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Fiúza-Fernandes J, Pereira-Mendes J, Esteves M, Radua J, Picó-Pérez M, Leite-Almeida H. Common neural correlates of chronic pain - A systematic review and meta-analysis of resting-state fMRI studies. Prog Neuropsychopharmacol Biol Psychiatry 2025; 138:111326. [PMID: 40086716 DOI: 10.1016/j.pnpbp.2025.111326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 02/20/2025] [Accepted: 03/05/2025] [Indexed: 03/16/2025]
Abstract
Maladaptive brain plasticity has been reported in chronic pain (CP) conditions, though it remains unclear if there are common alterations across pathologies. Therefore, we systematically synthesized literature comparing resting-state functional magnetic resonance imaging (rs-fMRI) in CP patients and healthy controls (HC), and meta-analyzed data whenever applicable. Separate meta-analyses were performed for each method - (fractional) amplitude of low-frequency fluctuations (fALFF, ALFF), regional homogeneity (ReHo), seed-based connectivity (according to the seed) and independent component analysis (according to the network). In qualitative synthesis, sensory-discriminative pain processing - thalamus, insula, temporal and sensory cortices - and cognitive and emotional processing - cingulate, prefrontal and parietal cortices and precuneus - regions concentrated CP/HC differences. Meta-analyses revealed decreased ALFF and increased ReHo in the precuneus, increased fALFF in the left posterior insula and disrupted within- and cross-network connectivity of default mode network (DMN) nodes, as well as altered connectivity in top-down pain modulation pathways. Specifically, it showed decreased anterior and increased posterior components' representation within DMN, enhanced connectivity between the medial prefrontal cortex (mPFC, part of the DMN) and anterior insula (part of the salience network), and decreased mPFC connectivity with the periaqueductal gray matter (PAG). Collectively, results suggest that CP disrupts the natural functional organization of the brain, particularly impacting DMN nodes (mPFC and precuneus), insula and top-town pain modulation circuits.
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Affiliation(s)
- Juliana Fiúza-Fernandes
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Joana Pereira-Mendes
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Madalena Esteves
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; Clinical Academic Center, Braga, Portugal
| | - Joaquim Radua
- Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain; Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Maria Picó-Pérez
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; Departamento de Psicología Básica, Clínica y Psicobiología, Universitat Jaume I, Castellón de la Plana, Spain
| | - Hugo Leite-Almeida
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; Clinical Academic Center, Braga, Portugal.
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Qiao Y, Lu H, Yang Y, Zang Y. Neuronal basis of high frequency fMRI fluctuation: direct evidence from simultaneous recording. Front Hum Neurosci 2024; 18:1501310. [PMID: 39545149 PMCID: PMC11560898 DOI: 10.3389/fnhum.2024.1501310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 10/17/2024] [Indexed: 11/17/2024] Open
Abstract
Resting-state functional magnetic resonance imaging (RS-fMRI) has been extensively utilized for noninvasive investigation of human brain activity. While studies employing simultaneous recordings of fMRI and electrophysiology have established a connection between the low-frequency fluctuation (< 0.1 Hz) observed in RS-fMRI and the local field potential (LFP), it remains unclear whether the RS-fMRI signal exhibits frequency-dependent modulation, which is a well-documented phenomenon in LFP. The present study concurrently recorded resting-state functional magnetic resonance imaging (RS-fMRI) and local field potentials (LFP) in the striatum of 8 rats before and after a pharmacological manipulation. We observed a highly similar frequency-dependent pattern of amplitude changes in both RS-fMRI and LFP following the manipulation, specifically an increase in high-frequency band amplitudes accompanied by a decrease in low-frequency band amplitudes. These findings provide direct evidence that the enhanced high-frequency fluctuations and reduced low-frequency fluctuations observed in RS-fMRI may reflect heightened neuronal activity.
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Affiliation(s)
- Yang Qiao
- Centre for Cognitive and Brain Sciences, University of Macau, Macao SAR, China
- Faculty of Health Sciences, University of Macau, Macao SAR, China
- Centre for Cognition and Brain Disorders/Department of Neurology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
- Institute of Psychological Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, Zhejiang, China
| | - Hanbing Lu
- Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MA, United States
| | - Yihong Yang
- Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MA, United States
| | - Yufeng Zang
- Centre for Cognition and Brain Disorders/Department of Neurology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
- Institute of Psychological Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, Zhejiang, China
- TMS Center, Deqing Hospital of Hangzhou Normal University, Huzhou, Zhejiang, China
- Collaborative Innovation Center of Hebei Province for Mechanism, Diagnosis and Treatment of Neuropsychiatric disease, Hebei Medical University, Shijiazhuang, Hebei, China
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Tiwari N, Qiao LY. Sex Differences in Visceral Pain and Comorbidities: Clinical Outcomes, Preclinical Models, and Cellular and Molecular Mechanisms. Cells 2024; 13:834. [PMID: 38786056 PMCID: PMC11119472 DOI: 10.3390/cells13100834] [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: 03/19/2024] [Revised: 05/03/2024] [Accepted: 05/10/2024] [Indexed: 05/25/2024] Open
Abstract
Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10-15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.
