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Zeraattalab-Motlagh S, Ranjbar M, Mohammadi H, Adibi P. Nutritional Interventions in Adult Patients With Irritable Bowel Syndrome: An Umbrella Review of Systematic Reviews and Meta-analyses of Randomized Clinical Trials. Nutr Rev 2025; 83:e1343-e1354. [PMID: 39110917 DOI: 10.1093/nutrit/nuae107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/14/2025] Open
Abstract
CONTEXT There is still debate regarding the effect of nutritional interventions in improving irritable bowel syndrome (IBS) symptoms. OBJECTIVES The aim was to examine the evidence certainty and validity of all existing meta-analyses of intervention trials on nutritional interventions in patients with IBS. DATA SOURCES Scopus, PubMed, and Web of Science were reviewed until June 2023. DATA EXTRACTION Meta-analyses assessing the impacts of nutritional interventions in adults with IBS were entered. Effect sizes of nutritional interventions were recalculated by applying a random-effects model. GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) was implemented to determine evidence certainty. RESULTS A total of 175 trials in 58 meta-analyses were entered describing the effects of 11 nutritional interventions on IBS-related outcomes. Nutritional interventions had beneficial effects on some IBS-related outcomes. For instance, soluble fiber, peppermint oil, and aloe vera improved IBS symptoms, and vitamin D3 and curcumin improved IBS symptom severity. Tongxieyaofang improved abdominal pain severity and stool frequency. Nevertheless, these outcomes have mainly shown small effects and low to very low evidence certainty. With regard to abdominal pain after probiotic supplementation (relative risk [RR]: 4.04; 95% confidence interval [CI]: 2.36, 6.92; GRADE = moderate) and IBS symptoms after a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (RR: 1.48; 95% CI: 1.14, 1.93; GRADE = moderate), there was evidence that probiotics and a low-FODMAP diet can confer clinical and favorable effects. CONCLUSION The current review does not support nutritional interventions for improving IBS symptoms. With regard to probiotics and a low-FODMAP diet, considering limitations like short-term study duration, there was an influential clinical impact. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42023429991.
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Affiliation(s)
| | - Mahsa Ranjbar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 1417613151, Iran
| | - Hamed Mohammadi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 1417613151, Iran
| | - Peyman Adibi
- Isfahan Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
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Black CJ, Ford AC. An evidence-based update on the diagnosis and management of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2025:1-16. [PMID: 39835671 DOI: 10.1080/17474124.2025.2455586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction affecting 5% of the population. The cardinal symptoms are abdominal pain and altered stool form or frequency. AREAS COVERED Diagnosis and management of IBS. We searched the literature for diagnostic accuracy studies, randomized controlled trials, and meta-analyses. A positive diagnosis of IBS, alongside testing to exclude celiac disease, is recommended. Exhaustive investigation has a low yield. Patients should be offered traditional dietary advice. If response is incomplete, specialist dietetic guidance should be considered. Probiotics may be beneficial, but quality of evidence is poor. First-line treatment of constipation is with laxatives, with secretagogues used where these are ineffective. Anti-diarrheal drugs should be used first-line for diarrhea, with second-line drugs including 5-hydroxytryptamine-3 antagonists, eluxadoline, or rifaximin, where available. First-line treatment of abdominal pain should be with antispasmodics, with gut-brain neuromodulators prescribed second-line. Low-dose tricyclic antidepressants, such as amitriptyline, are preferred. Brain-gut behavioral therapies are effective and have evidence for efficacy in patients refractory to standard therapies. EXPERT OPINION Despite substantial advances, there remains scope for improvement in terms of both the diagnosis and management of IBS. Reinforcement of positive diagnostic strategies for the condition and novel treatment paradigms are required.
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Affiliation(s)
- Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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Lenz FA, Dougherty PM, Meeker TJ, Saffer MI, Oishi K. Neuroscience of the human thalamus related to acute pain and chronic "thalamic" pain. J Neurophysiol 2024; 132:1756-1778. [PMID: 39412562 PMCID: PMC11687836 DOI: 10.1152/jn.00065.2024] [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: 02/16/2024] [Revised: 09/03/2024] [Accepted: 09/16/2024] [Indexed: 11/27/2024] Open
Abstract
The association of posterior thalamic strokes with the presence of chronic "thalamic" pain was described in the early 1900s and revisited in a recent review of these patients. Acute pain in corporal structures is associated with the spinothalamic tract (STT), which originates in the dorsal horn of the spinal cord, whereas that associated with cranial structures is associated with the spinal division of the trigeminal nucleus. These pathways terminate in the ventral posterior nucleus (VP), including its posterior and inferior subnuclei and its core, which is classically associated with tactile and haptic functions. In medial nuclei (medial dorsal and intralaminar) receptive fields are large and stimulation evokes diffuse unpleasant sensations and pain while neurons in these nuclei subserve cognitive processes of attention, alerting, and conditioning. In the lateral nuclei neurons have small receptive and projected fields and high resolution of responses to somatic stimuli. Neurons in the lateral nuclei respond to stimuli producing pain, temperature, and visceral sensations while stimulation evokes similar sensations. Small strokes in VP core versus structures located inferior and posterior are associated with thalamic pain and decreased tactile, painful, and cold sensations and with decreased evoked potentials for painful (laser) heat and median nerve stimulation (electrical). Lesions of VP, but not ventral medial posterior nucleus (VMpo), are associated with thalamic pain, contrary to the recent "disinhibition" model. We review the evidence that the lateral nuclei are associated with multiple processes including tactile, nociceptive, visceral, and thermal content of stimuli, whereas the medial nuclei are related to cognitions about those stimuli.
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Affiliation(s)
- Fred A Lenz
- Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, United States
| | - Pat M Dougherty
- Department of Pain Medicine, MD Anderson Cancer Center, Houston, Texas, United States
| | - Timothy J Meeker
- Department of Biology, Morgan State University, Baltimore, Maryland, United States
| | - Mark I Saffer
- Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, United States
| | - Kenichi Oishi
- Department of Radiology, Radiological Science, and Neurology, Johns Hopkins University, Baltimore, Maryland, United States
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Han L, Xu Q, Meng P, Xu R, Nan J. Brain identification of IBS patients based on GBDT and multiple imaging techniques. Phys Eng Sci Med 2024; 47:651-662. [PMID: 38416373 DOI: 10.1007/s13246-024-01394-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 01/16/2024] [Indexed: 02/29/2024]
Abstract
The brain biomarker of irritable bowel syndrome (IBS) patients is still lacking. The study aims to explore a new technology studying the brain alterations of IBS patients based on multi-source brain data. In the study, a decision-level fusion method based on gradient boosting decision tree (GBDT) was proposed. Next, 100 healthy subjects were used to validate the effectiveness of the method. Finally, the identification of brain alterations and the pain evaluation in IBS patients were carried out by the fusion method based on the resting-state fMRI and DWI for 46 patients and 46 controls selected randomly from 100 healthy subjects. The results showed that the method can achieve good classification between IBS patients and controls (accuracy = 95%) and pain evaluation of IBS patients (mean absolute error = 0.1977). Moreover, both the gain-based and the permutation-based evaluation instead of statistical analysis showed that left cingulum bundle contributed most significantly to the classification, and right precuneus contributed most significantly to the evaluation of abdominal pain intensity in the IBS patients. The differences seem to suggest a probable but unexplored separation about the central regions between the identification and progression of IBS. This finding may provide one new thought and technology for brain alteration related to IBS.
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Affiliation(s)
- Li Han
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, 136 Science Avenue, Zhengzhou, 450000, Henan, China
| | - Qian Xu
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, 136 Science Avenue, Zhengzhou, 450000, Henan, China
| | - Panting Meng
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, 136 Science Avenue, Zhengzhou, 450000, Henan, China
| | - Ruyun Xu
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, 136 Science Avenue, Zhengzhou, 450000, Henan, China
| | - Jiaofen Nan
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, 136 Science Avenue, Zhengzhou, 450000, Henan, China.
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Xu Z, Ning F, Zhang X, Wang Q, Zhang Y, Guo Y, Jia H. Deciphering the brain-gut axis: elucidating the link between cerebral cortex structures and functional gastrointestinal disorders via integrated Mendelian randomization. Front Neurosci 2024; 18:1398412. [PMID: 38841096 PMCID: PMC11152161 DOI: 10.3389/fnins.2024.1398412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 04/30/2024] [Indexed: 06/07/2024] Open
Abstract
Background Observational studies have suggested associations between functional gastrointestinal disorders (FGIDs) and variations in the cerebral cortex. However, the causality of these relationships remains unclear, confounded by anxiety and depression. To clarify these causal relationships and explore the mediating roles of anxiety and depression, we applied univariate, multivariable, and mediation Mendelian randomization (MR) analyses. Method We utilized genome-wide association study (GWAS) summary data from the FinnGen database and the ENIGMA consortium, identifying genetic variants associated with irritable bowel syndrome (IBS), functional dyspepsia (FD), and cerebral cortex structures. Data on anxiety and depression came from FinnGen and a large meta-analysis. Utilizing a bidirectional univariate MR approach, we explored correlations between FD, IBS, and cortex variations. Then, independent effects were assessed through multivariable MR. A meta-analysis of these results, incorporating data from two cohorts, aimed to increase precision. We also explored the potential mediating roles of anxiety and depression. Results Our findings indicate a negative causal correlation between FD and the thickness of the rostral anterior cingulate cortex (rACC) across both global and regional adjustments (β = -0.142, 95% confidence interval (CI): -0.209 to-0.074, P.FDR = 0.004; β = -0.112, 95%CI: -0.163 to-0.006, P.FDR = 0.003) and a positive causal correlation with the globally adjusted thickness of the superior frontal gyrus (SFG) (β = 0.107, 95%CI: 0.062 to 0.153, P.FDR = 0.001). The causal correlation with the rACC persisted after multiple variable adjustments (β = -0.137, 95% CI: -0.187 to-0.087, P.FDR = 1.81 × 10-5; β = -0.109, 95%CI: -0.158 to-0.06, P.FDR = 0.002). A significant causal association was found between globally adjusted surface area of the caudal anterior cingulate cortex (cACC) and IBS (odds ratio = 1.267, 95%CI: 1.128 to 1.424, P.FDR = 0.02). The analysis showed that neither anxiety nor depression mediated the relationship between FGIDs and cerebral cortex structures. Conclusion Our research provides significant MR evidence of a bidirectional causal relationship between FGIDs and the cerebral cortex structures. This evidence not only confirms the two-way communication along the brain-gut axis but also illuminates the underlying pathophysiology, paving the way for identifying potential therapeutic approaches.
