the brain of preterm infants. In this review, we highlight the anatomy and physiology of the gut-brain axis and describe transmission of stress signals caused by immune-microbial dysfunction in the gut. These messengers initiate neurologic disease in preterm infants. Understanding neural and humoral signaling through the gut-brain axis will offer insight into therapeutic and dietary approaches that may improve the outcomes of very-low-birth-weight infants.
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The brain-gut axis in health and disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2014; 817:135-53. [PMID: 24997032 DOI: 10.1007/978-1-4939-0897-4_6] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The interaction between the brain and the gut has been recognized for many centuries. This bidirectional interaction occurs via neural, immunological and hormonal routes, and is important not only in normal gastrointestinal function but also plays a significant role in shaping higher cognitive function such as our feelings and our subconscious decision-making. Therefore, it remains unsurprising that perturbations in normal signalling have been associated with a multitude of disorders, including inflammatory and functional gastrointestinal disorders, and eating disorders.
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Soares RLS. Irritable bowel syndrome: A clinical review. World J Gastroenterol 2014; 20:12144-12160. [PMID: 25232249 PMCID: PMC4161800 DOI: 10.3748/wjg.v20.i34.12144] [Citation(s) in RCA: 128] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 02/09/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) remains a clinical challenge in the 21st century. It’s the most commonly diagnosed gastrointestinal condition and also the most common reason for referral to gastroenterology clinics. Its can affect up to one in five people at some point in their lives, and has a significantly impact of life quality and health care utilization. The prevalence varies according to country and criteria used to define IBS. Various mechanisms and theories have been proposed about its etiology, but the biopsychosocial model is the most currently accepted for IBS. The complex of symptoms would be the result of the interaction between psychological, behavioral, psychosocial and environmental factors. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria III is the current gold-standard for the diagnoses of IBS. Secure positive evidence of IBS by means of specific disease marker is currently not possible and cannot be currently recommended for routine diagnosis. There is still no clinical evidence to recommend the use of biomarkers in blood to diagnose IBS. However, a number of different changes in IBS patients were demonstrated in recent years, some of which can be used in the future as a diagnostic support. IBS has no definitive treatment but could be controlled by non-pharmacologic management eliminating of some exacerbating factors such certain drugs, stressor conditions and changes in dietary habits.The traditional pharmacologic management of IBS has been symptom based and several drugs have been used. However, the cornerstone of its therapy is a solid patient physician relationship. This review will provide a summary of pathophysiology, diagnostic criteria and current and emerging therapies for IBS.
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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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De Palma G, Collins SM, Bercik P, Verdu EF. The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both? J Physiol 2014; 592:2989-97. [PMID: 24756641 PMCID: PMC4214655 DOI: 10.1113/jphysiol.2014.273995] [Citation(s) in RCA: 206] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 04/17/2014] [Indexed: 12/29/2022] Open
Abstract
The gut-brain axis is the bidirectional communication between the gut and the brain, which occurs through multiple pathways that include hormonal, neural and immune mediators. The signals along this axis can originate in the gut, the brain or both, with the objective of maintaining normal gut function and appropriate behaviour. In recent years, the study of gut microbiota has become one of the most important areas in biomedical research. Attention has focused on the role of gut microbiota in determining normal gut physiology and immunity and, more recently, on its role as modulator of host behaviour ('microbiota-gut-brain axis'). We therefore review the literature on the role of gut microbiota in gut homeostasis and link it with mechanisms that could influence behaviour. We discuss the association of dysbiosis with disease, with particular focus on functional bowel disorders and their relationship to psychological stress. This is of particular interest because exposure to stressors has long been known to increase susceptibility to and severity of gastrointestinal diseases.
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Affiliation(s)
- Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Elena F Verdu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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Muscatello MRA, Bruno A, Scimeca G, Pandolfo G, Zoccali RA. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome. World J Gastroenterol 2014; 20:7570-7586. [PMID: 24976697 PMCID: PMC4069288 DOI: 10.3748/wjg.v20.i24.7570] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 01/18/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.