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Affiliation(s)
- Namrata Tiwari
- Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
- Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
| | - Liya Y. Qiao
- Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
- Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
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Yang L, He P, Zhang L, Li K. Altered resting-state brain functional activities and networks in Crohn's disease: a systematic review. Front Neurosci 2024; 18:1319359. [PMID: 38332859 PMCID: PMC10851432 DOI: 10.3389/fnins.2024.1319359] [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: 10/26/2023] [Accepted: 01/10/2024] [Indexed: 02/10/2024] Open
Abstract
Background Crohn's disease (CD) is a non-specific chronic inflammatory disease of the gastrointestinal tract and is a phenotype of inflammatory bowel disease (IBD). The current study sought to compile the resting-state functional differences in the brain between CD patients and healthy controls. Methods The online databases PubMed, Web of Science Core, and EMBASE were used to find the published neuroimage studies. The search period was from the beginning through December 15, 2023. The predetermined inclusion and exclusion criteria allowed for the identification of the studies. The studies were assembled by two impartial reviewers, who also assessed their quality and bias. Results This review comprised 16 resting-state fMRI studies in total. The included studies generally had modest levels of bias. According to the research, emotional processing and pain processing were largely linked to increased or decreased brain activity in patients with CD. The DMN, CEN, and limbic systems may have abnormalities in patients with CD, according to research on brain networks. Several brain regions showed functional changes in the active CD group compared to the inactive CD group and the healthy control group, respectively. The abnormalities in brain areas were linked to changes in mood fluctuations (anxiety, melancholy) in patients with CD. Conclusion Functional neuroimaging helps provide a better understanding of the underlying neuropathological processes in patients with CD. In this review, we summarize as follows: First, these findings indicate alterations in brain function in patients with CD, specifically affecting brain regions associated with pain, emotion, cognition, and visceral sensation; second, disease activity may have an impact on brain functions in patients with CD; and third, psychological factors may be associated with altered brain functions in patients with CD.
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Affiliation(s)
- Ling Yang
- Radiology Department, Chongqing General Hospital, Chongqing, China
- Department of Radiology Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Peipei He
- Radiology Department, Chongqing General Hospital, Chongqing, China
| | - Lingqin Zhang
- Radiology Department, Chongqing General Hospital, Chongqing, China
| | - Kang Li
- Radiology Department, Chongqing General Hospital, Chongqing, China
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Mayer EA, Ryu HJ, Bhatt RR. The neurobiology of irritable bowel syndrome. Mol Psychiatry 2023; 28:1451-1465. [PMID: 36732586 PMCID: PMC10208985 DOI: 10.1038/s41380-023-01972-w] [Citation(s) in RCA: 86] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/06/2023] [Accepted: 01/17/2023] [Indexed: 02/04/2023]
Abstract
Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of brain-gut microbiome interactions, starting with reported alterations in the gut connectome and enteric nervous system, and a list of distinct functional and structural brain signatures, and comparing them to the proposed brain alterations in anxiety disorders. We will then point out the emerging correlations between the brain networks with the genomic, gastrointestinal, immune, and gut microbiome-related parameters. We will incorporate this new information into a systems-based disease model of IBS. Finally, we will discuss the implications of such a model for the improved understanding of the disorder and the development of more effective treatment approaches in the future.