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Affiliation(s)
- Zhiwei Xu
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Fenglan Ning
- Department of Acupuncture and Rehabilitation, Longkou Traditional Chinese Medicine Hospital, Yantai, Shandong, China
| | - Xuecheng Zhang
- Department of Proctology, China-Japan Friendship Hospital, Beijing, China
| | - Qi Wang
- Department of Acupuncture, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Yimei Zhang
- Department of Acupuncture, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Yiting Guo
- Department of Radiology, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Hongling Jia
- Department of Acupuncture, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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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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Omoloye A, Weisenburger S, Lehner MD, Gronier B. Menthacarin treatment attenuates nociception in models of visceral hypersensitivity. Neurogastroenterol Motil 2024; 36:e14760. [PMID: 38361164 DOI: 10.1111/nmo.14760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 12/14/2023] [Accepted: 01/30/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Chronic visceral hypersensitivity is closely associated with irritable bowel syndrome (IBS), a very common disorder which significantly impairs quality of life, characterized by abdominal pain, and distension. Imaging studies have found that IBS patients show higher metabolic activities and functional differences from normal controls in the anterior cingulate cortex (ACC), in response to visceral pain stimulation. Non-clinical data and clinical data suggest that medicinal products containing essential oils such as peppermint or caraway oil exert beneficial effects on IBS symptoms. METHODS We assessed acute and long-term treatment effects of a mixture of peppermint and caraway essential oils (Menthacarin) on brain electrophysiological markers of gut pain sensitivity in two rat models of visceral hypersensitivity. KEY RESULTS Chronic administration of corticosteroids and acute repeated mechanical hyperstimulation under anesthesia induced hyperalgesia and hypersensitivity, characterized by an increase in electrophysiological excitatory responses of ACC neurons to colorectal distension (CRD) and an increase in the proportion of neurons responding to otherwise subthreshold stimulation, respectively. Long-term, but not acute, oral administration of Menthacarin (60 mg kg-1 day-1) significantly reduced the net excitatory response to CRD in normally responsive control animals and counteracted the development of visceral hyperalgesia and hypersensitivity induced by repeated corticosterone administration and acute mechanical stimulation. CONCLUSIONS & INFERENCES The present study shows that, using the CRD method, chronic Menthacarin administration at a clinically relevant dose attenuates the neuronal discharge associated with visceral pain stimuli in the rat ACC, particularly in models of hypersensitivity, suggesting a potential for treating exaggerated visceral pain sensitivity.
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Affiliation(s)
- Adesina Omoloye
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester, UK
| | | | - Martin D Lehner
- Preclinical R&D, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany
| | - Benjamin Gronier
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester, UK
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Cui L, Zou S, Liu J, Lv H, Li H, Zhang Z. Potential effects of sodium hyaluronate on constipation-predominant irritable bowel syndrome. Int Immunopharmacol 2024; 127:111404. [PMID: 38128311 DOI: 10.1016/j.intimp.2023.111404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/25/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023]
Abstract
Treatment strategies for constipation-predominant irritable bowel syndrome (IBS-C) continue to improve. However, effective drugs are still lacking. Herein, we explored whether sodium hyaluronate (SH) could be used to treat IBS-C. The effects of SH with different molecular weights were compared in a rat model of IBS-C. Low-molecular-weight SH (LMW-SH, 5 ∼ 10 kDa), medium-molecular-weight SH (MMW-SH, 200 ∼ 400 kDa), and high-molecular-weight SH (HMW-SH, 1300 ∼ 1500 kDa) were screened for efficacy in IBS-C using the following indicators: body weight, number of fecal pellets, fecal moisture, visceral hypersensitivity, and gastrointestinal transit rate. H-HMW-SH was the most effective in improving IBS-C symptoms. The ELISA kits indicated that H-HMW-SH reduced the levels of pro-inflammatory cytokines IL-1β, IL-18, and TNF-α in IBS-C rats. In addition, both western blot and immunofluorescence analyses showed that H-HMW-SH increased the protein expressions of claudin-1, occludin and zonula occludens-1. Furthermore, H-HMW-SH restored the balance of intestinal flora in different intestinal contents (duodenum, jejunum, ileum, and colon) and feces of rats with IBS-C. Overall, our study illustrates the therapeutic potential of H-HMW-SH in the treatment of IBS-C.
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Affiliation(s)
- Li Cui
- Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China
| | - Shuting Zou
- Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China
| | - Jing Liu
- Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China
| | - Huixia Lv
- School of Pharmacy, China Pharmaceutical University, 211198 Nanjing, China.
| | - Hui Li
- Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China.
| | - Zhenhai Zhang
- Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China.
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Schulz A, Welsch SK, Etringer S, Hansen G, Milbert L, Schneider J, Taddei G, Gomez Bravo R, Lygidakis C, van Dyck Z, Lutz A, Wilmes P, Vögele C. Lower gastric sensitivity in quiescent inflammatory bowel disease than in irritable bowel syndrome. Physiol Behav 2023; 270:114293. [PMID: 37468056 DOI: 10.1016/j.physbeh.2023.114293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 04/18/2023] [Accepted: 07/11/2023] [Indexed: 07/21/2023]
Abstract
OBJECTIVE Visceral hypersensitivity is considered a key symptom in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), both of which seriously affect health-related quality of life (HrQoL). Previous findings are mostly based on invasive procedures that may interfere with the assessment of visceral perception. The current study, therefore, investigates whether IBD and IBS are characterized by altered perception of 'natural' gastric distensions ('interoception'). METHODS Twenty IBD patients in remission (13 Crohn's disease, 7 ulcerative colitis), 12 IBS patients, and 20/12 matched healthy control (HC) individuals, respectively, underwent the water load test, in which they could drink ad libitum until the subjective thresholds of satiation (stage 1) and fullness (stage 2) were reached. Gastric motility was assessed using electrogastrography. RESULTS IBD patients drank significantly more water until satiation than IBS patients, whereas no differences between patients and HC groups were observed. Electrogastrographic patterns were comparable between groups, suggesting no pathologies in gastric motility in IBD or IBS. The amount of water consumed until satiation negatively correlated with HrQoL related to bowel symptoms in IBD patients, but was positively associated with emotional well-being in IBS patients. CONCLUSION Our findings implicate relative gastric hypersensitivity in IBS, and relative hyposensitivity in IBD patients, which are both related to specific HrQoL aspects.
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Affiliation(s)
- André Schulz
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Institute for Cognitive and Affective Neuroscience, Trier University, Trier, Germany.
| | - Sina-Katharina Welsch
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Sarah Etringer
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Greta Hansen
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Léa Milbert
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Jochen Schneider
- Saarland University Medical Center, Department of Internal Medicine II, Homburg/Saar, Germany; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Department of Gastroenterology, Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette, Luxembourg
| | - Gennaro Taddei
- Department of Gastroenterology, Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette, Luxembourg
| | - Raquel Gomez Bravo
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Charilaos Lygidakis
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Zoé van Dyck
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Annika Lutz
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Paul Wilmes
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Claus Vögele
- Clinical Psychophysiology Laboratory, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg
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Zandalasini M, Pelizzari L, Ciardi G, Giraudo D, Guasconi M, Paravati S, Lamberti G, Frizziero A. Bowel dysfunctions after acquired brain injury: a scoping review. Front Hum Neurosci 2023; 17:1146054. [PMID: 37900728 PMCID: PMC10602674 DOI: 10.3389/fnhum.2023.1146054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Bowel dysfunction is a common consequence of neurological diseases and has a major impact on the dignity and quality of life of patients. Evidence on neurogenic bowel is focused on spinal cord injury and multiple sclerosis; few studies have focused on patients with acquired brain injury (ABI). Neurogenic bowel dysfunction is related to a lifelong condition derived from central neurological disease, which further increases disability and social deprivation. The manifestations of neurogenic bowel dysfunction include fecal incontinence and constipation. Almost two out of three patients with central nervous system disorder have bowel impairment. This scoping review aims to comprehend the extent and type of evidence on bowel dysfunction after ABI and present conservative treatment. For this scoping review, the PCC (population, concept, and context) framework was used: patients with ABI and bowel dysfunction; evaluation and treatment; and intensive/extensive rehabilitation path. Ten full-text articles were included in the review. Oral laxatives are the most common treatment. The Functional Independence Measure (FIM) subscale is the most common scale used to assess neurogenic bowel disease (60%), followed by the Rome II and III criteria, and the colon transit time is used to test for constipation; however, no instrumental methods have been used for incontinence. An overlapping between incontinence and constipation, SCI and ABI increase difficulties to manage NBD. The need for a consensus between the rehabilitative and gastroenterological societies on the diagnosis and medical care of NBD. Systematic review registration Open Science Framework on August 16, 2022 https://doi.org/10.17605/OSF.IO/NEQMA.
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Affiliation(s)
- Matteo Zandalasini
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
| | - Laura Pelizzari
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
| | - Gianluca Ciardi
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Donatella Giraudo
- Department of Urology, San Raffaele Hospital, Ville Turro, Milan, Italy
| | - Massimo Guasconi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Dipartimento della Direzione delle Professioni Sanitarie, Azienda USL Piacenza, Piacenza, Italy
| | - Stefano Paravati
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
| | - Gianfranco Lamberti
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Antonio Frizziero
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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Hasan SS, Ballou S, Keefer L, Vasant DH. Improving access to gut-directed hypnotherapy for irritable bowel syndrome in the digital therapeutics' era: Are mobile applications a "smart" solution? Neurogastroenterol Motil 2023; 35:e14554. [PMID: 36847206 DOI: 10.1111/nmo.14554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 02/11/2023] [Accepted: 02/14/2023] [Indexed: 03/01/2023]
Abstract
Gut-directed hypnotherapy (GDH) is a highly effective brain-gut behavioral therapy which is recommended in international guidelines for the treatment of irritable bowel syndrome (IBS). There is increasing recognition of the value of GDH as part of integrated care alongside medical and dietary approaches. This has led to recent innovations to widen access to GDH to meet the increasing demand. Recent advances include streamlined courses of individualized GDH, group therapy, and remote delivery. In this issue of Neurogastroenterology and Motility, Peters et al. retrospectively report outcomes of smartphone app-delivered GDH in a population with self-reported IBS. While adherence was low, those that completed smart phone-delivered GDH-achieved symptom benefit. This mini-review summarizes the current evidence-base for available modalities of GDH and discusses the current and future utility and development of mobile health applications in the digital therapeutics' era.
