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Abou Chaaya J, Abou Chaaya J, Jaafar B, Saab L, Abou Chaaya J, Al Ahmar E, Estephan E. Morphological Changes of the Pituitary Gland in Patients with Irritable Bowel Syndrome Using Magnetic Resonance Imaging. J Imaging 2024; 10:226. [PMID: 39330446 PMCID: PMC11433444 DOI: 10.3390/jimaging10090226] [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: 08/13/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a gastrointestinal functional disorder characterized by unclear underlying mechanisms. Several theories propose that hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis leads to elevated cortisol levels and increased sensitivity of gut wall receptors. Given the absence of prior literature on this topic, our study aimed to investigate the potential for diagnosing IBS based on morphological changes in the pituitary gland, specifically its volume and grayscale intensity. Additionally, we aimed to assess whether factors such as gender, age, and body mass index influence these parameters. This retrospective study involved 60 patients, examining the volume and grayscale characteristics of their pituitary glands in the presence of IBS. Our findings revealed a positive correlation between pituitary gland volume and IBS diagnosis, although no significant correlation was observed with grayscale intensity. Due to the limited existing research and the small sample size of our study, further investigation with a larger cohort is warranted to validate these results.
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Affiliation(s)
- Jessica Abou Chaaya
- Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon;
- Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon;
| | - Jennifer Abou Chaaya
- Department of Nutrition and Dietetics, Faculty of Public Health Section 2, Lebanese University, Beirut, Lebanon;
| | - Batoul Jaafar
- Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon;
| | - Lea Saab
- Faculty of Engineering, Sagesse University, Furn El Chebbak, Baabda, Lebanon;
| | - Jad Abou Chaaya
- Lab-STICC, UMR 6285 CNRS, ENIB, 29200 Brest, France;
- Applied Physics Lab, Faculty of Science, Lebanese University, Campus Fanar, Jdeideh, Lebanon
| | - Elie Al Ahmar
- Faculty of Engineering, Sagesse University, Furn El Chebbak, Baabda, Lebanon;
| | - Elias Estephan
- Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon;
- Faculty of Engineering, Sagesse University, Furn El Chebbak, Baabda, Lebanon;
- Bioengineering Nanoscience Laboratory UR_UM104 (LBN), Montpellier University, 545 Avenue Prof. Viala, 34193 Montpellier Cedex, France
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Camilleri M, Jencks K. Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism. Expert Opin Drug Metab Toxicol 2024; 20:319-332. [PMID: 38785066 PMCID: PMC11139426 DOI: 10.1080/17425255.2024.2349716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/26/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Medications are frequently prescribed for patients with irritable bowel syndrome (IBS) or disorders of gut brain interaction. The level of drug metabolism and modifications in drug targets determine medication efficacy to modify motor or sensory function as well as patient response outcomes. AREAS COVERED The literature search included PubMed searches with the terms: pharmacokinetics, pharmacogenomics, epigenetics, clinical trials, irritable bowel syndrome, disorders of gut brain interaction, and genome-wide association studies. The main topics covered in relation to irritable bowel syndrome were precision medicine, pharmacogenomics related to drug metabolism, pharmacogenomics related to mechanistic targets, and epigenetics. EXPERT OPINION Pharmacogenomics impacting drug metabolism [CYP 2D6 (cytochrome P450 2D6) or 2C19 (cytochrome P450 2C19)] is the most practical approach to precision medicine in the treatment of IBS. Although there are proof of concept studies that have documented the importance of genetic modification of transmitters or receptors in altering responses to medications in IBS, these principles have rarely been applied in patient response outcomes. Genome-wide association (GWAS) studies have now documented the association of symptoms with genetic variation but not the evaluation of treatment responses. Considerably more research, particularly focused on patient response outcomes and epigenetics, is essential to impact this field in clinical medicine.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Kara Jencks
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Chang X, Zhang H, Chen S. Neural circuits regulating visceral pain. Commun Biol 2024; 7:457. [PMID: 38615103 PMCID: PMC11016080 DOI: 10.1038/s42003-024-06148-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 04/05/2024] [Indexed: 04/15/2024] Open
Abstract
Visceral hypersensitivity, a common clinical manifestation of irritable bowel syndrome, may contribute to the development of chronic visceral pain, which is a major challenge for both patients and health providers. Neural circuits in the brain encode, store, and transfer pain information across brain regions. In this review, we focus on the anterior cingulate cortex and paraventricular nucleus of the hypothalamus to highlight the progress in identifying the neural circuits involved in visceral pain. We also discuss several neural circuit mechanisms and emphasize the importance of cross-species, multiangle approaches and the identification of specific neurons in determining the neural circuits that control visceral pain.
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Affiliation(s)
- Xiaoli Chang
- College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Research Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
| | - Haiyan Zhang
- Research Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Shaozong Chen
- Research Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
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Lai TT, Liou CW, Tsai YH, Lin YY, Wu WL. Butterflies in the gut: the interplay between intestinal microbiota and stress. J Biomed Sci 2023; 30:92. [PMID: 38012609 PMCID: PMC10683179 DOI: 10.1186/s12929-023-00984-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 11/06/2023] [Indexed: 11/29/2023] Open
Abstract
Psychological stress is a global issue that affects at least one-third of the population worldwide and increases the risk of numerous psychiatric disorders. Accumulating evidence suggests that the gut and its inhabiting microbes may regulate stress and stress-associated behavioral abnormalities. Hence, the objective of this review is to explore the causal relationships between the gut microbiota, stress, and behavior. Dysbiosis of the microbiome after stress exposure indicated microbial adaption to stressors. Strikingly, the hyperactivated stress signaling found in microbiota-deficient rodents can be normalized by microbiota-based treatments, suggesting that gut microbiota can actively modify the stress response. Microbiota can regulate stress response via intestinal glucocorticoids or autonomic nervous system. Several studies suggest that gut bacteria are involved in the direct modulation of steroid synthesis and metabolism. This review provides recent discoveries on the pathways by which gut microbes affect stress signaling and brain circuits and ultimately impact the host's complex behavior.
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Affiliation(s)
- Tzu-Ting Lai
- Department of Physiology, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
| | - Chia-Wei Liou
- Department of Physiology, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
| | - Yu-Hsuan Tsai
- Department of Physiology, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
| | - Yuan-Yuan Lin
- Department of Physiology, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan
| | - Wei-Li Wu
- Department of Physiology, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan.
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan.
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Diao Z, Xu W, Guo D, Zhang J, Zhang R, Liu F, Hu Y, Ma Y. Causal association between psycho-psychological factors, such as stress, anxiety, depression, and irritable bowel syndrome: Mendelian randomization. Medicine (Baltimore) 2023; 102:e34802. [PMID: 37653741 PMCID: PMC10470701 DOI: 10.1097/md.0000000000034802] [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: 03/15/2023] [Revised: 07/18/2023] [Accepted: 07/27/2023] [Indexed: 09/02/2023] Open
Abstract
BACKGROUND Pathogenesis, diagnosis, and treatment of irritable bowel syndrome (IBS) have been reported to be challenging hotspots in clinical practice. Previous observational studies have found that stress, anxiety, depression, and other mental and psychological diseases are closely associated with IBS. This study aimed to further explore the causal relationships of these associations through Mendelian randomization (MR). METHODS The data needed for MR were obtained from publicly published genome-wide association databases. We performed a bidirectional, 2-sample MR analysis using instrumental variables (IV) associated with stress, anxiety, and depression, and other mental and psychological factors as exposures and IBS as the outcome. A reverse MR analysis with IBS as exposure and stress, anxiety, depression, and other mental and psychological factors as the outcomes was also performed. The inverse variance weighting (IVW) method was adopted as the main method of MR, and the causal effect between stress, anxiety, depression, and other mental and psychological factors and IBS was evaluated as the main result of the study. In addition, a series of sensitivity analyses was conducted to comprehensively evaluate the causal relationship between them. RESULTS Stress, anxiety, depression, and other mental and psychological factors were the underlying etiologies for IBS (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.03-1.08), and they were positively correlated. Univariate analysis further supported the above conclusions (Depression, [OR = 1.31, 95% CI: 1.05-1.63, P = .016], Anxiety, [OR = 1.53, 95% CI: 1.16-2.03, P = .003]). However, in reverse MR analysis, we found that IBS did not affect stress, anxiety, depression, or other mental and psychological factors and that there was no causal relationship between IBS and stress, anxiety, depression, or other mental and psychological factors (P > .05). CONCLUSION This study demonstrates that mental and psychological factors are the underlying etiologies for IBS. These findings may provide important information for physicians regarding the clinical treatment of IBS.
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Affiliation(s)
- Zhihao Diao
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wenchang Xu
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Danyang Guo
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jingzhi Zhang
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ruiyu Zhang
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Fengzhao Liu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yufei Hu
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuxia Ma
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Singh SV, Ganguly R, Jaiswal K, Yadav AK, Kumar R, Pandey AK. Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review. World J Clin Cases 2023; 11:4458-4476. [PMID: 37469740 PMCID: PMC10353503 DOI: 10.12998/wjcc.v11.i19.4458] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/30/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.
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Affiliation(s)
- Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Aditya Kumar Yadav
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
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Gu Y, Lai YT, Chang FR, Chen CY. Utilization patterns and prescription characteristics of traditional Chinese medicine among patients with irritable bowel syndrome in Taiwan. Front Pharmacol 2023; 14:1201240. [PMID: 37397480 PMCID: PMC10311911 DOI: 10.3389/fphar.2023.1201240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 06/05/2023] [Indexed: 07/04/2023] Open
Abstract
Background: Few studies have investigated traditional Chinese medicine (TCM) utilization patterns for irritable bowel syndrome (IBS), despite the potential benefits of exploring TCM utilization patterns in optimizing TCM management. This study aimed to evaluate TCM utilization patterns and clinical features for IBS patterns in Taiwan. Methods: This was a population-based cross-sectional study using claim data from the National Health Insurance Research Database between 2012 and 2018. Patients newly diagnosed with IBS and aged over 20 years were included. The TCM utilization patterns and characteristics, including Chinese herbal medicine (CHM) treatment types and prescription patterns, were evaluated. Results: A total of 73,306 patients newly diagnosed with IBS used TCM for IBS at least once. Females used TCM for IBS more than males (female-to-male ratio = 1.89: 1). The age distribution showed a peak at 30-39 years (27.29%), followed by 40-49 years (20.74%) and 20-29 years (20.71%). Patients who received Western medications for IBS had a lower tendency to seek TCM. CHM was the most commonly used TCM modality (98.22%), with Jia-wei-xiao-yao-san being the most commonly prescribed Chinese herbal formula and Bai-zhu being the most frequently prescribed single Chinese herb. Conclusion: This study enhances our understanding of TCM usage patterns for IBS, particularly CHM prescriptions. Further research is needed to investigate commonly used TCM formulas and individual herbs.