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Brawn J, Morotti M, Zondervan KT, Becker CM, Vincent K. Central changes associated with chronic pelvic pain and endometriosis. Hum Reprod Update 2014; 20:737-47. [PMID: 24920437 DOI: 10.1093/humupd/dmu025] [Citation(s) in RCA: 171] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Chronic pelvic pain (CPP) is a significant public health problem with 1 million affected women in the UK. Although many pathologies are associated with CPP, the pain experienced is often disproportionate to the extent of disease identified and frequently no pathology is found (chronic pelvic pain syndrome). The central nervous system (CNS) is central to the experience of pain and chronic pain conditions in general are associated with alterations in both the structure and function of the CNS. This review describes the available evidence for central changes in association with conditions presenting with CPP. METHODS A detailed literature search was performed to identify relevant papers, however, this is not a systematic review. RESULTS CPP is associated with central changes similar to those identified in other pain conditions. Specifically these include, alterations in the behavioural and central response to noxious stimulation, changes in brain structure (both increases and decreases in the volume of specific brain regions), altered activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS) and psychological distress. CONCLUSIONS The evidence reviewed in this paper demonstrates that CPP is associated with significant central changes when compared with healthy pain-free women. Moreover, the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions. These findings support the use of adjunctive medication targeting the CNS in these women.
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Affiliation(s)
- Jennifer Brawn
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Matteo Morotti
- Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK Department of Obstetrics and Gynaecology, University of Genoa, Genoa 16100, Italy
| | - Krina T Zondervan
- Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK
| | - Christian M Becker
- Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK
| | - Katy Vincent
- Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK
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De Palma G, Collins SM, Bercik P. The microbiota-gut-brain axis in functional gastrointestinal disorders. Gut Microbes 2014; 5:419-29. [PMID: 24921926 PMCID: PMC4153782 DOI: 10.4161/gmic.29417] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.
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Nan J, Liu J, Zhang D, Yang Y, Yan X, Yin Q, Xiong S, von Deneen KM, Liang F, Gong Q, Qin W, Tian J, Zeng F. Altered intrinsic regional activity and corresponding brain pathways reflect the symptom severity of functional dyspepsia. Neurogastroenterol Motil 2014; 26:660-9. [PMID: 24467632 DOI: 10.1111/nmo.12311] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Accepted: 01/06/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND Increasing evidence shows central abnormalities in functional dyspepsia (FD) patients, but whether the symptom severity is directly reflected in altered brain patterns remains unclear. The purpose of this study was to explore how FD affected the resting functional brain patterns for different degrees of symptom severity. METHODS Functional magnetic resonance imaging was carried out in 40 FD patients and 20 healthy controls. The resting-state brain changes in regional homogeneity (ReHo) and seed correlation analysis were investigated in patients relative to controls. To what degree the brain changes reflected the severity of the disease was assessed by a pattern classification technique. KEY RESULTS Altered ReHo values (p < 0.05, FDR corrected) were discovered in multiple brain areas in FD patients, and only the anterior cingulate cortex (ACC) and thalamus exhibited significant correlation with the severity of dyspepsia symptoms. Compared with controls, the neural signal changes of the thalamus were not found in the less severe FD patient group but in the relatively more severe group, while the ACC showed aberrations in both groups. Seed-based correlation analysis revealed ACC- and thalamus-related functional connectivity differences between FD patients and controls at a voxel-wise level, and the altered thalamic circuits provided the best performance in distinguishing FD patients with different levels of symptom severity. CONCLUSIONS & INFERENCES Our results indicated that the functional abnormalities of the ACC and thalamus may occur at different clinical courses in FD. This may help us better understand the progression of FD.