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Affiliation(s)
- Syed S Hasan
- Neurogastroenterology Unit, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
| | - Sarah Ballou
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Laurie Keefer
- The Henry D. Janowitz Division of Gastroenterology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Dipesh H Vasant
- Neurogastroenterology Unit, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
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12
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Clinical Hypnosis for Pediatric Gastrointestinal Disorders: A Practical Guide for Clinicians. J Pediatr Gastroenterol Nutr 2023; 76:271-277. [PMID: 36318870 DOI: 10.1097/mpg.0000000000003651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Functional abdominal pain disorders (FAPDs) are common in the pediatric population and are associated with a significant reduction in quality of life. Bidirectional communication of the brain-gut axis plays an important role in pain generation and perception in FAPDs. There is a paucity of data on the best approach to treat this group of disorders, with no Food and Drug Administration (FDA)-approved drugs and scarce research to substantiate the use of most medications. Use of hypnosis in pediatric FAPDs is supported by evidence and has long-term benefits of up to at least 5 years beyond completion of treatment, highlighting the importance of incorporating this therapy into the care of these patients. The mechanisms by which clinical hypnosis is beneficial in the treatment of FAPDs is not completely understood, but there is growing evidence that it impacts functioning of the brain-gut axis, potentially through influence on central pain processing, visceral sensitivity, and motility. The lack of side effects or potential for significant harm and low cost makes it an attractive option compared to pharmacologic therapies. This review addresses current barriers to clinical hypnosis including misconceptions among patients and families, lack of trained clinicians, and questions around insurance reimbursement. The recent use of telemedicine and delivery of hypnosis via audio-visual modalities allow more patients to benefit from this treatment. As the evidence base for hypnosis grows, acceptance and training will likely increase as well. Further research is needed to understand how hypnosis works and to develop tools that predict who is most likely to respond to hypnosis. Studies on cost-effectiveness in comparing hypnosis to other therapies for FAPDs will increase evidence for appropriate healthcare utilization. Because hypnosis has applications beyond pain and is child-friendly with minimal to no risk, hypnosis could be an important therapeutic tool in the wider pediatric gastrointestinal population.
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13
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Alam MJ, Chen JDZ. Electrophysiology as a Tool to Decipher the Network Mechanism of Visceral Pain in Functional Gastrointestinal Disorders. Diagnostics (Basel) 2023; 13:627. [PMID: 36832115 PMCID: PMC9955347 DOI: 10.3390/diagnostics13040627] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 01/27/2023] [Accepted: 02/07/2023] [Indexed: 02/11/2023] Open
Abstract
Abdominal pain, including visceral pain, is prevalent in functional gastrointestinal (GI) disorders (FGIDs), affecting the overall quality of a patient's life. Neural circuits in the brain encode, store, and transfer pain information across brain regions. Ascending pain signals actively shape brain dynamics; in turn, the descending system responds to the pain through neuronal inhibition. Pain processing mechanisms in patients are currently mainly studied with neuroimaging techniques; however, these techniques have a relatively poor temporal resolution. A high temporal resolution method is warranted to decode the dynamics of the pain processing mechanisms. Here, we reviewed crucial brain regions that exhibited pain-modulatory effects in an ascending and descending manner. Moreover, we discussed a uniquely well-suited method, namely extracellular electrophysiology, that captures natural language from the brain with high spatiotemporal resolution. This approach allows parallel recording of large populations of neurons in interconnected brain areas and permits the monitoring of neuronal firing patterns and comparative characterization of the brain oscillations. In addition, we discussed the contribution of these oscillations to pain states. In summary, using innovative, state-of-the-art methods, the large-scale recordings of multiple neurons will guide us to better understanding of pain mechanisms in FGIDs.
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Affiliation(s)
- Md Jahangir Alam
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Jiande D. Z. Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
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14
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Burgess Robinson L. Exchanges between the gastrointestinal system and the brain. INTRODUCTION TO QUANTITATIVE EEG AND NEUROFEEDBACK 2023:413-425. [DOI: 10.1016/b978-0-323-89827-0.00003-6] [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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15
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Satiamurthy R, Yaakob NS, Shah NM, Azmi N, Omar MS. Potential Roles of 5-HT 3 Receptor Antagonists in Reducing Chemotherapy-induced Peripheral Neuropathy (CIPN). Curr Mol Med 2023; 23:341-349. [PMID: 35549869 DOI: 10.2174/1566524022666220512122525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/10/2022] [Accepted: 01/20/2022] [Indexed: 11/22/2022]
Abstract
5-HT3 receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in chemotherapy patients. However, current and previous studies reveal novel potentials of those ligands in other diseases involving the nervous system, such as addiction, pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and cognitive function. This review gathers existing studies to support the role of 5-HT3 receptors in CIPN modulation. It has been reported that chemotherapy drugs increase the 5-HT content that binds with the 5-HT3 receptor, which later induces pain. As also shown in pre-clinical and clinical studies that various neuropathic pains could be blocked by the 5-HT3 receptor antagonists, we proposed that 5-HT3 receptor antagonists via 5- HT3 receptors may also inhibit neuropathic pain induced by chemotherapy. Our review suggests that future studies focus more on the 5-HT3 receptor antagonists and their modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related pain.
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Affiliation(s)
- Raajeswari Satiamurthy
- Centre for Drug and Herbal Development, Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nor Syafinaz Yaakob
- Centre for Drug and Herbal Development, Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Noraida Mohamed Shah
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Norazrina Azmi
- Centre for Drug and Herbal Development, Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Marhanis Salihah Omar
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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16
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Neshatian L, Karmonik C, Khavari R, Shi Z, Elias S, Boone T, Quigley EMM. Alterations in brain activation patterns in women with functional defecatory disorder: A novel fMRI rectal balloon expulsion study. Neurogastroenterol Motil 2022; 34:e14389. [PMID: 35478218 DOI: 10.1111/nmo.14389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 03/09/2022] [Accepted: 04/11/2022] [Indexed: 12/07/2022]
Abstract
BACKGROUND Functional defecatory disorders (FDD) are common among women. Despite the extensive research on peripheral mechanisms involved in FDD, the central-neural contribution to its pathophysiology remains poorly understood. We aimed to delineate specific supra-spinal regions involved in defecation and examine whether their activity, as measured by blood-oxygen-level-dependent (BOLD) signals, is different in FDD. METHODS We performed functional MRI (fMRI) with concurrent rectal manometry in 15 controls and 18 females with ROME III diagnosis of FDD. A block design was used and brain activation maps based on BOLD effect employing the generalized linear model were calculated for each subject. Statistical significance between groups was assessed by a Student t-test with cluster-based multiple comparisons correction (corrected p < 0.01). KEY RESULTS Simulated defecation was associated with activation of regions of primary and supplementary motor (SMA) and somatosensory cortices, homeostatic afferent (thalamus, mid-cingulate cortex, and insula), and emotional arousal networks (hippocampus and prefrontal cortex), occipital and cerebellum along with deactivation of right anterior cingulate cortex (ACC) in controls. Women with FDD had fewer regions engaged in defecation and BOLD activation was much decreased is areas related to executive-cognitive function (insula, parietal, and prefrontal cortices). Patients unlike controls showed activation in right ACC and otherwise had similar brain activation patterns during anal squeeze. CONCLUSIONS & INFERENCES Our results provide evidence that distinct differences exist in supra-spinal control of defecation in key regions of motivational-affective regulation and executive-cognitive function, in patients with FDD as compared to controls.
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Affiliation(s)
- Leila Neshatian
- Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
| | - Christof Karmonik
- Translational Imaging Center, Houston Methodist Research Institute, Houston, Texas, USA
| | - Rose Khavari
- Department of Urology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
| | - Zhaoyue Shi
- Translational Imaging Center, Houston Methodist Research Institute, Houston, Texas, USA
| | - Saba Elias
- Translational Imaging Center, Houston Methodist Research Institute, Houston, Texas, USA
| | - Timothy Boone
- Department of Urology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
| | - Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
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17
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Fujii R, Awaga Y, Nozawa K, Matsushita M, Hama A, Natsume T, Takamatsu H. Regional brain activation during rectal distention and attenuation with alosetron in a nonhuman primate model of irritable bowel syndrome. FASEB Bioadv 2022; 4:694-708. [PMID: 36349296 PMCID: PMC9635009 DOI: 10.1096/fba.2022-00048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 09/08/2024] Open
Abstract
Greater understanding of the mechanism that mediates visceral pain and hypersensitivity associated with irritable bowel syndrome (IBS) would facilitate the development of effective therapeutics to manage these symptoms. An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brain activation evoked by rectal distention with functional magnetic resonance imaging (fMRI) in a cynomolgus macaque model of visceral hypersensitivity. Male, cynomolgus macaques underwent five four-week treatments of dextran sodium sulfate (DSS)-distilled water (DW), which induced mild-moderate colitis with remission during each treatment cycle. Balloon rectal distention (RD) was performed under anesthesia 14 weeks after the final DSS-DW treatment. Colonoscopy confirmed the absence of colitis prior to the start of RD. In naïve, untreated macaques, 10, 20 and 30 ml RD did not evoke brain activation. However, insular cortex/somatosensory II cortex and cerebellum were significantly activated in DSS-treated macaques at 20 and 30 ml rectal distention. Intra-rectal pressure after DSS treatment was not significantly different from that of naïve, untreated macaques, indicating lack of alteration of rectal functioning following DSS-treatment. Treatment with 5-HT3 receptor antagonist alosetron (p.o.) reduced distension-evoked brain activation and decreased intra-rectal pressure. The current findings demonstrated activation of brain regions to RD following DSS treatments which was not present in naïve macaques, suggesting visceral hypersensitivity. Brain activation in turn was reduced by alosetron, which could underlie the analgesic effect alosetron in IBS patients.
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Affiliation(s)
| | - Yuji Awaga
- Hamamatsu Pharma Research, Inc.HamamatsuJapan
| | | | | | - Aldric Hama
- Hamamatsu Pharma Research, Inc.HamamatsuJapan
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18
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Affiliation(s)
- Heike Künzel
- Psychosomatische Beratungsstelle / Ambulanz, Klinikum Innenstadt d. LMU München, Pettenkoferstraße 8 a, 80336, München, Deutschland.