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Affiliation(s)
- Ye Gu
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Tung Lai
- Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Drug Development and Value Creation Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Yu Chen
- Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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8
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Labrenz F, Merz CJ, Icenhour A. Connecting dots in disorders of gut-brain interaction: the interplay of stress and sex hormones in shaping visceral pain. Front Psychiatry 2023; 14:1204136. [PMID: 37275987 PMCID: PMC10235543 DOI: 10.3389/fpsyt.2023.1204136] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 05/02/2023] [Indexed: 06/07/2023] Open
Abstract
Visceral pain and stress are tightly intertwined bodily and emotional phenomena, which enable a flexible adaptation to environmental challenges by activating a response repertoire to restore homeostasis along the gut-brain axis. However, visceral pain and stress can persist widely independent of the initial cause, acquiring independent disease values and posing major health burdens as predominant features in disorders of gut-brain interaction (DGBI). Epidemiological data consistently documents an increased prevalence for women to suffer from chronic visceral pain, possibly shaped by sex hormones and modulated by stress and its biological and psychosocial correlates. Yet, mechanisms underlying the complex interactions between altered visceroception, stress and sex remain widely elusive, especially in clinical populations with DGBI. We herein selectively review mechanisms of interactions between stress and sex in the complex pathophysiology of DGBI. A particular emphasis is laid on visceral pain, in which stress constitutes a major risk factor as well as mediator, and sex-related differences are particularly pronounced. Building on the neurobiology of stress and mechanisms of gut-brain interactions, we highlight putative target mechanisms via which visceral pain and stress may converge with sex effects into a triad. Accommodating a global demographic shift, we propose a lifespan perspective in future research, which may enable a more fine-tuned evaluation of this complex interplay exerting distinct challenges during vulnerable developmental phases. This viewpoint may advance our understanding of pathophysiological processes and can ultimately inspire novel tailored prevention strategies and therapeutic approaches in the treatment of chronic visceral pain and DGBI across the lifespan.
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Affiliation(s)
- Franziska Labrenz
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Christian J. Merz
- Department of Cognitive Psychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany
| | - Adriane Icenhour
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
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Groeger D, Murphy EF, Tan HTT, Larsen IS, O'Neill I, Quigley EMM. Interactions between symptoms and psychological status in irritable bowel syndrome: An exploratory study of the impact of a probiotic combination. Neurogastroenterol Motil 2023; 35:e14477. [PMID: 36178333 PMCID: PMC10078522 DOI: 10.1111/nmo.14477] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 04/06/2022] [Accepted: 09/20/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Stress is an exacerbator of irritable bowel syndrome (IBS) symptoms, and anxiety and depression are co-morbidities. Bifidobacterium longum strains 1714® and 35642® attenuate stress responses in healthy people and reduce symptoms in IBS, respectively. Here, we explore relationships between the psychological and visceral effects of the two strains (COMBO) in IBS subjects and biomarkers of stress and inflammation. METHODS We recruited 40 patients with IBS (Rome III) and mild to moderate anxiety (HADS-A) and/or depression (HADS-D) and 57 asymptomatic female controls with low or moderate stress. IBS patients were fed COMBO (1 × 109 cfu/day) for 8 weeks with an 8-week washout. IBS symptoms, psychometric measures, salivary cortisol awakening response (CAR), and plasma inflammatory biomarkers were assessed every 4 weeks. KEY RESULTS Compared to healthy controls, IBS subjects had a blunted CAR. Treatment with COMBO restored CAR and improved IBS symptoms compared to baseline during the treatment phase. The COMBO reduced HADS-D, HADS-A score, and TNF-α, while sleep quality improved significantly from baseline to the end of the intervention. Surprisingly, these parameters improved further once treatment ended and maintained this improvement by Week 16. CONCLUSIONS AND INFERENCES These findings suggest that the stress response is a major driver of IBS symptoms. The time course of the beneficial effect of COMBO on IBS symptoms suggests that this is achieved through a restoration of the stress response. In contrast, the time course of the effects of COMBO on anxiety and depression in IBS paralleled an anti-inflammatory effect as indicated by a reduction in circulating levels of TNF-α.
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Affiliation(s)
| | | | | | | | - Ian O'Neill
- Department of Microbiology, APC Microbiome IrelandNational University of IrelandCorkIreland
| | - Eamonn M. M. Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist HospitalWeill Cornell Medical CollegeHoustonTexasUSA
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10
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Hinse M, Thronicke A, Berghöfer A, Matthes H. New multimodal intervention to reduce irritable bowel syndrome (IBS) severity symptoms-Pilot study with a 12 month follow-up. PLoS One 2022; 17:e0277880. [PMID: 36409730 PMCID: PMC9678296 DOI: 10.1371/journal.pone.0277880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 10/25/2022] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is characterized by patients' high level of suffering. Up to 60% of patients with IBS have symptoms of anxiety or depression and only little attention has been paid to their specific requirements. Anthroposophical multimodal therapy (AMT) has been shown to significantly improve health-related quality of life of patients with high symptomatic burden. OBJECTIVE The aim of this pilot study was to find out whether AMT meets the needs of IBS patients and the interactions of AMT with IBS, depression and anxiety. METHODS Patients with diagnosed IBS were included in a feasibility study and received 12 sessions of AMT over 8 weeks (drks.de, DRKS00016890). The primary endpoint was the change of the IBS severity score (IBS-SSS) and changes were calculated by linear mixed effects analyses. The secondary endpoints were changes of self-reported PHQ-9 and GAD-7 for mental comorbidity as well as self-valued effectiveness and satisfaction of AMT. RESULTS Thirty-six patients, 89% female, were included in the study. AMT was successfully applied to IBS patients (-45 points in the IBS-SSS, p < .05). AMT had a large positive effect (-84 points in IBS-SSS, p < .003) on patients without anxiety or depression. Over time, patients with higher anxiety scores worsened with regard to their IBS compared to patients with depression and without mental comorbidity. The AMT effect was maintained at a 12 month follow up and both mentally affected and unaffected patients, had even lower IBS severity than shortly after AMT. AMT modules were rated by IBS patients as very effective. CONCLUSION Our findings suggest that an 8-week program of AMT improves the severity of IBS with an ongoing effect at a 12 month follow-up. Especially for patients without psychological comorbidities, AMT is very successful. Future IBS therapies should incorporate a modified multimodal concept with stronger psychological therapy modules in parallel for patients with depression and anxiety.
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Affiliation(s)
- Maximilian Hinse
- Institute of Social Medicine, Epidemiology and Health Economy, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Anja Thronicke
- Institute of Social Medicine, Epidemiology and Health Economy, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Research Institute Havelhöhe at the Hospital Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany
| | - Anne Berghöfer
- Institute of Social Medicine, Epidemiology and Health Economy, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Harald Matthes
- Institute of Social Medicine, Epidemiology and Health Economy, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Research Institute Havelhöhe at the Hospital Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany
- Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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11
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Zhang G, Zhang T, Cao Z, Tao Z, Wan T, Yao M, Su X, Wei W. Effects and Mechanisms of Acupuncture on Diarrhea-Predominant Irritable Bowel Syndrome: A Systematic Review. Front Neurosci 2022; 16:918701. [PMID: 35911986 PMCID: PMC9334728 DOI: 10.3389/fnins.2022.918701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/20/2022] [Indexed: 11/28/2022] Open
Abstract
Background Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with challenging treatment. According to evidence-based studies, acupuncture is likely to be a promising therapy and subservient adjunct for IBS. Mechanism study of acupuncture based on related clinical trials of high quality, nevertheless, is still vacant. Aim This study aims to assess the results and qualities of current clinical evidence and conclude the relevant pathophysiological mechanisms and therapeutic effects of acupuncture on IBS with diarrhea (IBS-D). Methods Literature from four databases, namely, PubMed, Cochrane Library, EMBASE, and Web of Science, was systematically searched to obtain eligible randomized controlled trials (RCTs), which contained mechanism research of acupuncture treatment in IBS-D patients. Two independent reviewers completed data extraction and quality evaluation using the RevMan 5.4.1 software. Results Ten trials that covered 19 items related to mechanism research were included in this review. Acupuncture was reported to improve IBS-D symptoms and quality of life, with positive effects in regulating brain-gut peptides, cerebral activities, neuroendocrine functions, psychological state, and inflammatory GI and hypersensitive intestinal tracts. Conclusion Acupuncture has potential influence on pathophysiology alterations such as regulating brain-gut peptides, altering cerebral connectivity and activity, promoting neuroendocrine functions and mental state, and mitigating inflammation as well as hypersensitivity of bowels in IBS-D patients, but further studies of high quality are still necessary. Systematic Review Registration [https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022320331].
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Affiliation(s)
- Gezhi Zhang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Tao Zhang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Zeng Cao
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Zijing Tao
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Tianhao Wan
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Mengxi Yao
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Xiaolan Su
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
- *Correspondence: Xiaolan Su,
| | - Wei Wei
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
- Wei Wei,
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12
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Wan Y, Zhang B. The Impact of Zinc and Zinc Homeostasis on the Intestinal Mucosal Barrier and Intestinal Diseases. Biomolecules 2022; 12:biom12070900. [PMID: 35883455 PMCID: PMC9313088 DOI: 10.3390/biom12070900] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/06/2022] [Accepted: 06/11/2022] [Indexed: 02/04/2023] Open
Abstract
Zinc is an essential trace element for living organisms, and zinc homeostasis is essential for the maintenance of the normal physiological functions of cells and organisms. The intestine is the main location for zinc absorption and excretion, while zinc and zinc homeostasis is also of great significance to the structure and function of the intestinal mucosal barrier. Zinc excess or deficiency and zinc homeostatic imbalance are all associated with many intestinal diseases, such as IBD (inflammatory bowel disease), IBS (irritable bowel syndrome), and CRC (colorectal cancer). In this review, we describe the role of zinc and zinc homeostasis in the intestinal mucosal barrier and the relevance of zinc homeostasis to gastrointestinal diseases.