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Affiliation(s)
- J Nan
- School of Life Science and Technology, Xidian University, Xi'an, China
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Vermeulen W, Man JGD, Pelckmans PA, Winter BYD. Neuroanatomy of lower gastrointestinal pain disorders. World J Gastroenterol 2014; 20:1005-1020. [PMID: 24574773 PMCID: PMC3921524 DOI: 10.3748/wjg.v20.i4.1005] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 11/18/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic abdominal pain accompanying intestinal inflammation emerges from the hyperresponsiveness of neuronal, immune and endocrine signaling pathways within the intestines, the peripheral and the central nervous system. In this article we review how the sensory nerve information from the healthy and the hypersensitive bowel is encoded and conveyed to the brain. The gut milieu is continuously monitored by intrinsic enteric afferents, and an extrinsic nervous network comprising vagal, pelvic and splanchnic afferents. The extrinsic afferents convey gut stimuli to second order neurons within the superficial spinal cord layers. These neurons cross the white commissure and ascend in the anterolateral quadrant and in the ipsilateral dorsal column of the dorsal horn to higher brain centers, mostly subserving regulatory functions. Within the supraspinal regions and the brainstem, pathways descend to modulate the sensory input. Because of this multiple level control, only a small proportion of gut signals actually reaches the level of consciousness to induce sensation or pain. In inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) patients, however, long-term neuroplastic changes have occurred in the brain-gut axis which results in chronic abdominal pain. This sensitization may be driven on the one hand by peripheral mechanisms within the intestinal wall which encompasses an interplay between immunocytes, enterochromaffin cells, resident macrophages, neurons and smooth muscles. On the other hand, neuronal synaptic changes along with increased neurotransmitter release in the spinal cord and brain leads to a state of central wind-up. Also life factors such as but not limited to inflammation and stress contribute to hypersensitivity. All together, the degree to which each of these mechanisms contribute to hypersensitivity in IBD and IBS might be disease- and even patient-dependent. Mapping of sensitization throughout animal and human studies may significantly improve our understanding of sensitization in IBD and IBS. On the long run, this knowledge can be put forward in potential therapeutic targets for abdominal pain in these conditions.
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Napadow V, Lee J, Kim J, Cina S, Maeda Y, Barbieri R, Harris RE, Kettner N, Park K. Brain correlates of phasic autonomic response to acupuncture stimulation: an event-related fMRI study. Hum Brain Mapp 2013; 34:2592-606. [PMID: 22504841 PMCID: PMC3646924 DOI: 10.1002/hbm.22091] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2011] [Revised: 02/01/2012] [Accepted: 03/07/2012] [Indexed: 12/30/2022] Open
Abstract
Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR-) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR- was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR-. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR-, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli.
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Affiliation(s)
- Vitaly Napadow
- Martinos Center for Biomedical ImagingDepartment of RadiologyMassachusetts General HospitalCharlestownMassachusetts
- Department of RadiologyLogan College of ChiropracticChesterfieldMissouri
| | - Jeungchan Lee
- Martinos Center for Biomedical ImagingDepartment of RadiologyMassachusetts General HospitalCharlestownMassachusetts
- Department of Biomedical EngineeringKyung Hee UniversityYonginRepublic of Korea
| | - Jieun Kim
- Martinos Center for Biomedical ImagingDepartment of RadiologyMassachusetts General HospitalCharlestownMassachusetts
| | - Stephen Cina
- Martinos Center for Biomedical ImagingDepartment of RadiologyMassachusetts General HospitalCharlestownMassachusetts
| | - Yumi Maeda
- Martinos Center for Biomedical ImagingDepartment of RadiologyMassachusetts General HospitalCharlestownMassachusetts
- Department of RadiologyLogan College of ChiropracticChesterfieldMissouri
| | - Riccardo Barbieri
- Department of Anesthesia and Critical CareMassachusetts General HospitalBostonMassachusetts
- Department of Brain and Cognitive ScienceMassachusetts Institute of TechnologyCambridgeMassachusetts
| | | | - Norman Kettner
- Department of RadiologyLogan College of ChiropracticChesterfieldMissouri
| | - Kyungmo Park
- Department of Biomedical EngineeringKyung Hee UniversityYonginRepublic of Korea
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Nan J, Liu J, Li G, Xiong S, Yan X, Yin Q, Zeng F, von Deneen KM, Liang F, Gong Q, Qin W, Tian J. Whole-brain functional connectivity identification of functional dyspepsia. PLoS One 2013; 8:e65870. [PMID: 23799056 PMCID: PMC3684590 DOI: 10.1371/journal.pone.0065870] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2013] [Accepted: 04/29/2013] [Indexed: 12/20/2022] Open
Abstract
Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.
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Affiliation(s)
- Jiaofen Nan
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Jixin Liu
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Guoying Li
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Shiwei Xiong
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Xuemei Yan
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Qing Yin
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Fang Zeng
- The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Karen M. von Deneen
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Fanrong Liang
- The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiyong Gong
- Department of Radiology, The Center for Medical Imaging, Huaxi MR Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Wei Qin
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
| | - Jie Tian
- School of Life Sciences and Technology, Xidian University, Xi’an, Peoples R China
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