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19
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Zhan TT, Dong ZY, Yi LS, Zhang Y, Sun HH, Zhang HQ, Wang JW, Chen Y, Huang Y, Xu SC. Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats. Front Cell Neurosci 2022; 16:922750. [PMID: 36072567 PMCID: PMC9441562 DOI: 10.3389/fncel.2022.922750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 07/28/2022] [Indexed: 11/21/2022] Open
Abstract
Tandospirone, a third-generation of antianxiety agent with fewer side effects, has been widely used in the treatment of anxiety. Moreover, it is interesting that tandospirone has been found to relieve gastrointestinal symptoms in patients with refractory irritable bowel syndrome who also have psychological dysfunctions. However, the underlying mechanism remains unclear. In this study, using a visceral hypersensitivity rat model induced by chronic water avoidance stress to mimic the symptoms of irritable bowel syndrome, we found that tandospirone relieved anxiety-like behavior and visceral hypersensitivity induced by stress. Meanwhile, stressed rats had increased 5-HT concentration, less 5-HT1A receptor expression, and enhanced theta oscillations in the anterior cingulate cortex (ACC). Furthermore, the power of the theta band in ACC is positively correlated with the level of visceral sensitivity. Activation of 5-HT1A receptors by its agonist, 8-OH-DPAT, to compensate for their effect in ACC reduced the enhancement of theta oscillations in ACC slices in stressed rats, whereas 5-HT1A receptor antagonist, WAY100135, facilitates theta oscillations in slices of normal rats. Tandospirone reduced the enhancement of theta band power in ACC in vitro and in vivo, thus alleviating anxiety-like behavior and visceral hypersensitivity through 5-HT1A receptors in stressed rats. These results suggest a novel mechanism by which tandospirone activates 5-HT1A receptors to relieve stress-induced anxiety and visceral hypersensitivity by suppressing theta oscillation enhancement in ACC.
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Affiliation(s)
- Ting-Ting Zhan
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zhi-Yu Dong
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Li-Sha Yi
- Department of Gastroenterology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Yan Zhang
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hui-Hui Sun
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hai-Qin Zhang
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jun-Wen Wang
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ying Chen
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ying Huang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Ministry of Education), Department of Physiology and Pharmacology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- *Correspondence: Ying Huang,
| | - Shu-Chang Xu
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Shu-Chang Xu,
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20
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Sasegbon A, Hasan SS, Whorwell PJ, Vasant DH. Experience and clinical efficacy of gut‐directed hypnotherapy in an Asian population with refractory irritable bowel syndrome. JGH OPEN 2022; 6:447-453. [PMID: 35822122 PMCID: PMC9260202 DOI: 10.1002/jgh3.12770] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/29/2022] [Accepted: 05/08/2022] [Indexed: 12/17/2022]
Abstract
Background and Aim Recent studies have highlighted the high worldwide prevalence of irritable bowel syndrome (IBS) and disparities in its management between ethnic groups. For instance, gut‐directed hypnotherapy (GDH), one of the most effective evidence‐based treatments for IBS, is not recommended in Asian countries partly due to lack of population‐specific outcome data. In this context, we evaluated the outcomes of GDH in an Asian population. Methods Consecutive British Asian patients with refractory IBS who received 12‐sessions of GDH using the Manchester protocol were included. Patients were treated by a team including a therapist able to speak several Asian languages. All patients prospectively completed the following questionnaires before and after GDH: IBS symptom severity score (IBS‐SSS), hospital anxiety and depression scale (HADS), non‐colonic symptom score, and the quality‐of‐life (QOL) score. The primary outcome measure was response to GDH defined by ≥50‐point reduction in IBS‐SSS. Pre‐ and post‐treatment data were compared statistically. Results Forty‐four Asian patients with IBS (age 49 ± 13 years; 29 [66%] female; baseline IBS‐SSS: 332.8 ± 94.6) completed GDH. Overall, 37 of 44 (84%) achieved a ≥50‐point reduction in IBS‐SSS and 25 of 44 (57%) achieved ≥30% reduction in abdominal pain scores. Following GDH, there were also significant mean improvements in IBS‐SSS (−132.1, P < 0.0001), non‐colonic symptom score (P < 0.0001), QOL score (P < 0.0001), HADS‐anxiety (P < 0.0001), and HADS‐depression (P < 0.0001), compared with baseline. Conclusion Regardless of the ethnicity of the therapist, GDH was highly effective with similar response rates to outcomes in other IBS populations, supporting the development of GDH in Asian countries.
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Affiliation(s)
- Ayodele Sasegbon
- Neurogastroenterology Unit, Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK
- Division of Diabetes, Endocrinology and Gastroenterology University of Manchester Manchester UK
| | - Syed S Hasan
- Neurogastroenterology Unit, Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK
- Division of Diabetes, Endocrinology and Gastroenterology University of Manchester Manchester UK
| | - Peter J Whorwell
- Neurogastroenterology Unit, Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK
- Division of Diabetes, Endocrinology and Gastroenterology University of Manchester Manchester UK
| | - Dipesh H Vasant
- Neurogastroenterology Unit, Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK
- Division of Diabetes, Endocrinology and Gastroenterology University of Manchester Manchester UK
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21
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Nisticò V, Rossi RE, D'Arrigo AM, Priori A, Gambini O, Demartini B. Functional neuroimaging in Irritable Bowel Syndrome: a systematic review highlights common brain alterations with Functional Movement Disorders. J Neurogastroenterol Motil 2022; 28:185-203. [PMID: 35189600 PMCID: PMC8978134 DOI: 10.5056/jnm21079] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 09/03/2021] [Accepted: 11/24/2021] [Indexed: 12/02/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurring abdominal pain and altered bowel habits without detectable organic causes. This study aims to provide a comprehensive overview of the literature on functional neuroimaging in IBS and to highlight brain alterations similarities with other functional disorders - functional movement disorders in particular. We conducted the bibliographic search via PubMed in August 2020 and included 50 studies following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. Overall, our findings showed an aberrant activation and functional connectivity of the insular, cingulate, sensorimotor and frontal cortices, the amygdala and the hippocampus, suggesting an altered activity of the homeostatic and salience network and of the autonomous nervous system. Moreover, glutamatergic dysfunction in the anterior insula and hypothalamic pituitary axis dysregulation were often reported. These alterations seem to be very similar to those observed in patients with functional movement disorders. Hence, we speculate that different functional disturbances might share a common pathophysiology and we discussed our findings in the light of a Bayesian model framework.
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Affiliation(s)
- Veronica Nisticò
- Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.,"Aldo Ravelli" Research Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy.,Department of Psychology, University of Milan-Bicocca, Milan, Italy
| | - Roberta E Rossi
- Gastro-intestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,Department of Pathophysiology and Organ Transplant, Università degli Studi di Milano, Milan, Italy
| | - Andrea M D'Arrigo
- Department of Neurology, ASST Fatebenefratelli Sacco, Ospedale Fatebenefratelli, Milan, Italy
| | - Alberto Priori
- Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.,"Aldo Ravelli" Research Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy.,III Clinica Neurologica, ASST Santi Paolo e Carlo, Presidio San Paolo, Milan, Italy
| | - Orsola Gambini
- Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.,"Aldo Ravelli" Research Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy.,Unità di Psichiatria 52, ASST Santi Paolo e Carlo, Presidio San Paolo, Milan, Italy
| | - Benedetta Demartini
- Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.,"Aldo Ravelli" Research Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy.,Unità di Psichiatria 52, ASST Santi Paolo e Carlo, Presidio San Paolo, Milan, Italy
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22
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Matisz C, Gruber A. Neuroinflammatory remodeling of the anterior cingulate cortex as a key driver of mood disorders in gastrointestinal disease and disorders. Neurosci Biobehav Rev 2022; 133:104497. [DOI: 10.1016/j.neubiorev.2021.12.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 11/10/2021] [Accepted: 12/09/2021] [Indexed: 02/08/2023]
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23
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Islam Z, D'Silva A, Raman M, Nasser Y. The role of mind body interventions in the treatment of irritable bowel syndrome and fibromyalgia. Front Psychiatry 2022; 13:1076763. [PMID: 36620663 PMCID: PMC9814478 DOI: 10.3389/fpsyt.2022.1076763] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Irritable bowel syndrome and fibromyalgia share similar pathophysiologic mechanisms including sensitization of peripheral and central pain pathways, autonomic dysfunction and are often co-diagnosed. Co-diagnosed patients experience increased symptom severity, mental health comorbidities, and decreased quality of life. The role of mind-body interventions, which have significant effects on central pain syndromes and autonomic dysregulation, have not been well-described in co-diagnosed patients. The aim of this state-of-the art narrative review is to explore the relationship between irritable bowel syndrome and fibromyalgia, and to evaluate the current evidence and mechanism of action of mind-body therapies in these two conditions. METHODS The PubMed database was searched without date restrictions for articles published in English using the following keywords: fibromyalgia, irritable bowel syndrome, mind-body interventions, cognitive behavioral therapy, mindfulness based stress reduction, and yoga. RESULTS Mind-body interventions resulted in improved patient-reported outcomes, and are effective for irritable bowel syndrome and fibromyalgia individually. Specifically, cognitive behavioral therapy and yoga trials showed decreased symptom severity, improved mental health, sleep and quality of life for both conditions individually, while yoga trials demonstrated similar benefits with improvements in both physical outcomes (gastrointestinal symptoms, pain/tenderness scores, insomnia, and physical functioning), mental health outcomes (anxiety, depression, gastrointestinal-specific anxiety, and catastrophizing), and quality of life, possibly due to alterations in autonomic activity. CONCLUSION Mind-body interventions especially CBT and yoga improve patient-reported outcomes in both irritable bowel syndrome and fibromyalgia individually. However, limited available data in co-diagnosed patients warrant high quality trials to better tailor programs to patient needs.