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13
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Emotional stress responsivity of patients with IBS - a systematic review. J Psychosom Res 2022; 153:110694. [PMID: 34942583 DOI: 10.1016/j.jpsychores.2021.110694] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 11/20/2022]
Abstract
OBJECTIVE Irritable bowel syndrome (IBS) is a highly prevalent disorder of the gut-brain interaction characterized by abdominal discomfort and pain associated with altered bowel habits in the absence of structural abnormalities. Chronic psychological stress is considered a risk factor for the development of IBS. The multifactorial pathogenesis involves complex interactions between biological, psychological and social factors, yet the underlying mechanisms have not been fully understood. METHODS We systematically reviewed the literature from the databases MEDLINE, Embase and PsycINFO to assess stress responsivity of patients with IBS in comparison to healthy individuals, specifically focusing acute psychological stressors. RESULTS A total of 37 case-control studies were included in the narrative synthesis. Findings comprised subjective changes in emotion (k = 18) and of gastrointestinal symptoms (k = 8) as well as objective parameters of gastrointestinal motility (k = 10), autonomic nervous system (k = 23), hypothalamic-pituitary-adrenal axis (k = 11), functional brain activity (k = 7) and immune system (k = 3). Mental stress was found to increase IBS-specific symptomatology and alter gastrointestinal motility. Some patients with IBS showed stress-induced emotional hyperresponsivity and different patterns of neural activation. Autonomic and endocrine stress responses depend on the type of stressor and showed no clear evidence of differential reactivity, partly due to confounding factors. Data on acute immunological changes remains sparse and requires further investigation. CONCLUSIONS Current evidence suggests altered stress reactivity in patients with IBS however, it remains unclear whether it can be attributed to the syndrome itself or the high prevalence of psychiatric comorbidities.
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14
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Kim KO. [Functional Gastrointestinal Disorders in Patients with Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2022; 79:4-11. [PMID: 35086967 DOI: 10.4166/kjg.2022.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 01/22/2022] [Accepted: 01/24/2022] [Indexed: 11/03/2022]
Abstract
With emerging more effective drugs, the therapeutic goal of inflammatory bowel disease (IBD) has progressed from clinical remission to mucosal healing. Although the inflammation could be controlled more effectively than before, symptoms such as abdominal pain and bowel habit change is still bothersome to some IBD patients. Recently, these "refractory functional gastrointestinal symptoms" in quiescent IBD patients has been paid more attention. The pathophysiology could be multifactorial with genetics, change in gut motility associated with post inflammatory condition, increased permeability, impaired colorectal function, visceral hypersensitivity and gut microbiota. Because both IBD and functional gastrointestinal disease (FGID) could share similar symptoms and some pathophysiology, it is sometimes challenging to distinguish them exactly. However, to reduce the risk of overtreatment or insufficient control of inflammation, exact diagnosis of functional disease or symptoms in quiescent IBD patients is important. Because there is limited randomized controlled trials or prospective study currently, most of the therapeutic approach in IBD patients are empirical or referred to those of functional gastrointestinal disorders. However, approaches based on pathophysiological mechanisms could give appropriate therapies for both IBD and FGIDs.
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Affiliation(s)
- Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
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15
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Louwies T, Meerveld BGV. Abdominal Pain. COMPREHENSIVE PHARMACOLOGY 2022:132-163. [DOI: 10.1016/b978-0-12-820472-6.00037-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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16
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Davey S, Halberstadt J, Bell E. Where is emotional feeling felt in the body? An integrative review. PLoS One 2021; 16:e0261685. [PMID: 34936672 PMCID: PMC8694467 DOI: 10.1371/journal.pone.0261685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 12/07/2021] [Indexed: 11/22/2022] Open
Abstract
Contemporary research on "embodied emotion" emphasizes the role of the body in emotional feeling. The evidence base on interoception, arguably the most prominent strand of embodied emotion research, places emphasis on the cardiac, respiratory and gastrointestinal systems. In turn, interoception has evidence-based links with improved emotion regulation. Despite the focus on separate bodily systems, it is unclear whether particular interoceptive locations play a greater role in emotional feeling and emotion regulation. Further, according to Gross' "process model", the sooner that regulation of an emotion occurs, the better; hence, it is additionally important to identify the first body areas to activate. These issues are investigated in a two-stage integrative review. The first stage was preliminary, giving an overview of the evidence base to highlight the distribution of measured body areas. This indicated that 86% of publications (n = 88) measured cardiac activity, 26% measured the respiratory system, and six percent the gastrointestinal system. Given the emphasis placed on all three systems in interoception theory and research on emotion, this suggests a dearth of comprehensive findings pertaining to feeling locations. The second stage investigated the core issues of where emotional feelings are felt in the body and time-related implications for regulation. This was based on ten texts, which together suggested that the head, throat and chest are the most consistently detected locations across and within numerous emotional contexts. Caution is required, however, since-among other reasons discussed-measurement was not time-restricted in these latter publications, and direct physiological measurement was found in only a minority of cases.
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Affiliation(s)
- Steven Davey
- Department of Psychological Medicine, University of Otago Wellington, Wellington, New Zealand
| | | | - Elliot Bell
- Department of Psychological Medicine, University of Otago, Wellington, New Zealand
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17
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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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18
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Videlock EJ, Chang L. Latest Insights on the Pathogenesis of Irritable Bowel Syndrome. Gastroenterol Clin North Am 2021; 50:505-522. [PMID: 34304785 DOI: 10.1016/j.gtc.2021.04.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The pathogenesis of irritable bowel syndrome is multifactorial and complex. Our understanding of its pathophysiology has evolved, but remains incompletely understood. Symptoms result from a dysregulation of brain-gut interactions. Evidence has identified alterations in central and peripheral (gut) mechanisms in irritable bowel syndrome and the bidirectional communication between the brain and the gut. Pertinent mechanisms include disturbed gut motility, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing. This review addresses factors that increase the risk of irritable bowel syndrome and the central and peripheral mechanisms thought to underlie its symptoms.
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Affiliation(s)
- Elizabeth J Videlock
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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19
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Cayoun BA, Shires AG. Co-emergence Reinforcement and Its Relevance to Interoceptive Desensitization in Mindfulness and Therapies Aiming at Transdiagnostic Efficacy. Front Psychol 2020; 11:545945. [PMID: 33414739 PMCID: PMC7783049 DOI: 10.3389/fpsyg.2020.545945] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 11/30/2020] [Indexed: 12/18/2022] Open
Abstract
Interoception, the ability to feel the body's internal sensations, is an essential aspect of emotional experience. There is mounting evidence that interoception is impaired in common mental health disorders and that poor interoceptive awareness is a major contributor to emotional reactivity, calling for clinical interventions to address this deficit. The manuscript presents a comprehensive theoretical review, drawing on multidisciplinary findings to propose a metatheory of reinforcement mechanisms applicable across a wide range of disorders. We present a reconsideration of operant conditioning through the co-emergence model of reinforcement, which is a neurophenomenological account of the interaction between cognition and interoception, and its consequences on behavior. The model suggests that during memory processing, the retrieval of autobiographical memory (including maladaptive cognition) is dependent upon its co-emerging interoceptive cues occurring at the encoding, consolidation and reconsolidation stages. Accordingly, "interoceptive reinforcement" during emotional distress is a common factor to all emotional disorders and a major cause for relapse. We propose that interoceptive desensitization has transdiagnostic benefits, readily achievable through the cultivation of equanimity during mindfulness training and can be integrated in cognitive and behavioral interventions to permit a transdiagnostic applicability. We summarize the contributions of this approach into 10 specific and testable propositions.
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Affiliation(s)
| | - Alice G. Shires
- Mindfulness Integrated Therapies and Research Clinic, University of Technology Sydney, Ultimo, NSW, Australia
- School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
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20
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Koloski N, Holtmann G, Talley NJ. Is there a causal link between psychological disorders and functional gastrointestinal disorders? Expert Rev Gastroenterol Hepatol 2020; 14:1047-1059. [PMID: 32715790 DOI: 10.1080/17474124.2020.1801414] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Psychological distress is associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD) but only evidence from prospective longitudinal and treatment studies can indicate whether the link between FGIDs and psychological distress is causal. Emerging evidence suggests underlying biological mechanisms may explain the association of psychological distress with FGIDs. AREAS COVERED This review critically evaluates whether anxiety and/or depression and FGIDs are causally related including evidence for a temporal sequence, strength and specificity of the association, biological gradient, and biological plausibility. EXPERT OPINION Accumulating evidence suggests that psychological factors are causal for symptoms in a subset of FGID patients and not explained by health care seeking behavior (brain-gut disorder). In other cases, psychological factors may arise secondary to intestinal disease (gut-brain disorder). Prospective population-based studies are needed in FGIDs other than IBS and FD to determine if a similar brain-gut and gut-brain syndrome exists. Treatment studies have not phenotyped FGIDs according to brain-gut versus gut-brain origins which may be important in understanding true treatment efficacy. Future research needs to unravel biological mechanisms that may explain the link between psychological factors and FGIDs but promising data in the area of the brain-gut-immune-microbe axis is emerging.
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Affiliation(s)
- Natasha Koloski
- Faculty of Health and Medicine, University of Newcastle , Callaghan, Australia
- Australian Gastrointestinal Research Alliance (AGIRA)
- Department of Gastroenterology, Princess Alexandra Hospital , Woolloongabba, Australia
- School of Medicine, University of Queensland , St Lucia, Australia
| | - Gerald Holtmann
- Australian Gastrointestinal Research Alliance (AGIRA)
- Department of Gastroenterology, Princess Alexandra Hospital , Woolloongabba, Australia
- School of Medicine, University of Queensland , St Lucia, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle , Callaghan, Australia
- Australian Gastrointestinal Research Alliance (AGIRA)
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21
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Luo QQ, Wang B, Chen X, Qiu HY, Li WT, Yan XJ, Chen SL. Acute stress induces visceral hypersensitivity via glucocorticoid receptor-mediated membrane insertion of TRPM8: Involvement of a non-receptor tyrosine kinase Pyk2. Neurogastroenterol Motil 2020; 32:1514-1528. [PMID: 32391653 DOI: 10.1111/nmo.13877] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Revised: 03/05/2020] [Accepted: 04/17/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Psychological stress is an important factor for the development and recurrence of irritable bowel syndrome (IBS). The mechanisms underlying stress-induced visceral hypersensitivity (VH), a key pathophysiological component in IBS, are still incompletely understood. We aimed to test whether transient receptor potential melastatin 8 (TRPM8) participates in acute stress-induced VH. METHODS Rats were subjected to 1-hour water avoidance stress (WAS). Visceral sensitivity was measured with visceromotor response to colorectal distension. Western blot and immunofluorescence were applied to evaluate the expression of GR and TRPM8 and activation of PKA, Akt, and PKC pathways. RESULTS WAS-caused VH depended on glucocorticoid receptors (GRs) and TRPM8 channels. In a dorsal root ganglion (DRG)-derived cell line, corticosterone rapidly (within 30 minutes) induced membrane expression of TRPM8. This effect was inhibited by GR antagonism and was mimicked by membrane-impermeable corticosterone. PKA, PI3K/Akt, and PKC pathways, which lied downstream of GR and acted in parallel to promote membrane expression of TRPM8, contributed to WAS-induced VH. The non-receptor tyrosine kinase Pyk2, which may serve as a convergence point for PKA, PI3K/Akt, and PKC pathways, facilitated membrane insertion of TRPM8 via tyrosine-phosphorylating TRPM8 in L6-S2 DRGs and participated in WAS-induced VH. CONCLUSIONS Collectively, acute stress-induced VH could involve membrane-bound GR-dependent enhancement of TRPM8 function in nociceptive DRG neurons. Mechanistically, Pyk2 could act as a key mediator that coordinates multiple protein kinase signaling and triggers phosphorylation and membrane insertion of TRPM8.
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Affiliation(s)
- Qing-Qing Luo
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Bo Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xin Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Hong-Yi Qiu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Wen-Ting Li
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiu-Juan Yan
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Sheng-Liang Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
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22
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Li JJ, Ren WJ, Yin HY, Zhao YF, Tang Y. Underlying mechanisms for intestinal diseases arising from stress. Shijie Huaren Xiaohua Zazhi 2020; 28:617-627. [DOI: 10.11569/wcjd.v28.i14.617] [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] [Indexed: 02/06/2023] Open
Abstract
Stress is an instinctive defense mechanism of the body in the competition for survival, but long-term or chronic stress will lead to systemic pathological manifestations. Intestinal diseases are closely related to pathological stress. This paper reviews the pathogenesis of intestinal diseases arising from stress.
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Affiliation(s)
- Jia-Jia Li
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China,Key Laboratory of Sichuan Province for Acupuncture and Chronobiology, Chengdu 610075, Sichuan Province, China
| | - Wen-Jing Ren
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China,Key Laboratory of Sichuan Province for Acupuncture and Chronobiology, Chengdu 610075, Sichuan Province, China
| | - Hai-Yan Yin
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China,Key Laboratory of Sichuan Province for Acupuncture and Chronobiology, Chengdu 610075, Sichuan Province, China
| | - Ya-Fei Zhao
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China,Key Laboratory of Sichuan Province for Acupuncture and Chronobiology, Chengdu 610075, Sichuan Province, China
| | - Yong Tang
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China,Key Laboratory of Sichuan Province for Acupuncture and Chronobiology, Chengdu 610075, Sichuan Province, China
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23
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Ji Y, Hu B, Klontz C, Li J, Dessem D, Dorsey SG, Traub RJ. Peripheral mechanisms contribute to comorbid visceral hypersensitivity induced by preexisting orofacial pain and stress in female rats. Neurogastroenterol Motil 2020; 32:e13833. [PMID: 32155308 PMCID: PMC7319894 DOI: 10.1111/nmo.13833] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 01/24/2020] [Accepted: 02/18/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Stress exacerbates many chronic pain syndromes including irritable bowel syndrome (IBS). Among these patient populations, many suffer from comorbid or chronic overlapping pain conditions and are predominantly female. Nevertheless, basic studies investigating chronic psychological stress-induced changes in pain sensitivity have been mostly carried out in male rodents. Our laboratory developed a model of comorbid pain hypersensitivity (CPH) (stress in the presence of preexisting orofacial pain inducing chronic visceral pain hypersensitivity that significantly outlasts transient stress-induced pain hypersensitivity (SIH)) facilitating the study of pain associated with IBS. Since CPH and SIH are phenotypically similar until SIH resolves and CPH persists, it is unclear if underlying mechanisms are similar. METHODS In the present study, the visceromotor response (VMR) to colorectal distention was recorded in the SIH and CPH models in intact females and ovariectomized rats plus estradiol replacement (OVx + E2). Over several months, rats were determined to be susceptible or resilient to stress and the role of peripheral corticotrophin-releasing factor (CRF) underlying in the pain hypersensitivity was examined. KEY RESULTS Stress alone induced transient (3-4 weeks) visceral hypersensitivity, though some rats were resilient. Comorbid conditions increased susceptibility to stress prolonging hypersensitivity beyond 13 weeks. Both models had robust peripheral components; hypersensitivity was attenuated by the CRF receptor antagonist astressin and the mast cell stabilizer disodium cromoglycate (DSCG). However, DSCG was less effective in the CPH model compared to the SIH model. CONCLUSIONS AND INFERENCES The data indicate many similarities but some differences in mechanisms contributing to comorbid pain conditions compared to transient stress-induced pain.
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Affiliation(s)
- Yaping Ji
- Department of Neural and Pain SciencesSchool of DentistryUniversity of Maryland BaltimoreBaltimoreMDUSA
| | - Bo Hu
- Department of Neural and Pain SciencesSchool of DentistryUniversity of Maryland BaltimoreBaltimoreMDUSA,Present address:
Key laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchXi’an Jiao Tong University College of StomatologyXi’anShaanxiChina
| | - Charles Klontz
- Department of Neural and Pain SciencesSchool of DentistryUniversity of Maryland BaltimoreBaltimoreMDUSA
| | - Jiyun Li
- Department of Neural and Pain SciencesSchool of DentistryUniversity of Maryland BaltimoreBaltimoreMDUSA
| | - Dean Dessem
- Department of Neural and Pain SciencesSchool of DentistryUniversity of Maryland BaltimoreBaltimoreMDUSA,UM Center to Advance Chronic Pain ResearchUniversity of Maryland BaltimoreBaltimoreMDUSA
| | - Susan G. Dorsey
- UM Center to Advance Chronic Pain ResearchUniversity of Maryland BaltimoreBaltimoreMDUSA,Department of Pain and Translational Symptom ScienceSchool of NursingUniversity of Maryland BaltimoreBaltimoreMDUSA
| | - Richard J. Traub
- Department of Neural and Pain SciencesSchool of DentistryUniversity of Maryland BaltimoreBaltimoreMDUSA,UM Center to Advance Chronic Pain ResearchUniversity of Maryland BaltimoreBaltimoreMDUSA
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Wu H, Huang Y, Tian X, Zhang Z, Zhang Y, Mao Y, Wang C, Yang S, Liu Y, Zhang W, Ma Z. Preoperative anxiety-induced glucocorticoid signaling reduces GABAergic markers in spinal cord and promotes postoperative hyperalgesia by affecting neuronal PAS domain protein 4. Mol Pain 2020; 15:1744806919850383. [PMID: 31041873 PMCID: PMC6537253 DOI: 10.1177/1744806919850383] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Preoperative anxiety is common in patients undergoing elective surgery and is
closely related to postoperative hyperalgesia. In this study, a single prolonged
stress model was used to induce preoperative anxiety-like behavior in rats 24 h
before the surgery. We found that single prolonged stress exacerbated the
postoperative pain and elevated the level of serum corticosterone. Previous
studies have shown that glucocorticoid is associated with synaptic plasticity,
and decreased spinal GABAergic activity can cause hyperalgesia in rodents. Here,
single prolonged stress rats’ lumbar spinal cord showed reduced glutamic acid
decarboxylase-65, glutamic acid decarboxylase-67, GABA type A receptor alpha 1
subunit, and GABA type A receptor gamma 2 subunit, indicating an impairment of
GABAergic system. Furthermore, neuronal PAS domain protein 4 was also reduced in
rats after single prolonged stress stimulation, which has been reported to
promote GABAergic synapse development. Then, intraperitoneal injection of RU486
(a glucocorticoid receptor antagonist) rather than spironolactone (a
mineralocorticoid receptor antagonist) was found to relieve single prolonged
stress-induced hyperalgesia and reverse neuronal PAS domain protein 4 reduction
and the impairment of GABAergic system. Furthermore, overexpressing neuronal PAS
domain protein 4 could also restore the damage of GABAergic system caused by
single prolonged stress while interfering with neuronal PAS domain protein 4
caused an opposite effect. Finally, after stimulation of rat primary spinal cord
neurons with exogenous corticosterone in vitro, neuronal PAS domain protein 4
and GABAergic markers were also downregulated, and RU486 reversed that.
Together, our results demonstrated that preoperative anxiety led to GABAergic
system impairment in spinal cord and thus caused hyperalgesia due to
glucocorticoid-induced downregulation of neuronal PAS domain protein 4.
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Affiliation(s)
- Hao Wu
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Yulin Huang
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Xinyu Tian
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Zuoxia Zhang
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Ying Zhang
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Yanting Mao
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Chenchen Wang
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Shuai Yang
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Yue Liu
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Wei Zhang
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
| | - Zhengliang Ma
- 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
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Bulleyaconitine A Inhibits Visceral Nociception and Spinal Synaptic Plasticity through Stimulation of Microglial Release of Dynorphin A. Neural Plast 2020; 2020:1484087. [PMID: 32565774 PMCID: PMC7262664 DOI: 10.1155/2020/1484087] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 02/14/2020] [Accepted: 03/11/2020] [Indexed: 12/20/2022] Open
Abstract
Background Visceral pain is one of the most common types of pain and particularly in the abdomen is associated with gastrointestinal diseases. Bulleyaconitine A (BAA), isolated from Aconitum bulleyanum, is prescribed in China to treat chronic pain. The present study is aimed at evaluating the mechanisms underlying BAA visceral antinociception. Methods The rat model of chronic visceral hypersensitivity was set up by colonic perfusion of 2,4,6-trinitrobenzene sulfonic acid (TNBS) on postnatal day 10 with coapplication of heterotypic intermittent chronic stress (HeICS). Results The rat model of chronic visceral hypersensitivity exhibited remarkable abdominal withdrawal responses and mechanical hyperalgesia in hind paws, which were dose-dependently attenuated by single subcutaneous of administration of BAA (30 and 90 μg/kg). Pretreatment with the microglial inhibitor minocycline, dynorphin A antiserum, and κ-opioid receptor antagonist totally blocked BAA-induced visceral antinociception and mechanical antihyperalgesia. Spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn lamina II neurons were recorded by using whole-cell patch clamp. Its frequency (but not amplitude) from TNBS-treated rats was remarkably higher than that from naïve rats. BAA (1 μM) significantly reduced the frequency of sEPSCs from TNBS-treated rats but not naïve rats. BAA-inhibited spinal synaptic plasticity was blocked by minocycline, the dynorphin A antiserum, and κ-opioid receptor antagonist. Dynorphin A also inhibited spinal synaptic plasticity in a κ-opioid receptor-dependent manner. Conclusions These results suggest that BAA produces visceral antinociception by stimulating spinal microglial release of dynorphin A, which activates presynaptic κ-opioid receptors in afferent neurons and inhibits spinal synaptic plasticity, highlighting a novel interaction mode between microglia and neurons.