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Affiliation(s)
- Zarmina Islam
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Adrijana D'Silva
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Maitreyi Raman
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.,Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Yasmin Nasser
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.,Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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24
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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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Kosek E, Clauw D, Nijs J, Baron R, Gilron I, Harris RE, Mico JA, Rice ASC, Sterling M. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain 2021; 162:2629-2634. [PMID: 33974577 DOI: 10.1097/j.pain.0000000000002324] [Citation(s) in RCA: 245] [Impact Index Per Article: 61.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 03/18/2021] [Indexed: 11/26/2022]
Affiliation(s)
- Eva Kosek
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Daniel Clauw
- Department of Anesthesiology, Chronic Pain and Fatigue Research Center, The University of Michigan, Ann Arbor, MI, United States
| | - Jo Nijs
- Pain in Motion International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Ixelles, Belgium
- Chronic Pain Rehabilitation, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium
- Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Ralf Baron
- Division of Neurological Pain Research and -therapy, Department of Neurology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany
| | - Ian Gilron
- Departments of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Centre for Neuroscience Studies, and School of Policy Studies, Queen's University, Kingston, ON, Canada
| | - Richard E Harris
- Department of Anesthesiology, Chronic Pain and Fatigue Research Center, The University of Michigan, Ann Arbor, MI, United States
| | - Juan-Antonio Mico
- Department of Neuroscience, Pharmacology & Psychiatry, Biomedical Research Center on Mental Health (CIBERSAM), University of Cádiz, Cádiz, Spain
| | - Andrew S C Rice
- Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom
| | - Michele Sterling
- RECOVER Injury Research Centre, The University of Queensland, Herston, Australia
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26
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Mohebbi Z, Firoozabadi A, Naini MA, Sharif F, Keshtkaran Z, Heydari N. Effect of Hypnotism on the Severity of Gastrointestinal Symptoms and Quality of Life in Individuals With Irritable Bowel Syndrome. J Psychosoc Nurs Ment Health Serv 2021; 60:55-62. [PMID: 34677120 DOI: 10.3928/02793695-20211014-04] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The current study aimed to determine the effects of hypnotism on the severity of gastrointestinal symptoms and quality of life in individuals with irritable bowel syndrome (IBS). This trial study was conducted on 100 people with IBS in Shiraz, Iran. Hypnotism of participants was performed in 1-hour sessions for the intervention group at Weeks 4 and 6. A demographic characteristic questionnaire, Gastrointestinal Symptom Rating Scale, and IBS Quality of Life Index were used for data collection. The severity of gastrointestinal symptoms of participants in the intervention group significantly improved at 6 and 15 weeks after hypnotherapy. These individuals also had a significantly better quality of life after 15 weeks of hypnotherapy. Hypnotherapy may be beneficial in reducing gastrointestinal symptoms and improving quality of life in individuals with IBS. Combining this method with medicinal treatments could be effective for patients and health systems. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].
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27
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Kanjanawasee D, Campbell RG, Rimmer J, Alvarado R, Kanjanaumporn J, Snidvongs K, Kalish L, Harvey RJ, Sacks R. Empty Nose Syndrome Pathophysiology: A Systematic Review. Otolaryngol Head Neck Surg 2021; 167:434-451. [PMID: 34665687 DOI: 10.1177/01945998211052919] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The pathophysiology of empty nose syndrome (ENS) remains unclear despite significant research. The pathophysiologic mechanism of ENS was systematically reviewed. DATA SOURCES MEDLINE and Embase. REVIEW METHODS Data were systematically reviewed for studies that provided original data on pathophysiology. RESULTS A total of 2476 studies were screened, and 19 met the inclusion criteria: 13 case-control and 6 cross-sectional. Nine pathophysiologic themes were identified.• Demographics: ENS symptoms had no relationship with climatic factors.• Symptomatology: ENS patients demonstrated high symptom severity.• Mental health: Anxiety and depression including hyperventilation were reported in >50% of ENS patients and correlated with ENS symptom severity.• Anatomic features: Structural changes in response to turbinate surgery were similar between ENS and non-ENS patients.• Airflow analysis: Airflow parameters were similar between ENS and non-ENS patients after turbinate surgery. On computational fluid dynamic analysis, differences were found on multiple outcomes.• Diagnostic testing: The menthol detection test was impaired in ENS, and cotton placement in the airway improved ENS symptoms.• Cognitive function: Functional magnetic resonance imaging showed activation in emotional processing area during breathing.• Olfactory function: Subjective impairment was reported in ENS, but quantitative measures were similar to non-ENS patients.• Mucosal physiology/innate immunity: Turbinate histopathology in ENS showed a tissue-remodeling pattern. Nasal nitric oxide level was lower in ENS patients. CONCLUSION There is evidence of high comorbid mental health disorders in ENS patients. An abnormal trigeminal-thermoreceptor response may be present in some patients. The influence of altered airflow and the evidence of surgery as the cause for ENS are unclear.
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Affiliation(s)
- Dichapong Kanjanawasee
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.,Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Raewyn G Campbell
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.,Department of Otorhinolaryngology-Head and Neck Surgery, Royal Prince Alfred Hospital, Sydney, Australia.,Rhinology and Skull Base Research Group, Applied Medical Research Centre, University of New South Wales, Sydney, Australia
| | - Janet Rimmer
- Rhinology and Skull Base Research Group, Applied Medical Research Centre, University of New South Wales, Sydney, Australia.,Woolcock Institute, University of Sydney, Sydney, Australia.,Faculty of Medicine, Notre Dame University, Sydney, Australia
| | - Raquel Alvarado
- Rhinology and Skull Base Research Group, Applied Medical Research Centre, University of New South Wales, Sydney, Australia
| | - Jesada Kanjanaumporn
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kornkiat Snidvongs
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Larry Kalish
- Rhinology and Skull Base Research Group, Applied Medical Research Centre, University of New South Wales, Sydney, Australia.,Department of Otolaryngology-Head and Neck Surgery, Concord General Hospital, University of Sydney, Australia.,Faculty of Medicine, University of Sydney, Sydney, Australia
| | - Richard J Harvey
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.,Rhinology and Skull Base Research Group, Applied Medical Research Centre, University of New South Wales, Sydney, Australia
| | - Raymond Sacks
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.,Department of Otolaryngology-Head and Neck Surgery, Concord General Hospital, University of Sydney, Australia
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28
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Ma KSK, Lai JN, Veeravalli JJ, Chiu LT, Van Dyke TE, Wei JCC. Fibromyalgia and periodontitis: Bidirectional associations in population-based 15-year retrospective cohorts. J Periodontol 2021; 93:877-887. [PMID: 34542911 DOI: 10.1002/jper.21-0256] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 09/05/2021] [Accepted: 09/06/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND To determine the bidirectional link between periodontitis and fibromyalgia. METHODS In this cohort study, 196,428 periodontitis patients and 196,428 propensity score-matched non-periodontitis controls were enrolled. A Cox proportional hazard model was utilized to estimate the risk of fibromyalgia and survival analysis was adopted to assess the time-dependent effect of periodontitis on fibromyalgia. Subgroup analyses stratified by age, sex, and tracking period were conducted to identify susceptible populations. A parallel and symmetrical cohort that recruited 141,439 fibromyalgia patients and 141,439 propensity score-matched non-fibromyalgia controls ascertained the inverse effect of fibromyalgia on incident periodontitis. RESULTS Patients with periodontitis were more likely to develop fibromyalgia than non-periodontitis controls (HR = 1.42, 95% CI = 1.39-1.44, P < 0.001), which persisted in the survival analysis (log-rank test P < 0.0001). This effect was significant in both sexes and all age subgroups, and was particularly evident in males (HR = 1.52, 95% CI = 1.48-1.56, P < 0.001) and younger periodontitis patients (HR = 1.55, 95% CI = 1.50-1.60, P < 0.001). Fibromyalgia patients who never had periodontitis presented with greater risk for periodontitis over time (HR = 1.43, 95% CI = 1.40 - 1.45, P < 0.001; log-rank test P < 0.0001). CONCLUSIONS Patients of both sexes and all age subgroups with periodontitis presented with a greater risk of fibromyalgia. Subgroups that were the most susceptible to periodontitis-associated fibromyalgia were periodontitis patients that were males and below 30 years old. Risks of periodontitis were also greater in fibromyalgia patients who never had periodontitis.
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Affiliation(s)
- Kevin Sheng-Kai Ma
- Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Graduate Institute of Biomedical Electronics and Bioinformatics, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan.,Department of Dentistry, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Jung-Nien Lai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.,Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
| | - John Jims Veeravalli
- Department of Dentistry, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Lu-Ting Chiu
- Clinical Trial Research Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Thomas E Van Dyke
- Center for Clinical and Translational Research, Forsyth Institute, Cambridge, Massachusetts, USA.,Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - James Cheng-Chung Wei
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.,Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
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29
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Jagielski CH, Riehl ME. Behavioral Strategies for Irritable Bowel Syndrome: Brain-Gut or Gut-Brain? Gastroenterol Clin North Am 2021; 50:581-593. [PMID: 34304789 DOI: 10.1016/j.gtc.2021.03.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI) that is associated with significant physical, emotional, and occupational burden. Factors such as early life stress, sleep disruption, maladaptive coping strategies, symptom hypervigilance, and visceral hypersensitivity negatively affect gut-brain communication and increase the likelihood of developing IBS or worsen IBS severity. Behavioral strategies, such as cognitive behavioral therapy, gut-directed hypnosis, and mindfulness-based treatments, have shown benefit in improving gastrointestinal (GI)-specific quality of life, as well as reducing GI symptoms. Partnering with a GI-specific mental health provider can assist gastroenterologists in providing comprehensive treatment of IBS and other DGBIs.
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Affiliation(s)
- Christina H Jagielski
- Internal Medicine-Gastroenterology, Michigan Medicine, 380 Parkland Plaza, Ann Arbor, MI 48103, USA.
| | - Megan E Riehl
- Internal Medicine-Gastroenterology, Michigan Medicine, 3912 Taubman Center, SPC 5362, Suite 3436, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5362, USA
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30
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Yang LK, Lu L, Feng B, Wang XS, Yue J, Li XB, Zhuo M, Liu SB. FMRP acts as a key messenger for visceral pain modulation. Mol Pain 2021; 16:1744806920972241. [PMID: 33243040 PMCID: PMC7786421 DOI: 10.1177/1744806920972241] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Visceral pain is a common clinical symptom, which is caused by mechanical stretch, spasm, ischemia and inflammation. Fragile X syndrome (FXS) with lack of fragile X mental retardation protein (FMRP) protein is an inherited disorder that is characterized by moderate or severe intellectual and developmental disabilities. Previous studies reported that FXS patients have self-injurious behavior, which may be associated with deficits in nociceptive sensitization. However, the role of FMRP in visceral pain is still unclear. In this study, the FMR1 knock out (KO) mice and SH-SY5Y cell line were employed to demonstrate the role of FMRP in the regulation of visceral pain. The data showed that FMR1 KO mice were insensitive to zymosan treatment. Recording in the anterior cingulate cortex (ACC), a structure involved in pain process, showed less presynaptic glutamate release and postsynaptic responses in the FMR1 KO mice as compared to the wild type (WT) mice after zymosan injection. Zymosan treatment caused enhancements of adenylyl cyclase 1 (AC1), a pain-related enzyme, and NMDA GluN2B receptor in the ACC. However, these up-regulations were attenuated in the ACC of FMR1 KO mice. Last, we found that zymosan treatment led to increase of FMRP levels in the ACC. These results were further confirmed in SH-SY5Y cells in vitro. Our findings demonstrate that FMRP is required for NMDA GluN2B and AC1 upregulation, and GluN2B/AC1/FMRP forms a positive feedback loop to modulate visceral pain.