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26
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Ouyang X, Li S, Zhou J, Chen JDZ. Electroacupuncture Ameliorates Gastric Hypersensitivity via Adrenergic Pathway in a Rat Model of Functional Dyspepsia. Neuromodulation 2020; 23:1137-1143. [DOI: 10.1111/ner.13154] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 02/27/2020] [Accepted: 03/16/2020] [Indexed: 12/15/2022]
Affiliation(s)
- Xiaojun Ouyang
- Veterans Research and Education Foundation, Oklahoma City VA Health Care System OK USA
- Institute of Geriatrics, Jiangsu Province Official Hospital Nanjing Jiangsu China
| | - Shiying Li
- Veterans Research and Education Foundation, Oklahoma City VA Health Care System OK USA
- Division of Gastroenterology and Hepatology Johns Hopkins University Baltimore MD USA
| | - Jingzhu Zhou
- Veterans Research and Education Foundation, Oklahoma City VA Health Care System OK USA
- Department of Acupuncture and Moxibustion The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China
| | - Jiande DZ Chen
- Division of Gastroenterology and Hepatology Johns Hopkins University Baltimore MD USA
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27
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Huang SN, Yang B, Ma L, Huang LT, Ju PJ, Wei J, Ali U, Wang YX, Chen J. Bulleyaconitine A Exerts Antianxiety and Antivisceral Hypersensitivity Effects. Front Pharmacol 2020; 11:328. [PMID: 32265706 PMCID: PMC7098429 DOI: 10.3389/fphar.2020.00328] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 03/06/2020] [Indexed: 12/12/2022] Open
Abstract
Visceral pain is one of the leading causes for abdominal pain in gastroenterological diseases and is still hard to treat effectively. Bulleyaconitine A (BAA) is an aconitine analog and has been used for the treatment of pain. Our previous work suggested that BAA exerted analgesic effects on neuropathic pain through stimulating the expression of dynorphin A in spinal microglia. Here, we investigated the inhibitory effect of BAA on visceral pain and examined whether the expression of dynorphin A in spinal microglia was responsible for its effects. We found that BAA produced significant antivisceral pain effect induced by acetic acid through stimulating dynorphin A expression in spinal microglia. In addition, anxiety and chronic visceral pain are highly prevalent comorbid conditions in clinical research, which is still a problem to be solved. We also aimed to evaluate the effects of BAA on anxiety. A comorbidity model with characteristics of both chronic visceral pain and anxiety was developed by colorectal injection of 2,4,6-trinitrobenzene sulfonic acid and the induction of heterotypic intermittent chronic stress protocol. In comorbid animals, BAA exerted great antianxiety effects. Meanwhile, the antianxiety mechanism of BAA was different with the antivisceral pain mechanism of BAA. In conclusion, our study demonstrated, for the first time, that BAA exerted marked antivisceral pain and antianxiety effects, which expands the analgesic spectrum and clinical application of BAA. Furthermore, it also it provides a better guidance for the clinical use of BAA.
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Affiliation(s)
- Sheng-Nan Huang
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China.,Shanghai Jiao Tong University School of Pharmacy, Shanghai, China
| | - BeiBei Yang
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China
| | - Le Ma
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China.,Shanghai Jiao Tong University School of Pharmacy, Shanghai, China
| | - Lan-Ting Huang
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China
| | - Pei-Jun Ju
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China
| | - Jinbao Wei
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China.,Shanghai Jiao Tong University School of Pharmacy, Shanghai, China
| | - Usman Ali
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China.,Shanghai Jiao Tong University School of Pharmacy, Shanghai, China
| | - Yong-Xiang Wang
- Shanghai Jiao Tong University School of Pharmacy, Shanghai, China
| | - Jinghong Chen
- Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China
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28
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Kurahashi M, Kito Y, Baker SA, Jennings LK, Dowers JGR, Koh SD, Sanders KM. A novel postsynaptic signal pathway of sympathetic neural regulation of murine colonic motility. FASEB J 2020; 34:5563-5577. [PMID: 32086857 DOI: 10.1096/fj.201903134r] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/04/2020] [Accepted: 02/13/2020] [Indexed: 01/14/2023]
Abstract
Transcriptome data revealed α1 adrenoceptors (ARs) expression in platelet-derived growth factor receptor α+ cells (PDGFRα+ cells) in murine colonic musculature. The role of PDGFRα+ cells in sympathetic neural regulation of murine colonic motility was investigated. Norepinephrine (NE), via α1A ARs, activated a small conductance Ca2+ -activated K+ (SK) conductance, evoked outward currents and hyperpolarized PDGFRα+ cells (the α1A AR-SK channel signal pathway). α1 AR agonists increased intracellular Ca2+ transients in PDGFRα+ cells and inhibited spontaneous phasic contractions (SPCs) of colonic muscle through activation of a SK conductance. Sympathetic nerve stimulation inhibited both contractions of distal colon and propulsive contractions represented by the colonic migrating motor complexes (CMMCs) via the α1A AR-SK channel signal pathway. Postsynaptic signaling through α1A ARs in PDGFRα+ cells is a novel mechanism that conveys part of stress responses in the colon. PDGFRα+ cells appear to be a primary effector of sympathetic neural regulation of murine colonic motility.
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Affiliation(s)
- Masaaki Kurahashi
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Yoshihiko Kito
- Department of Pharmacology, Saga University, Saga, Japan
| | - Salah A Baker
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Libby K Jennings
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - James G R Dowers
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Sang Don Koh
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Kenton M Sanders
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
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29
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Agrawal L, Korkutata M, Vimal SK, Yadav MK, Bhattacharyya S, Shiga T. Therapeutic potential of serotonin 4 receptor for chronic depression and its associated comorbidity in the gut. Neuropharmacology 2020; 166:107969. [PMID: 31982703 DOI: 10.1016/j.neuropharm.2020.107969] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 01/14/2020] [Accepted: 01/16/2020] [Indexed: 12/19/2022]
Abstract
The latest estimates from world health organization suggest that more than 450 million people are suffering from depression and other psychiatric conditions. Of these, 50-60% have been reported to have progression of gut diseases. In the last two decades, researchers introduced incipient physiological roles for serotonin (5-HT) receptors (5-HTRs), suggesting their importance as a potential pharmacological target in various psychiatric and gut diseases. A growing body of evidence suggests that 5-HT systems affect the brain-gut axis in depressive patients, which leads to gut comorbidity. Recently, preclinical trials of 5-HT4R agonists and antagonists were promising as antipsychotic and prokinetic agents. In the current review, we address the possible pharmacological role and contribution of 5-HT4R in the pathophysiology of chronic depression and associated gut abnormalities. Physiologically, during depression episodes, centers of the sympathetic and parasympathetic nervous system couple together with neuroendocrine systems to alter the function of hypothalamic-pituitary-adrenal (HPA) axis and enteric nervous system (ENS), which in turn leads to onset of gastrointestinal tract (GIT) disorders. Consecutively, the ENS governs a broad spectrum of physiological activities of gut, such as visceral pain and motility. During the stages of emotional stress, hyperactivity of the HPA axis alters the ENS response to physiological and noxious stimuli. Consecutively, stress-induced flare, swelling, hyperalgesia and altered reflexes in gut eventually lead to GIT disorders. In summary, the current review provides prospective information about the role and mechanism of 5-HT4R-based therapeutics for the treatment of depressive disorder and possible consequences for the gut via brain-gut axis interactions. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.
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Affiliation(s)
- Lokesh Agrawal
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, 305-8577, Tennodai, Tsukuba, Ibaraki, Japan.
| | - Mustafa Korkutata
- Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA
| | - Sunil Kumar Vimal
- Department of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, PR China
| | - Manoj Kumar Yadav
- School of Integrative and Global Majors, University of Tsukuba, 1-1-1, 305-8577, Tennodai, Tsukuba, Ibaraki, Japan; Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Sanjib Bhattacharyya
- Department of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, PR China
| | - Takashi Shiga
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, 305-8577, Tennodai, Tsukuba, Ibaraki, Japan; Department of Neurobiology, Faculty of Medicine, University of Tsukuba,1-1-1, Tennodai, Tsukuba, 305-8577, Ibaraki, Japan.
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30
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Sarkar S, Choudhury S, Balasundaram S, Balasubramanian SP. Depression and anxiety associated with functional bowel disorders and its impact on quality of life: A cross-sectional study. Ind Psychiatry J 2020; 29:68-75. [PMID: 33776278 PMCID: PMC7989463 DOI: 10.4103/ipj.ipj_59_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 04/22/2020] [Accepted: 07/24/2020] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Functional bowel disorder (FBD) is conceptualized as a "biopsychosocial disorder." Psychological factors are important moderators of symptom severity and persistence, treatment seeking and response to treatment. We investigated psychological factors and quality of life (QOL) in patients with FBD. METHODS Seventy patients visiting the department of medical gastroenterology diagnosed as FBD were included in the study. Severity of FBD was rated with FBD Severity Index. The Depression, Anxiety, and Stress Scale was applied and patients were divided into two groups, i.e., with moderate stress (Group A) and with severe stress (Group B). QOL in both the groups was assessed by WHOQOL-BREF Scale. Chi-square, t-test was done to compare the groups. Regression analysis was done to find predictors of poor QOL. P < 0.05 was taken as significant. RESULTS Patients of Group B had a longer duration of illness and had higher prevalence of depressive disorder (P = 0.03) in comparison to patients in Group A, who had higher prevalence of anxiety disorders (P = 0.06). Severity of FBD was positively correlated with depression (r = 0.8; P = 0.02). Physical and psychological QOL was significantly impaired in Group B patients having depression (P = 0.02; P = 0.03). Regression analysis showed a positive trend for presence of depressive disorder (P = 0.05), anxiety disorder (P = 0.08) and severity of FBD (P = 0.09) as predictors of poor QOL. CONCLUSION In our study, the high prevalence of stress, anxiety and depression in patients with FBD indicates the need for routine screening of such symptoms along with a collaborative and holistic treatment approach. Several etiological perspectives explaining the complex gut-brain interaction are also provided.
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Affiliation(s)
- Sukanto Sarkar
- Department of Psychiatry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
| | - Sunayana Choudhury
- Department of Psychiatry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
| | - Sivaprakash Balasundaram
- Department of Psychiatry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
| | - SajeethManikanda Prabu Balasubramanian
- Department of Medical Gastroenterology Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
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31
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Mahurkar-Joshi S, Chang L. Epigenetic Mechanisms in Irritable Bowel Syndrome. Front Psychiatry 2020; 11:805. [PMID: 32922317 PMCID: PMC7456856 DOI: 10.3389/fpsyt.2020.00805] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 07/27/2020] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a brain-gut axis disorder characterized by abdominal pain and altered bowel habits. IBS is a multifactorial, stress-sensitive disorder with evidence for familial clustering attributed to genetic or shared environmental factors. However, there are weak genetic associations reported with IBS and a lack of evidence to suggest that major genetic factor(s) contribute to IBS pathophysiology. Studies on animal models of stress, including early life stress, suggest a role for environmental factors, specifically, stress associated with dysregulation of corticotropin releasing factor and hypothalamus-pituitary-adrenal (HPA) axis pathways in the pathophysiology of IBS. Recent evidence suggests that epigenetic mechanisms, which constitute molecular changes not driven by a change in gene sequence, can mediate environmental effects on central and peripheral function. Epigenetic alterations including DNA methylation changes, histone modifications, and differential expression of non-coding RNAs (microRNA [miRNA] and long non-coding RNA) have been associated with several diseases. The objective of this review is to elucidate the molecular factors in the pathophysiology of IBS with an emphasis on epigenetic mechanisms. Emerging evidence for epigenetic changes in IBS includes changes in DNA methylation in animal models of IBS and patients with IBS, and various miRNAs that have been associated with IBS and endophenotypes, such as increased visceral sensitivity and intestinal permeability. DNA methylation, in particular, is an emerging field in the realm of complex diseases and a promising mechanism which can provide important insights into IBS pathogenesis and identify potential targets for treatment.
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Affiliation(s)
- Swapna Mahurkar-Joshi
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine at UCLA, Los Angeles, CA, United States
| | - Lin Chang
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine at UCLA, Los Angeles, CA, United States
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Icenhour A, Labrenz F, Roderigo T, Benson S, Elsenbruch S. The Role of Chronic Stress in Normal Visceroception: Insights From an Experimental Visceral Pain Study in Healthy Volunteers. Front Psychiatry 2020; 11:107. [PMID: 32194454 PMCID: PMC7062678 DOI: 10.3389/fpsyt.2020.00107] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/07/2020] [Indexed: 12/12/2022] Open
Abstract
Visceroception is a complex phenomenon comprising the sensation, interpretation, and integration of sensations along the gut-brain axis, including pain or defecatory urgency. Stress is considered a crucial risk factor for the development and maintenance of disorders of gut-brain signaling, which are characterized by altered visceroception. Although the broad role of stress and stress mediators in disturbed visceroception is widely acknowledged, the putative contribution of chronic stress to variations in normal visceroception remains incompletely understood. We aimed to elucidate the role of chronic stress in shaping different facets of visceroception. From a well-characterized, large sample of healthy men and women (N = 180, 50% female), volunteers presenting with low (n = 57) and elevated (n = 61) perceived chronic stress were identified based on the validated Trier Inventory for Chronic Stress (TICS). Visceral sensitivity together with perceived and recalled intensity and defecatory urgency induced by repeated rectal distensions was experimentally assessed, and compared between low and elevated stress groups. Subgroups were compared regarding state anxiety and salivary cortisol concentrations across experimental phases and with respect to psychological measures. Finally, in the full sample and in chronic stress subgroups, a recall bias in terms of a discrepancy between the perception of experimentally-induced symptoms and their recall was tested. Participants with elevated chronic stress presented with increased state anxiety and higher cortisol concentrations throughout the experimental phases compared to the group with low chronic stress. Group differences in visceral sensitivity were not evident. The elevated stress group perceived significantly higher urgency during the stimulation phase, and recalled substantially higher feelings of urgency induced by rectal distensions, while perceived and recalled intensity were comparable between groups. Volunteers with elevated stress exhibited a recall bias in terms of a higher recall relative to mean perception of urgency, whereas no such bias was observed for the intensity of experimental visceral stimulation. Our findings in healthy men and women provide first evidence that the troublesome symptom of urgency might be particularly modifiable by chronic stress and support the relevance of memory biases in visceroception. These results may help to disentangle the impact of chronic stress on altered visceroception in disturbances of gut-brain communication.
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Affiliation(s)
- Adriane Icenhour
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Franziska Labrenz
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Till Roderigo
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sven Benson
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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33
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Labanski A, Langhorst J, Engler H, Elsenbruch S. Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology 2020; 111:104501. [PMID: 31715444 DOI: 10.1016/j.psyneuen.2019.104501] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 10/17/2019] [Accepted: 10/29/2019] [Indexed: 12/18/2022]
Abstract
The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. These include the functional gastrointestinal disorders (FGID), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn's disease. Although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (PNE)/ psychoneuroimmunology (PNI) remain only loosely connected. We aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. To this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of FGIDs and IBD. From an interdisciplinary PNE/PNI perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of FGID and IBD. We provide an overview of evidence regarding non-pharmacological treatment approaches that target central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.
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Affiliation(s)
- Alexandra Labanski
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Jost Langhorst
- Chair for Integrative Medicine, University of Duisburg-Essen, Essen, Germany; Clinic for Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany
| | - Harald Engler
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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34
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Mao CP, Chen FR, Sun HH, Shi MJ, Yang HJ, Li XH, Ding D. Larger regional volume of the thalamus in diarrhea-predominant irritable bowel syndrome: a cross-sectional study. Brain Imaging Behav 2019; 14:2302-2310. [PMID: 31468373 DOI: 10.1007/s11682-019-00181-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction in patients with irritable bowel syndrome (IBS). However, the regional morphological alterations of the thalamus in IBS are not well defined. We acquired structural magnetic resonance data from 34 patients with IBS and 34 demographically similar healthy subjects. Data processing was performed using FMRIB's Integrated Registration and Segmentation Tool (FIRST). Volumetric analysis and surface-based vertex analysis were both carried out to characterize the morphology of the thalamus and other subcortical structures. Our results suggested that the majority (31 cases) of the patients with IBS had diarrhea-predominant symptoms. Volumetric analysis revealed a larger normalized volume of the right thalamus and left caudate nucleus in patients with IBS than in healthy controls. Surface analysis indicated that the difference arose mainly from the laterodorsal nucleus of the right thalamus, and the body of the left caudate nucleus. In addition, patients with IBS had different hemispheric asymmetries of the thalamus (rightward) and caudate nucleus (leftward) from controls (leftward for the thalamus and rightward for the caudate nucleus). In general, our results indicated that patients with diarrhea-predominant IBS had enlarged thalamus and caudate nucleus volumes, as well as altered hemispheric asymmetries of these two structures, compared with healthy controls. The neuroimaging evidence of these structural alterations helps clarify the underlying pathophysiology of diarrhea-predominant IBS.
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Affiliation(s)
- Cui Ping Mao
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, 710004, Xi'an, Shaanxi, People's Republic of China.
| | - Fen Rong Chen
- Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, Xi'an, Shaanxi, People's Republic of China
| | - Hong Hong Sun
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, 710004, Xi'an, Shaanxi, People's Republic of China.
| | - Mei Juan Shi
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, 710004, Xi'an, Shaanxi, People's Republic of China
| | - Hua Juan Yang
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, 710004, Xi'an, Shaanxi, People's Republic of China
| | - Xiao Hui Li
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, 710004, Xi'an, Shaanxi, People's Republic of China
| | - Dun Ding
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, 157, Xiwu Road, 710004, Xi'an, Shaanxi, People's Republic of China
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Botschuijver S, van Diest SA, van Thiel IAM, Saia RS, Strik AS, Yu Z, Maria-Ferreira D, Welting O, Keszthelyi D, Jennings G, Heinsbroek SEM, Elferink RPO, Schuren FHJ, de Jonge WJ, van den Wijngaard RM. Miltefosine treatment reduces visceral hypersensitivity in a rat model for irritable bowel syndrome via multiple mechanisms. Sci Rep 2019; 9:12530. [PMID: 31467355 PMCID: PMC6715706 DOI: 10.1038/s41598-019-49096-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 08/02/2019] [Indexed: 12/17/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a heterogenic, functional gastrointestinal disorder of the gut-brain axis characterized by altered bowel habit and abdominal pain. Preclinical and clinical results suggested that, in part of these patients, pain may result from fungal induced release of mast cell derived histamine, subsequent activation of sensory afferent expressed histamine-1 receptors and related sensitization of the nociceptive transient reporter potential channel V1 (TRPV1)-ion channel. TRPV1 gating properties are regulated in lipid rafts. Miltefosine, an approved drug for the treatment of visceral Leishmaniasis, has fungicidal effects and is a known lipid raft modulator. We anticipated that miltefosine may act on different mechanistic levels of fungal-induced abdominal pain and may be repurposed to IBS. In the IBS-like rat model of maternal separation we assessed the visceromotor response to colonic distension as indirect readout for abdominal pain. Miltefosine reversed post-stress hypersensitivity to distension (i.e. visceral hypersensitivity) and this was associated with differences in the fungal microbiome (i.e. mycobiome). In vitro investigations confirmed fungicidal effects of miltefosine. In addition, miltefosine reduced the effect of TRPV1 activation in TRPV1-transfected cells and prevented TRPV1-dependent visceral hypersensitivity induced by intracolonic-capsaicin in rat. Miltefosine may be an attractive drug to treat abdominal pain in IBS.