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Affiliation(s)
- Liu-Kun Yang
- Department of Pharmacology, School of Pharmacy, 12644Fourth Military Medical University, Xi'an, China
| | - Liang Lu
- Department of Pharmacology, School of Pharmacy, 12644Fourth Military Medical University, Xi'an, China
| | - Ban Feng
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Pharmacy, School of Stomatology, 12644Fourth Military Medical University, Xi'an, China
| | - Xin-Shang Wang
- Department of Pharmacology, School of Pharmacy, 12644Fourth Military Medical University, Xi'an, China
| | - Jiao Yue
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Pharmacy, School of Stomatology, 12644Fourth Military Medical University, Xi'an, China
| | - Xu-Bo Li
- Department of Pharmacology, School of Pharmacy, 12644Fourth Military Medical University, Xi'an, China
| | - Min Zhuo
- Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiao Tong University, Xi'an, China
| | - Shui-Bing Liu
- Department of Pharmacology, School of Pharmacy, 12644Fourth Military Medical University, Xi'an, China
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31
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Abnormalities in the thalamo-cortical network in patients with functional constipation. Brain Imaging Behav 2021; 15:630-642. [PMID: 32314199 DOI: 10.1007/s11682-020-00273-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.
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32
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Xiao X, Ding M, Zhang YQ. Role of the Anterior Cingulate Cortex in Translational Pain Research. Neurosci Bull 2021; 37:405-422. [PMID: 33566301 PMCID: PMC7954910 DOI: 10.1007/s12264-020-00615-2] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023] Open
Abstract
As the most common symptomatic reason to seek medical consultation, pain is a complex experience that has been classified into different categories and stages. In pain processing, noxious stimuli may activate the anterior cingulate cortex (ACC). But the function of ACC in the different pain conditions is not well discussed. In this review, we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain, neuropathic pain, and cancer pain in the ACC, and discuss the cellular receptors and signaling molecules from animal studies. We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management. The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.
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Affiliation(s)
- Xiao Xiao
- Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education; Institute of Science and Technology for Brain-Inspired Intelligence, Behavioral and Cognitive Neuroscience Center, Fudan University, Shanghai, 200433, China.
| | - Ming Ding
- Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education; Institute of Science and Technology for Brain-Inspired Intelligence, Behavioral and Cognitive Neuroscience Center, Fudan University, Shanghai, 200433, China
| | - Yu-Qiu Zhang
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, Institutes of Brain Science; Institute of Integrative Medicine, Fudan University, Shanghai, 200032, China.
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33
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Yaklai K, Pattanakuhar S, Chattipakorn N, Chattipakorn SC. The Role of Acupuncture on the Gut-Brain-Microbiota Axis in Irritable Bowel Syndrome. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2021; 49:285-314. [PMID: 33622207 DOI: 10.1142/s0192415x21500154] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic dysfunction of the gastrointestinal tract, commonly characterized by abdominal pain or abdominal discomfort. These symptoms can substantially reduce the quality of life and work productivity of the patients. The exact pathogenesis of IBS remains unclear, as it has become apparent that multiple pathways are activated in the condition, including inflammation, immunology, neurology and psychology. Recent evidence has shown that symptoms in IBS are related to the dysfunction of the nervous system, particularly the viscerosomatic pathway, through immune-to-brain communication. The potential link between brain-gut relationships is gut microbiota. The management of IBS mostly focuses on symptomatically treating the patients. There are a wide range of standard treatments, including pharmacological to psychological interventions which are effective in some patients. Therefore, a combination of therapies including both standard and complimentary treatments, including Traditional Chinese Medicine (TCM) such as acupuncture, have been used in treating IBS patients. Several in vivo and clinical studies have demonstrated the efficacy of acupuncture in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture for IBS. This paper summarizes and discusses the possible mechanisms associated with acupuncture on the pathophysiology of IBS, including gastrointestinal (GI) motility, visceral hypersensitivity, the immune system, neurotransmitters, and the brain-gut axis. The results fromin vivo and clinical studies have been included. In addition, the effects of acupuncture on gut microbiota in IBS are included and any contradictory findings are deliberated.
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Affiliation(s)
- Kiangyada Yaklai
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand.,Sriphat Medical Center, Chiang Mai University, Chiang Mai, Thailand
| | - Sintip Pattanakuhar
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand.,Department of Rehabilitation Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand.,Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
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34
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Warren HJM, Ioachim G, Powers JM, Stroman PW. How fMRI Analysis Using Structural Equation Modeling Techniques Can Improve Our Understanding of Pain Processing in Fibromyalgia. J Pain Res 2021; 14:381-398. [PMID: 33603453 PMCID: PMC7882802 DOI: 10.2147/jpr.s290795] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/16/2021] [Indexed: 12/18/2022] Open
Abstract
PURPOSE The purpose of this study was to investigate the utility of data-driven analyses of functional magnetic resonance imaging (fMRI) data, by means of structural equation modeling, for the investigation of pain processing in fibromyalgia (FM). PATIENTS AND METHODS Datasets from two separate pain fMRI studies involving healthy controls (HC) and participants with FM were re-analyzed using both a conventional model-driven approach and a data-driven approach, and the results from these analyses were compared. The first dataset contained 15 women with FM and 15 women as healthy controls. The second dataset contained 15 women with FM and 11 women as healthy controls. RESULTS Consistent with previous studies, the model-driven analyses did not identify differences in pain processing between the HC and FM study groups in both datasets. On the other hand, the data-driven analyses identified significant group differences in both datasets. CONCLUSION Data-driven analyses can enhance our understanding of pain processing in healthy controls and in clinical populations by identifying activity associated with pain processing specific to the clinical groups that conventional model-driven analyses may miss.
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Affiliation(s)
- Howard J M Warren
- Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
| | - Gabriela Ioachim
- Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
| | - Jocelyn M Powers
- Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
| | - Patrick W Stroman
- Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
- Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada
- Department of Physics, Queen’s University, Kingston, Ontario, Canada
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35
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Li C, Shuai Y, Zhou X, Chen H. Association between Helicobacter pylori infection and irritable bowel syndrome: A systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e22975. [PMID: 33327230 PMCID: PMC7738067 DOI: 10.1097/md.0000000000022975] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND In recent years, the incidence of IBS has gradually increased, and it is considered as one of the most common functional gastrointestinal diseases. However, the etiology of IBS is still unclear, and expectations are rising for more targeted treatments. Many clinical trials have explored the link between Helicobacter pylori (H pylori) and IBS, with different conclusions. Therefore, we conducted a meta-analysis to explore whether there is an association between H pylori and IBS, which is of great significance for targeted treatment of IBS. METHODS We performed a systematic review and meta-analysis of the association between H pylori and IBS. We searched PubMed, EMBASE, Medline and the Cochrane Library to collect related studies. OR was used to describe the ratio of the probability of the H pylori infection occurring in IBS patients versus the controls. Heterogeneity was assessed by subgroup and meta-regression analysis. RESULTS Eight studies, including 1861 patients, assessed the association between H pylori infection and IBS. The OR of H pylori in IBS patients compared to controls was 1.32 (95% CI: 0.94-1.87; P = 0.11). Subgroup analyses showed a difference between IBS patients diagnosed with Roman III criteria and those diagnosed with non-Roman III criteria. CONCLUSIONS Our study suggests that H pylori may have a positive effect on the development of IBS. Although the differences were not statistically significant, there were significant differences among subgroups of patients. Considering the limitations and heterogeneity, high quality studies are needed to further explore the effect of H pylori on the development of IBS.
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Affiliation(s)
- Chenyu Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Road, Donghu District, Nanchang, Jiangxi Province
- First Clinical Medical College, Nanchang University, Nanchang, China
| | - Yujun Shuai
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Road, Donghu District, Nanchang, Jiangxi Province
- First Clinical Medical College, Nanchang University, Nanchang, China
| | - Xiaodong Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Road, Donghu District, Nanchang, Jiangxi Province
| | - Hongxia Chen
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Nanchang University
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Chiba T, Ito K, Mori F, Sasaki M, Matsumoto T. Detection of microstructural white matter alterations in functional gastrointestinal disorders assessed by diffusion kurtosis imaging. JGH Open 2020; 4:958-963. [PMID: 33102770 PMCID: PMC7578273 DOI: 10.1002/jgh3.12375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 05/15/2020] [Accepted: 05/29/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM We evaluated whether diffusion kurtosis and tensor imaging (DKI/DTI) could reveal microstructural alterations in the brains of patients with functional gastrointestinal disorders (FGIDs), and whether imaging findings were correlated with health-related quality of life (HRQOL). METHODS Twelve patients with FGIDs fulfilling the Rome IV criteria, and seven healthy controls were examined using a 3 T magnetic resonance (MR) scanner. Tract-based spatial statistics and regions of interest analyses were performed to compare the mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) between patients with FGIDs versus controls. HRQOL was assessed in patients with FGIDs using the eight-item short form of the Medical Outcome Study Questionnaire (SF-8) and the Gastrointestinal Symptom Rating Scale. RESULTS Patients with FGIDs had extensive, widespread regions of reduced MD in the white matter in comparison with healthy controls, whereas no significant differences were observed in MK and FA. No significant differences in deep gray matter for the MK, FA, and MD values were observed between patients with FGIDs and controls. In patients with FGIDs, the FA values in the globus pallidus had a significant and negative correlation with SF-8 (a mental component summary) (r = -0.797, P = 0.01 uncorrected for multiple comparisons). CONCLUSIONS DKI/DTI can help identify microstructural white matter alterations in patients with FGIDs. The FA values in the globus pallidus may be useful for a severity assessment of FGIDs.