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Affiliation(s)
- Sara Botschuijver
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Sophie A van Diest
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Isabelle A M van Thiel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Rafael S Saia
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Anne S Strik
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Zhumei Yu
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Department of Neurobiology, Tongji Medical College, HUST, Wuhan, People's Republic of China.,State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Daniele Maria-Ferreira
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil
| | - Olaf Welting
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Gary Jennings
- Business Development, Redivia, Technische Universität, Dresden, Germany
| | - Sigrid E M Heinsbroek
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Ronald P Oude Elferink
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Frank H J Schuren
- Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, The Netherlands
| | - Wouter J de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - René M van den Wijngaard
- Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands. .,Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
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36
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Muthyala A, Feuerhak KJ, Harmsen WS, Chakraborty S, Bailey KR, Bharucha AE. Effects of psychosensory stimulation on anal pressures: Effects of alfuzosin. Neurogastroenterol Motil 2019; 31:e13618. [PMID: 31032543 PMCID: PMC6559834 DOI: 10.1111/nmo.13618] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 04/15/2019] [Accepted: 04/17/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Our aim is to explain the lack of clarity in the ways in which anxiety and depression, which are common in defecatory disorders (DD), may contribute to the disorder. In this study, we evaluate the effects of mental stress and relaxation on anal pressures and the mechanisms thereof. METHODS In 38 healthy women and 36 DD patients, rectoanal pressures were assessed at rest and during mental stressors (ie, word-color conflict [Stroop] and mental arithmetic tests) and mental relaxation, before and after randomization to placebo or the adrenergic α1 -antagonist alfuzosin. KEY RESULTS During the baseline Stroop test, the anal pressure increased by 6 ± 13 mm Hg (mean ± SD, P = 0.004) in healthy women and 9 ± 10 mm Hg (P = 0.0001) in constipated women. During mental arithmetic, the anal pressure increased in healthy (4 ± 8 mm Hg, P = 0.002) and constipated women (5 ± 9 mm Hg, P = 0.004). After relaxation, anal pressure declined (P = 0.0004) by 3 ± 4 mm Hg in DD patients but not in controls. Alfuzosin reduced (P = 0.0001) anal resting pressure (by 31 ± 19 mm Hg) vs placebo (16 ± 18 mm Hg). However, during the postdrug Stroop test, anal pressure increased (P = 0.0001) in participants who received alfuzosin but not placebo. CONCLUSIONS & INFERENCES In healthy controls and DD patients, mental stressors likely increased anal pressure by contracting the internal anal sphincter; relaxation reduced anal pressure in DD patients. Alfuzosin reduced anal resting pressure but did not block the Stroop-mediated contractile response, which suggests that this response is not entirely mediated by adrenergic α1 receptors.
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Affiliation(s)
- Anjani Muthyala
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology
| | - Kelly J. Feuerhak
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology
| | - William S. Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Subhankar Chakraborty
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology
| | - Kent R. Bailey
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Adil E. Bharucha
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology
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Hellström PM. Pathophysiology of the irritable bowel syndrome - Reflections of today. Best Pract Res Clin Gastroenterol 2019; 40-41:101620. [PMID: 31594651 DOI: 10.1016/j.bpg.2019.05.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 05/23/2019] [Indexed: 01/31/2023]
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal symptom complex defined by abdominal pain and disturbed bowel habits over 3 months within a period of 6 months, in absence of any identifiable organic pathology. Over the years, speculations of the pathophysiology of IBS has moved from elusive central nervous symptoms impinging on psychosomatic disease, to objective signs of intestinal fermentation with abdominal bloating and intestinal dysmotility. The specific subgroup of post-infectious IBS is of special interest since it opens the possibility of dysbiosis as the pivotal point for development of IBS in association with traveler's diarrhea or antibiotic treatment with ensuing dysbiosis and abdominal symptoms that may resolve over decades. The undefined disease mechanisms that take place within the gut seem responsible for the gut-brain signaling leading to activation of brain centers that drive the clinical picture of IBS, further modulated by the patient's social background and previous lifetime events.
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Affiliation(s)
- Per M Hellström
- Department of Medical Sciences, Gastroenterology Unit, Uppsala University, Bldg 40, 5th Floor, SE-75185, Uppsala, Sweden.
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38
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Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women. Pain 2019; 160:1719-1728. [DOI: 10.1097/j.pain.0000000000001579] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Activation of Peripheral Blood CD4+ T-Cells in IBS is not Associated with Gastrointestinal or Psychological Symptoms. Sci Rep 2019; 9:3710. [PMID: 30842618 PMCID: PMC6403230 DOI: 10.1038/s41598-019-40124-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 02/08/2019] [Indexed: 02/07/2023] Open
Abstract
Immune activation may underlie the pathogenesis of irritable bowel syndrome (IBS), but the evidence is conflicting. We examined whether peripheral CD4+ T-cells from IBS patients demonstrated immune activation and changes in cytokine production. To gain mechanistic insight, we examined whether immune activation correlated with psychological stress and changing symptoms over time. IBS patients (n = 29) and healthy volunteers (HV; n = 29) completed symptom and psychological questionnaires. IBS patients had a significant increase in CD4+ T-cells expressing the gut homing marker integrin β7 (p = 0.023) and lymphoid marker CD62L (p = 0.026) compared to HV. Furthermore, phytohaemagglutinin stimulated CD4+ T-cells from IBS-D patients demonstrated increased TNFα secretion when compared to HV (p = 0.044). Increased psychological scores in IBS did not correlate with TNFα production, while stress hormones inhibited cytokine secretion from CD4+ T-cells of HV in vitro. IBS symptoms, but not markers of immune activation, decreased over time. CD4+ T-cells from IBS-D patients exhibit immune activation, but this did not appear to correlate with psychological stress measurements or changing symptoms over time. This could suggest that immune activation is a surrogate of an initial trigger and/or ongoing parallel peripheral mechanisms.
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40
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Fani M, Mostamand J, Fani M, Chitsaz N, Feizi A. The effect of aerobic exercises among women with mild and moderate irritable bowel syndrome: A pilot study. J Bodyw Mov Ther 2019; 23:161-165. [DOI: 10.1016/j.jbmt.2018.02.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 01/19/2018] [Accepted: 01/30/2018] [Indexed: 12/14/2022]
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Rangan V, Mitsuhashi S, Singh P, Ballou S, Hirsch W, Sommers T, Nee J, Iturrino J, Lembo A. Risk Factors for Fecal Urgency Among Individuals With and Without Diarrhea, Based on Data From the National Health and Nutrition Examination Survey. Clin Gastroenterol Hepatol 2018; 16:1450-1458.e2. [PMID: 29474972 PMCID: PMC6098738 DOI: 10.1016/j.cgh.2018.02.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 01/25/2018] [Accepted: 02/11/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Fecal urgency is a common symptom among patients with gastrointestinal disorders, but can also occur in healthy individuals with normal bowel habits. There have been few studies of fecal urgency in the general population. We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) to analyze the prevalence of and risk factors for this symptom. METHODS We analyzed data from 4676 persons who completed the Bowel Health Questionnaire from the NHANES, from 2009 through 2010. The NHANES sampled a nationally representative group of adults in the United States and provides information on demographics, medical comorbidities, and dietary habits of survey participants. The Bowel Health Questionnaire provided additional information about bowel symptoms such as urgency, incontinence, constipation, and diarrhea. We identified individuals with fecal urgency and calculated differences in fecal urgency among subgroups using chi-squared analysis. We used logistic regression to identify factors associated with urgency. RESULTS In our study population, the prevalence of fecal urgency was 3.3%; 29.5% of individuals with fecal urgency had diarrhea. The prevalence of fecal urgency was significantly higher in individuals who had diarrhea (14.8%) than in individuals without diarrhea (3.1%). Older age, female sex, poverty, urinary urge incontinence, diarrhea, and increased stool frequency were all associated with fecal urgency on multivariable analysis. Decreased fiber intake and increased carbohydrate intake were associated with urgency among individuals with diarrhea. CONCLUSIONS In an analysis of data from 4676 individuals who completed a Bowel Health Questionnaire from the NHANES, we found a significantly higher proportion of individuals with diarrhea to have fecal urgency. However, most individuals with fecal urgency do not have diarrhea. Factors associated with fecal urgency vary among individuals with and without diarrhea.
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Affiliation(s)
- Vikram Rangan
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Shuji Mitsuhashi
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Prashant Singh
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Sarah Ballou
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - William Hirsch
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Thomas Sommers
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Judy Nee
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Johanna Iturrino
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Anthony Lembo
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
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42
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Polster A, Friberg P, Gunterberg V, Öhman L, Le Nevé B, Törnblom H, Cvijovic M, Simren M. Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms. Neurogastroenterol Motil 2018; 30:e13320. [PMID: 29575352 DOI: 10.1111/nmo.13320] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 01/29/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Disturbed brain-gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain-gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms. METHODS Heart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24-hour period). Frequency (5 minutes, supine, standing) and time domains (24 hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS-DA)). KEY RESULTS We analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P < .01). A subset of patients (n = 30; 19%) with an aberrant global HRV profile was identified through PCA and OPLS-DA; these patients reported more severe symptoms of frequent (P < .05) and loose stools (P = .03), as well as urgency (P = .01). CONCLUSIONS AND INFERENCES Altered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.
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Affiliation(s)
- A Polster
- Department of Internal Medicine and Clinical Nutrition, Sahlgrenska University Hospital, Göteborg, Sweden
| | - P Friberg
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
| | - V Gunterberg
- Department of Internal Medicine and Clinical Nutrition, Sahlgrenska University Hospital, Göteborg, Sweden
| | - L Öhman
- Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - B Le Nevé
- Danone Nutricia Research, Palaiseau, France
| | - H Törnblom
- Department of Internal Medicine and Clinical Nutrition, Sahlgrenska University Hospital, Göteborg, Sweden
| | - M Cvijovic
- Department of Mathematical Sciences, Chalmers University of Technology and Göteborg University, Göteborg, Sweden
| | - M Simren
- Department of Internal Medicine and Clinical Nutrition, Sahlgrenska University Hospital, Göteborg, Sweden.,Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Effects of acute psychological stress on placebo and nocebo responses in a clinically relevant model of visceroception. Pain 2018; 158:1489-1498. [PMID: 28471874 DOI: 10.1097/j.pain.0000000000000940] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Participants then underwent the Trier Social Stress Test (N = 60) or a simple cognitive task (control, N = 60) and were randomized to positive (placebo), negative (nocebo), or neutral treatment information regarding intravenous administration of saline. The series of distensions was repeated, and changes in visual analogue scales from BASELINE to TEST were compared between groups using analysis of covariance and planned post hoc tests. Treatment information emerged as a main factor (P <0.001), supporting treatment information effects for both urgency and pain. Effects for urgency were modulated by stress (interaction effect: P <0.05): Positive information reduced urgency (P = 0.025), while negative information increased urgency (P = 0.026) only in stressed groups. For pain, effects of stress emerged for nocebo responses, which were only evident in stressed groups (P = 0.009). This is the first experimental study supporting effects of acute psychological stress on placebo and nocebo responses in visceroception. Results call for mechanistic as well as patient studies to assess how psychological stress shapes patients' treatment expectations and thereby affects health outcomes.
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Bradley S, Alderson S, Ford AC, Foy R. General practitioners' perceptions of irritable bowel syndrome: a Q-methodological study. Fam Pract 2018; 35:74-79. [PMID: 28985313 DOI: 10.1093/fampra/cmx053] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common disorder that imposes a significant burden upon societies, health care and quality of life, worldwide. While a diverse range of patient viewpoints on IBS have been explored, the opinions of the GPs they ideally need to develop therapeutic partnerships with are less well defined. OBJECTIVE To explore how GPs perceive IBS, using Q-methodology, which allows quantitative interpretation of qualitative data. DESIGN AND SETTING A Q-methodological study of GPs in Leeds, UK. METHOD Thirty-three GPs completed an online Q-sort in which they ranked their level of agreement with 66 statements. Factor analysis of the Q-sorts was performed to determine the accounts that predominated in understandings of IBS. Ten of the GPs were interviewed in person and responses to the statements recorded to help explain the accounts. RESULTS Analysis yielded one predominant account shared by all GPs-that IBS was a largely psychological disorder. This account overshadowed a debate represented by a minority, polarized between those who viewed IBS as almost exclusively psychological, versus those who believed IBS had an organic basis, with a psychological component. The overwhelming similarity in responses indicates that all GPs shared a common perspective on IBS. Interviews suggested degrees of uncertainty and discomfort around the aetiology of IBS. CONCLUSION There was overwhelming agreement in the way GPs perceived IBS. This contrasts with the range of patient accounts of IBS and may explain why both GPs and their patients face difficult negotiations in achieving therapeutic relationships.
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Affiliation(s)
- Stephen Bradley
- Academic Unit of Primary Care, University of Leeds, Leeds, UK
| | - Sarah Alderson
- Academic Unit of Primary Care, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.,Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Robbie Foy
- Academic Unit of Primary Care, University of Leeds, Leeds, UK
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Abstract
More than eighty years after Hans Selye (1907-1982) first developed a concept describing how different types of environmental stressors affect physiological functions and promote disease development (called the "general adaptation syndrome") in 1936, we herein review advances in theoretical, mechanistic, and clinical knowledge in stress research, especially in the area of gastroenterology, and summarize progress and future perspectives arising from an interdisciplinary psychoneurobiological framework in which genetics, epigenetics, and other advanced ( omics) technologies in the last decade continue to refine knowledge about how stress affects the brain-gut axis in health and gastrointestinal disease. We demonstrate that neurobiological stress research continues to be a driving force for scientific progress in gastroenterology and related clinical areas, inspiring translational research from animal models to clinical applications, while highlighting some areas that remain incompletely understood, such as the roles of sex/gender and gut microbiota in health and disease. Future directions of research should include not only the genetics of the stress response and resilience but also epigenetic contributions.
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Affiliation(s)
- Sigrid Elsenbruch
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Paul Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
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Agostini A, Ballotta D, Righi S, Moretti M, Bertani A, Scarcelli A, Sartini A, Ercolani M, Nichelli P, Campieri M, Benuzzi F. Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study. Neurogastroenterol Motil 2017; 29:1-10. [PMID: 28560758 DOI: 10.1111/nmo.13108] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 04/17/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. METHODS 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. KEY RESULTS Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). CONCLUSIONS & INFERENCES The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity.
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Affiliation(s)
- A Agostini
- Department of Experimental, Diagnostic, and Specialty Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.,Department of Psychology, University of Bologna, Bologna, Italy
| | - D Ballotta
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - S Righi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - M Moretti
- Department of Experimental, Diagnostic, and Specialty Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - A Bertani
- Department of Gastroenterology, IBD Unit, Policlinico Hospital, Modena, Italy
| | - A Scarcelli
- Department of Gastroenterology, IBD Unit, Policlinico Hospital, Modena, Italy
| | - A Sartini
- Department of Gastroenterology, IBD Unit, Policlinico Hospital, Modena, Italy
| | - M Ercolani
- Department of Experimental, Diagnostic, and Specialty Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.,Department of Psychology, University of Bologna, Bologna, Italy
| | - P Nichelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - M Campieri
- Department of Clinical Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - F Benuzzi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
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Kim HM, Youn CH, Ko HJ, Lee SH, Lee YM. The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms. Korean J Fam Med 2017; 38:233-238. [PMID: 28775815 PMCID: PMC5541173 DOI: 10.4082/kjfm.2017.38.4.233] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 09/01/2016] [Indexed: 01/14/2023] Open
Abstract
Background Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to uncover the effects of POPs on the endocrine and nervous systems and on cancer, few focus on the relationship between low-dose POPs and public health. Here, we attempt to determine the relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation. Methods We recruited 121 subjects who visited Kyungpook National University Medical Center for health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls (PCBs) and 23 types of organochlorine pesticides (OCP). Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms. Results Based on our results, abdominal discomfort showed an inverse relationship with several PCBs and an inverted U-shaped relationship with several other OCPs including pp-DDD and pp-DDT. The effects of pp-DDD and pp-DDT on abdominal discomfort were similar to those of OCPs on obesity and metabolic syndrome. Conclusion Our results suggest that mild and unspecified gastrointestinal symptoms with no clear causes could be related to POP levels.
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Affiliation(s)
- Hyo-Min Kim
- Department of Family Medicine, Kyungpook National University Medical Center, Daegu, Korea
| | - Chang-Ho Youn
- Department of Family Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Hae Jin Ko
- Department of Family Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Seon-Hwa Lee
- Graduate School of Public Health, Kyungpook National University, Daegu, Korea
| | - Yu-Mi Lee
- Regional Cardiocerebrovascular Center, Kyungpook National University Hospital, Daegu, Korea
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Kinsinger SW. Cognitive-behavioral therapy for patients with irritable bowel syndrome: current insights. Psychol Res Behav Manag 2017; 10:231-237. [PMID: 28790872 PMCID: PMC5530860 DOI: 10.2147/prbm.s120817] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) condition associated with significant health care utilization and quality-of-life impairment. Latest research indicates that the brain-gut axis plays a key role in the disorder, and the presence of psychological factors and central processing deficits contribute to symptom severity and disability. Psychological therapies as a whole have demonstrated good efficacy in reducing the severity of IBS symptoms. Cognitive-behavioral therapy (CBT) has been tested most rigorously in multiple randomized controlled trials and consistently demonstrates significant and durable effects on IBS symptoms and quality of life. Various protocols for treating IBS have been developed, and most recent advances in the field include exposure-based treatments to target symptom-specific anxiety as well as modified delivery methods, including internet-based treatment models. Despite the well-documented advantages of CBT for IBS, it has been poorly disseminated and few patients have access to this treatment. The primary barrier to dissemination is the limited number of therapists with adequate training in GI psychology to provide this evidence-based intervention. Future developments in the field need to focus on training opportunities to equip more therapists to competently provide CBT for this population. Further efforts to develop telemedicine platforms for delivering this intervention will also improve accessibility for patients.
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Affiliation(s)
- Sarah W Kinsinger
- Behavioral Medicine for Digestive Health, Division of Gastroenterology and Nutrition, Loyola University Medical Center, Maywood, IL, USA
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Development of the Irritable Bowel Syndrome Cognitive Affective Scale: a brief self-report measure for clinical and research settings. Eur J Gastroenterol Hepatol 2017; 29:849-854. [PMID: 28338499 DOI: 10.1097/meg.0000000000000872] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Measures of cognitive-affective processes believed to underlie Irritable Bowel Syndrome (IBS) symptom expression are used widely in both clinical and research settings. When combined, these measures can be time-consuming and it is not clear whether they evaluate distinct or overlapping constructs. With this study, we seek to identify the most critical cognitive-affective components contributing toward the expression of IBS and to identify which items in these constructs might be streamlined into a single, brief self-report measure. PATIENTS AND METHODS This measure was developed according to Food and Drug Administration guidelines for patient-reported outcome development. First, authors consolidated existing cognitive-affective measures (visceral sensitivity, anxiety sensitivity, and pain catastrophization) into a single questionnaire. Second, a principal components factor analysis was carried out on the basis of responses from a sample of participants with IBS. Third, on the basis of the results of the factor analysis, items were reduced to the final brief self-report measure and preliminary validity/reliability analyses (Cronbach's α, correlation with other related constructs) were carried out. RESULTS An initial, 44-item measure was created. In all, 179 patients with ROME-III IBS completed an online survey. Principal component analysis and item reduction yielded a 15-item scale with three factors: pain catastrophization, visceral hypervigilance, and extraintestinal hypervigilance. The final three factors showed comparable internal consistencies (α>0.90), concurrent validity, and predictive validity compared with the original 44 items. CONCLUSION Although more research is warranted, the 15 items identified appear to provide an accurate measure of two important cognitive-affective constructs in the IBS population.
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50
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Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ. Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population-based study. Neurogastroenterol Motil 2017; 29:10.1111/nmo.13041. [PMID: 28256048 PMCID: PMC5730281 DOI: 10.1111/nmo.13041] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 01/09/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND It is unknown why functional gastrointestinal disorders (FGIDs) overlap and limited information exists on risk factors for those with overlap. Our aim was to estimate the prevalence of combinations of FGIDs including reflux (FGIDs-gastroesophageal reflux [GER]), and evaluate potential risk factors for people with multiple disorders in a representative US community. METHODS A population-based study was conducted by mailing a valid GI symptom questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN. Rome III definitions were used to identify people with FGIDs, and GER was defined by weekly or more frequent heartburn or acid regurgitation. The prevalence of people meeting multiple symptom complexes was estimated. Moreover, potential risk factors for people with multiple disorders were evaluated. KEY RESULTS A total of 3548 people provided data for each of the necessary symptom questions (mean age: 61±16 years, 54% female). Among these 3548 subjects, 2009 (57%) had no FGIDs-GER, 906 (26%) had a pure FGID-GER, 372 (10%) had 2 FGIDs-GER, and 261 (7%) had 3 or more FGIDs-GER. Somatization as assessed by a higher Somatic Symptom Checklist score (OR=3.3, 95% CI [2.7,4.1]) was associated with an increased odds for those with 3 or more FGIDs-GER compared to subjects with a pure FGID-GER adjusting for age and gender. CONCLUSIONS AND INFERENCES Symptom complex overlap is common rather than rare in the community. GER is an integral symptom complex associated with both upper and lower FGIDs. Somatization is a strong risk factor for multiple FGIDs.
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Affiliation(s)
- Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - G. Richard Locke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Cathy D. Schleck
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
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