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Affiliation(s)
- Toshimi Chiba
- Division of Internal Medicine, Department of Oral MedicineIwate Medical UniversityMoriokaJapan
| | - Kenji Ito
- Division of Ultrahigh Field MRI, Institute for Biomedical SciencesIwate Medical UniversityYahabaJapan
| | - Futoshi Mori
- Division of Ultrahigh Field MRI, Institute for Biomedical SciencesIwate Medical UniversityYahabaJapan
| | - Makoto Sasaki
- Division of Ultrahigh Field MRI, Institute for Biomedical SciencesIwate Medical UniversityYahabaJapan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal MedicineIwate Medical UniversityMoriokaJapan
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Mind and gut: Associations between mood and gastrointestinal distress in children exposed to adversity. Dev Psychopathol 2020; 32:309-328. [PMID: 30919798 DOI: 10.1017/s0954579419000087] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastrointestinal and mental disorders are highly comorbid, and animal models have shown that both can be caused by early adversity (e.g., parental deprivation). Interactions between the brain and bacteria that live within the gastrointestinal system (the microbiome) underlie adversity-gastrointestinal-anxiety interactions, but these links have not been investigated during human development. In this study, we utilized data from a population of 344 youth (3-18 years old) who were raised with their biological parents or were exposed to early adverse caregiving experiences (i.e., institutional or foster care followed by international adoption) to explore adversity-gastrointestinal-anxiety associations. In Study 1, we demonstrated that previous adverse care experiences were associated with increased incidence of gastrointestinal symptoms in youth. Gastrointestinal symptoms were also associated with concurrent and future anxiety (measured across 5 years), and those gastrointestinal symptoms mediated the adversity-anxiety association at Time 1. In a subsample of children who provided both stool samples and functional magnetic resonance imaging of the brain (Study 2, which was a "proof-of-principle"), adversity was associated with changes in diversity (both alpha and beta) of microbial communities, and bacteria levels (adversity-associated and adversity-independent) were correlated with prefrontal cortex activation to emotional faces. Implications of these data for supporting youth mental health are discussed.
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Electroacupuncture Improves IBS Visceral Hypersensitivity by Inhibiting the Activation of Astrocytes in the Medial Thalamus and Anterior Cingulate Cortex. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:2562979. [PMID: 32617101 PMCID: PMC7306073 DOI: 10.1155/2020/2562979] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 05/02/2020] [Accepted: 05/19/2020] [Indexed: 12/12/2022]
Abstract
Objective To explore whether the effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS) is related to the changes of astrocyte activation in the medial thalamus (MT) and anterior cingulate cortex (ACC). Method Male Sprague-Dawley rats were randomly divided into the normal control (NC) group, model control (MC) group, electroacupuncture (EA) group, and fluorocitrate (FCA) group. A model of visceral hypersensitivity was established by neonatal colorectal irritation. In the EA group, needles were inserted into the skin at the Tianshu (ST25) and Shangjuxu (ST37) acupoints, once a day for 7 days. The FCA group received intrathecal injection of FCA on the 1st, 4th, and 7th days. Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex (AWR), and glial fibrillary acidic protein (GFAP) mRNA and protein levels in the MT and ACC were detected by real-time PCR, immunohistochemistry, and western blots. Results The AWR score in the MC group was significantly higher than in the NC group, and EA and FCA reduced the AWR score of VH rats. GFAP mRNA and protein levels in the MT and ACC of rats in the MC group were significantly increased compared with the NC group. After either electroacupuncture or fluorocitrate, GFAP mRNA and protein levels in the MT and ACC were both clearly reduced. Conclusion Electroacupuncture alleviates IBS visceral hypersensitivity by inhibiting the activation of astrocytes in the MT and ACC.
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Wen Y, Li J, Long Q, Yue CC, He B, Tang XG. The efficacy and safety of probiotics for patients with constipation-predominant irritable bowel syndrome: A systematic review and meta-analysis based on seventeen randomized controlled trials. Int J Surg 2020; 79:111-119. [DOI: 10.1016/j.ijsu.2020.04.063] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 04/22/2020] [Accepted: 04/27/2020] [Indexed: 12/18/2022]
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Huang T, Okauchi T, Hu D, Shigeta M, Wu Y, Wada Y, Hayashinaka E, Wang S, Kogure Y, Noguchi K, Watanabe Y, Dai Y, Cui Y. Pain matrix shift in the rat brain following persistent colonic inflammation revealed by voxel-based statistical analysis. Mol Pain 2020; 15:1744806919891327. [PMID: 31709891 PMCID: PMC6886279 DOI: 10.1177/1744806919891327] [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] [Indexed: 12/29/2022] Open
Abstract
Inflammatory bowel disease (IBD), mainly comprising Crohn’s disease and ulcerative colitis, is characterized by chronic inflammation in the digestive tract. Approximately 60% of the patients experience abdominal pain during acute IBD episodes, which severely impairs their quality of life. Both peripheral and central mechanisms are thought to be involved in such abdominal pain in IBD. Although much attention has been paid to peripheral mechanisms of abdominal pain in IBD pathophysiology, the involvement of supraspinal mechanisms remains poorly understood. To address this issue, we investigated regional brain activity in response to colorectal distension in normal and IBD model rats using voxel-based statistical analysis of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography imaging. The rat IBD model was generated by colorectal administration of 2,4,6-trinitrobenzene sulfonic acid, a chemical compound widely used to generate colitis. Tissue damage and inflammation were induced and dynamically changed with time after 2,4,6-trinitrobenzene sulfonic acid injection, while colorectal distension-induced visceromotor response showed corresponding temporal changes. We found that characteristic brain activations were observed in response to visceral innocuous and noxious colorectal distension and supraspinal nociception shared some physiological sensory pathway. Moreover, widespread brain regions were activated, and the functional coupling between the central medial thalamic nucleus and anterior cingulate cortex was enhanced after noxious colorectal distension in IBD model of rats. Increased brain activity in the anterior insular cortex and anterior cingulate cortex was positively correlated with noxious colorectal distension-induced pain severity in normal and IBD rats, respectively. These findings suggest that the pain matrix was shifted following persistent colonic inflammation, and thalamocortical sensitization in the pathway from the central medial thalamic nucleus to anterior cingulate cortex might be a central mechanism of the visceral hyperalgesia in IBD pathophysiology.
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Affiliation(s)
- Tianliang Huang
- Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.,Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Japan.,Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
| | - Takashi Okauchi
- Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Di Hu
- Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Mika Shigeta
- Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Yuping Wu
- Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Yasuhiro Wada
- Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Emi Hayashinaka
- Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Shenglan Wang
- Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
| | - Yoko Kogure
- Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
| | - Koichi Noguchi
- Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yasuyoshi Watanabe
- Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Yi Dai
- Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Japan.,Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
| | - Yilong Cui
- Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
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Balmus IM, Ciobica A, Cojocariu R, Luca AC, Gorgan L. Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status. ACTA ACUST UNITED AC 2020; 56:medicina56040175. [PMID: 32295083 PMCID: PMC7230401 DOI: 10.3390/medicina56040175] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]
Abstract
Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as “irritable bowel syndrome”, “gut brain axis”, “oxidative stress”, “neuroendocrine”, and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development.
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Affiliation(s)
- Ioana-Miruna Balmus
- Department of Interdisciplinary Research in Science, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, No. 11, 700506 Iași, Romania;
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
| | - Alin Ciobica
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Roxana Cojocariu
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
| | - Alina-Costina Luca
- Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 16th University Street, 700115 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Lucian Gorgan
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
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Suciu A, Popa SL, Dumitrascu DL. Upper Gastrointestinal Sensitization And Symptom Generation. J Med Life 2020; 12:316-321. [PMID: 32025247 PMCID: PMC6993284 DOI: 10.25122/jml-2019-0111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders, and their diagnostic criteria are symptom-based, with the absence of anatomical and biochemical abnormalities of the gastrointestinal tract. Chronic visceral symptoms are common both in patients with an identifiable organic disease but also in FGID patients. Patients suffering from upper gastrointestinal functional disorders typically present with various symptoms such as early satiety, postprandial fullness, bloating, nausea, vomiting, and epigastric pain. Considering their increasing prevalence, difficulties in diagnosis, and low quality of life, FGIDs have become an emerging problem in gastroenterology. We aimed to provide an updated summary of pathways involved in visceral sensitization. We examined the recent literature searching for evidence of the most important studies about the mechanisms underlying gastrointestinal symptom generation and sensitization.
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Affiliation(s)
- Alina Suciu
- Second Medical Department "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Romania
| | - Stefan-Lucian Popa
- Second Medical Department "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Romania
| | - Dan-Lucian Dumitrascu
- Second Medical Department "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Romania
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Weaver MJ, McHenry SA, Sayuk GS, Gyawali CP, Davidson NO. Bile Acid Diarrhea and NAFLD: Shared Pathways for Distinct Phenotypes. Hepatol Commun 2020; 4:493-503. [PMID: 32258945 PMCID: PMC7109338 DOI: 10.1002/hep4.1485] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 01/13/2020] [Indexed: 12/16/2022] Open
Abstract
Irritable bowel syndrome with diarrhea (IBS-D) and NAFLD are both common conditions that may be influenced by shared pathways of altered bile acid (BA) signaling and homeostatic regulation. Pathophysiological links between IBS-D and altered BA metabolism include altered signaling through the ileal enterokine and fibroblast growth factor 19 (FGF19) as well as increased circulating levels of 7α-hydroxy-4-cholesten-3-one, a metabolic intermediate that denotes increased hepatic BA production from cholesterol. Defective production or release of FGF19 is associated with increased BA production and BA diarrhea in some IBS-D patients. FGF19 functions as a negative regulator of hepatic cholesterol 7α-hydroxylase; therefore, reduced serum FGF19 effectively de-represses hepatic BA production in a subset of IBS-D patients, causing BA diarrhea. In addition, FGF19 modulates hepatic metabolic homeostatic response signaling by means of the fibroblast growth factor receptor 4/klotho beta receptor to activate cascades involved in hepatic lipogenesis, fatty acid oxidation, and insulin sensitivity. Emerging evidence of low circulating FGF19 levels in subsets of patients with pediatric and adult NAFLD demonstrates altered enterohepatic BA homeostasis in NAFLD. Conclusion: Here we outline how understanding of shared pathways of aberrant BA homeostatic signaling may guide targeted therapies in some patients with IBS-D and subsets of patients with NAFLD.
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Affiliation(s)
- Michael J. Weaver
- Division of GastroenterologyWashington University School of MedicineSt. LouisMO
| | - Scott A. McHenry
- Division of GastroenterologyWashington University School of MedicineSt. LouisMO
| | - Gregory S. Sayuk
- Division of GastroenterologyWashington University School of MedicineSt. LouisMO
- U.S. Department of Veterans AffairsVA St. Louis Health Care SystemJohn Cochran DivisionSt. LouisMO
| | - C. Prakash Gyawali
- Division of GastroenterologyWashington University School of MedicineSt. LouisMO
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The efficacy and safety of probiotics in patients with irritable bowel syndrome: Evidence based on 35 randomized controlled trials. Int J Surg 2020; 75:116-127. [DOI: 10.1016/j.ijsu.2020.01.142] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 01/11/2020] [Accepted: 01/27/2020] [Indexed: 12/11/2022]
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Liu SB, Wang XS, Yue J, Yang L, Li XH, Hu LN, Lu JS, Song Q, Zhang K, Yang Q, Zhang MM, Bernabucci M, Zhao MG, Zhuo M. Cyclic AMP-dependent positive feedback signaling pathways in the cortex contributes to visceral pain. J Neurochem 2020; 153:252-263. [PMID: 31665810 DOI: 10.1111/jnc.14903] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 10/01/2019] [Accepted: 10/12/2019] [Indexed: 01/02/2023]
Abstract
Cortical areas including the anterior cingulate cortex (ACC) play critical roles in different types of chronic pain. Most of previous studies focus on the sensory inputs from somatic areas, and less information about plastic changes in the cortex for visceral pain. In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch-clamp recording, behavioral tests, western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out mice. Integrative approaches were used to investigate possible changes of neuronal AC1 in the ACC after the injury. We found that AC1, a key enzyme for pain-related cortical plasticity, was significantly increased in the ACC in an animal model of irritable bowel syndrome. Inhibiting AC1 activity by a selective AC1 inhibitor NB001 significantly reduced the up-regulation of AC1 protein in the ACC. Furthermore, we found that AC1 is required for NMDA GluN2B receptor up-regulation and increases of NMDA receptor-mediated currents. These results suggest that AC1 may form a positive regulation in the cortex during chronic visceral pain. Our findings demonstrate that the up-regulation of AC1 protein in the cortex may underlie the pathology of chronic visceral pain; and inhibiting AC1 activity may be beneficial for the treatment of visceral pain.
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Affiliation(s)
- Shui-Bing Liu
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.,Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Xin-Shang Wang
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Jiao Yue
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Le Yang
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Xu-Hui Li
- Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Li-Ning Hu
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Jing-Shan Lu
- Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Qian Song
- Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Kun Zhang
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Qi Yang
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Ming-Ming Zhang
- Department of Anatomy, Histology, Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an, China
| | - Matteo Bernabucci
- Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Ming-Gao Zhao
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China
| | - Min Zhuo
- Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China
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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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Heenan PE, Keenan JI, Bayer S, Simon M, Gearry RB. Irritable bowel syndrome and the gut microbiota. J R Soc N Z 2019. [DOI: 10.1080/03036758.2019.1695635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Phoebe E. Heenan
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | | | - Simone Bayer
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Myrthe Simon
- Department of Medicine, Vrije Universiteit, Amsterdam, Netherlands
| | - Richard B. Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
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Use of functional magnetic resonance imaging in patients with irritable bowel syndrome and functional dyspepsia. GASTROENTEROLOGY REVIEW 2019; 14:163-167. [PMID: 31649785 PMCID: PMC6807669 DOI: 10.5114/pg.2019.88163] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 05/14/2019] [Indexed: 12/13/2022]
Abstract
Functional brain imaging (positron emission tomography – PET, functional magnetic resonance imaging – fMRI), allowing in vivo analysis of the brain-digestive tract interaction and the neurological mechanisms underlying visceral hypersensitivity, significantly advanced research and helped in the understanding of the interrelations in this field. Differences in this parameter can result from alterations in task-related cognitive states or from resting state processes. Nowadays, advanced imaging techniques such as fMRI are more frequently used and are acknowledged among both clinicians and radiologists in the diagnostic algorithm of digestive tract diseases. Functional dyspepsia is a condition in which neuroimaging allows for analysis of dysfunctions within the brain-gut axis (BGA) engaged in processing of visceral discomfort and pain. The results of studies in patient groups with irritable bowel syndrome prove that psychosocial factors significantly affect the mechanisms regulating visceral sensitivity within the brain. The BGA includes neuronal pathways (autonomic nervous system), neuroendocrine (hypothalamo-pituitary-adrenal axis), and neuroimmunological ones. Psychological processes affect the functioning of the digestive system and can cause dyspeptic symptoms. A patient’s mental condition associated with stress can affect processes taking place in the central nervous system and trigger somatic reactions in the digestive tract through the autonomic visceral system.
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Weber Ii KA, Wager TD, Mackey S, Elliott JM, Liu WC, Sparks CL. Evidence for decreased Neurologic Pain Signature activation following thoracic spinal manipulation in healthy volunteers and participants with neck pain. NEUROIMAGE-CLINICAL 2019; 24:102042. [PMID: 31670070 PMCID: PMC6831903 DOI: 10.1016/j.nicl.2019.102042] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 09/18/2019] [Accepted: 10/17/2019] [Indexed: 12/19/2022]
Abstract
The use of brain-based models of pain were explored in two clinical studies. Neurologic pain signature activation decreased following spinal manipulation. Spinal manipulation altered the processing of pain-related brain activity. We provide evidence for a centrally mediated therapeutic action of spinal manipulation. Brain-based models have potential as objective clinical biomarkers of pain. Background Context Spinal manipulation (SM) is a common treatment for neck and back pain, theorized to mechanically affect the spine leading to therapeutic mechanical changes. The link between specific mechanical effects and clinical improvement is not well supported. SM's therapeutic action may instead be partially mediated within the central nervous system. Purpose To introduce brain-based models of pain for spinal pain and manual therapy research, characterize the distributed central mechanisms of SM, and advance the preliminary validation of brain-based models as potential clinical biomarkers of pain. Study Design Secondary analysis of two functional magnetic resonance imaging studies investigating the effect of thoracic SM on pain-related brain activity: A non-controlled, non-blinded study in healthy volunteers (Study 1, n = 10, 5 females, and mean age = 31.2 ± 10.0 years) and a randomized controlled study in participants with acute to subacute neck pain (Study 2, n = 24, 16 females, mean age = 38.0 ± 15.1 years). Methods Functional magnetic resonance imaging was performed during noxious mechanical stimulation of the right index finger cuticle pre- and post-intervention. The effect of SM on pain-related activity was studied within brain regions defined by the Neurologic Pain Signature (NPS) that are predictive of physical pain. Results In Study 1, evoked mechanical pain (p < 0.001) and NPS activation (p = 0.010) decreased following SM, and the changes in evoked pain and NPS activation were correlated (rRM2 = 0.418, p = 0.016). Activation within the NPS subregions of the dorsal anterior cingulate cortex (dACC, p = 0.012) and right secondary somatosensory cortex/operculum (rS2_Op, p = 0.045) also decreased following SM, and evoked pain was correlated with dACC activity (rRM2 = 0.477, p = 0.019). In Study 2, neck pain (p = 0.046) and NPS (p = 0.033) activation decreased following verum but not sham SM. Associations between evoked pain, neck pain, and NPS activation, were not significant and less clear, possibly due to inadequate power, methodological limitations, or other confounding factors. Conclusions The findings provide preliminary evidence that SM may alter the processing of pain-related brain activity within specific pain-related brain regions and support the use of brain-based models as clinical biomarkers of pain.
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Affiliation(s)
- Kenneth A Weber Ii
- Systems Neuroscience and Pain Lab, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA, United States.
| | - Tor D Wager
- Psychology and Neuroscience, Center for Neuroscience, Institute of Cognitive Science, University of Colorado Boulder, Boulder, CO, United States
| | - Sean Mackey
- Systems Neuroscience and Pain Lab, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA, United States
| | - James M Elliott
- Northern Sydney Local Health District, The Kolling Research Institute and The Faculty of Health Sciences, The University of Sydney, St. Leonards, NSW, Australia
| | - Wen-Ching Liu
- Center for Collaborative Brain Research, Department of Radiology, OSF HealthCare Saint Francis Medical Center, Peoria, IL, United States
| | - Cheryl L Sparks
- Center of Expertise, Rehabilitation and Occupational Health, OSF HealthCare, Peoria, IL, United States; School of Physical Therapy, South College, Knoxville, TN, United States
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Yi L, Sun H, Zhang H, Chen Y, Zhou L, Xuan L, Zhan T, Jiang Y, Xu S. Down-regulation of HTR1A-modulated ACC activation contributes to stress-induced visceral hyperalgesia in rats. Neurogastroenterol Motil 2019; 31:e13620. [PMID: 31121088 DOI: 10.1111/nmo.13620] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 04/07/2019] [Accepted: 04/24/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Long-term stress was suggested to cause visceral hypersensitivity and promote functional gastrointestinal disorders (FGIDs). Some brain regions such as the anterior cingulate cortex (ACC) may play an important role for generating visceral hypersensitivity; however, its molecular mechanisms are not clear. This study aimed to explore the role of 5-HT1A receptors (HTR1As) in activating ACC and corresponding mechanism, in stress-induced visceral hyperalgesia rats. METHODS The VH rat model was established by chronic water avoidance stress (WAS), and the visceral sensitivity was measured by electromyogram. Rat's anxiety-like behaviors were evaluated by the open field test (OFT) and elevated plus maze (EPM). To overexpress or down-regulate HTR1A expression, HTR1A-specific lentivirus expressing the green fluorescent protein was administered into the ACC. Protein expression levels were observed by Western blot. RESULTS The protein expression of HTR1A in bilateral ACC in WAS group was significantly lower than that in normal control (NC) and Sham-WAS groups, while the levels of c-fos in the ACC of WAS rats were significantly higher. Down-regulation of HTR1As could induce VH in control rats with the increased expression of c-fos, p-ERK, and p-Akt in ACC, while up-regulation of HTR1As in the ACC could partly inhibit ACC sensitization and stress-induced visceral hyperalgesia. CONCLUSIONS & INFERENCES Down-regulation of HTR1As modulates ACC activation probably through activating ERK and Akt pathways, thus contributes to the formation of stress-induced visceral hyperalgesia.
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Affiliation(s)
- Lisha Yi
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Huihui Sun
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Haiqin Zhang
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ying Chen
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lu Zhou
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liqian Xuan
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tingting Zhan
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuanxi Jiang
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shuchang Xu
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
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