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Affiliation(s)
- Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Departments of Medicine, Psychiatry and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
| | - Hyo Jin Ryu
- A.T. Still University School of Osteopathic Medicine in Arizona, Meza, AZ, USA
| | - Ravi R Bhatt
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine at USC, University of Southern California, Los Angeles, CA, USA
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Sun Z, Wang X, Feng S, Xie C, Xing Y, Guo L, Zhao J, Ji C. A review of neuroendocrine immune system abnormalities in IBS based on the brain–gut axis and research progress of acupuncture intervention. Front Neurosci 2023; 17:934341. [PMID: 36968497 PMCID: PMC10034060 DOI: 10.3389/fnins.2023.934341] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 02/07/2023] [Indexed: 03/11/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common digestive disorder observed in clinics. Current studies suggest that the pathogenesis of the disease is closely related to abnormal brain–gut interactions, hypokinesia, visceral sensory hypersensitivity in the gastrointestinal tract, and alterations in the intestinal microenvironment. However, it is difficult for a single factor to explain the heterogeneity of symptoms. The Rome IV criteria emphasized the holistic biologic-psycho-social model of IBS, suggesting that symptoms of the disease are closely related to neurogastroenterology and various abnormalities in brain–gut interaction. This study comprehensively reviewed the relationship between the brain–gut axis and IBS, the structure of the brain–gut axis, and the relationship between the brain–gut axis and intestinal microenvironment, and discussed the relationship between the abnormal regulation of the nervous system, endocrine system, and immune system and the incidence of IBS on the basis of brain–gut axis. In terms of treatment, acupuncture therapy can regulate the neuroendocrine-immune system of the body and improve the intestinal microenvironment, and it has the advantages of safety, economy, and effectiveness. We study the pathogenesis of IBS from local to global and micro to macro, and review the use of acupuncture to treat the disease as a whole so as to provide new ideas for the treatment of the disease.
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Affiliation(s)
- Zhangyin Sun
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Xuejiao Wang
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Shangsheng Feng
- MOE Key Laboratory of Biomedical Information Engineering, Xi'an Jiaotong University, Xi'an, China
| | - Chaoju Xie
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Yu Xing
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Liang Guo
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Jingyu Zhao
- Department of Acupuncture and Moxibustion, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, China
- *Correspondence: Jingyu Zhao
| | - Changchun Ji
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
- Department of Acupuncture and Moxibustion, Shaanxi Provincial Institute of Traditional Chinese Medicine, Xi'an, China
- Changchun Ji
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Labus JS, Wang C, Mayer EA, Gupta A, Oughourlian T, Kilpatrick L, Tillisch K, Chang L, Naliboff B, Ellingson BM. Sex-specific brain microstructural reorganization in irritable bowel syndrome. Pain 2023; 164:292-304. [PMID: 35639426 PMCID: PMC9691795 DOI: 10.1097/j.pain.0000000000002699] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 05/17/2022] [Indexed: 02/06/2023]
Abstract
ABSTRACT Preliminary evidence suggests that there are sex differences in microstructural brain organization among individuals with irritable bowel syndrome (IBS). The aim of this study was to further investigate sex-dependent differences in brain microstructure and organization in a large sample of well-phenotyped participants with IBS compared with healthy controls. We hypothesized that female patients with IBS would show evidence for increased axonal strength and myelination within and between brain regions concerned with pain and sensory processing, when compared with males with IBS. We also hypothesized that female compared with male IBS subjects show greater levels of somatic awareness and sensory sensitivity consistent with multisystem sensory sensitivity. Diffusion tensor images and clinical assessments were obtained in 100 healthy controls (61 females) and 152 IBS (107 females) on a 3T Siemens Trio. Whole brain voxel-wise differences in fractional anisotropy, mean, radial and axial diffusivity, and track density as differences in somatic awareness and sensory sensitivity were assessed using the general linear model. Female compared with male IBS participants showed extensive microstructural alterations in sensorimotor, corticothalamic, and basal ganglia circuits involved in pain processing and integration of sensorimotor information. Together with the observed increases in symptom severity, somatic awareness, and sensory sensitivity, the findings support the hypotheses that the etiology and maintenance of symptoms in females with IBS may be driven by greater central sensitivity for multiple sensory stimuli.
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Affiliation(s)
- Jennifer S. Labus
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Chencai Wang
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Emeran A Mayer
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Arpana Gupta
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Talia Oughourlian
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Lisa Kilpatrick
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Kirsten Tillisch
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Lin Chang
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Bruce Naliboff
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Benjamin M. Ellingson
- Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
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Pei Y, Peng J, Zhang Y, Huang M, Zhou F. Aberrant functional connectivity and temporal variability of the dynamic pain connectome in patients with low back related leg pain. Sci Rep 2022; 12:6324. [PMID: 35428850 PMCID: PMC9012841 DOI: 10.1038/s41598-022-10238-4] [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: 08/09/2021] [Accepted: 03/23/2022] [Indexed: 11/17/2022] Open
Abstract
Neuroimaging studies have suggested a link between the intensity of chronic low back pain intensity and structural and functional brain alterations. However, chronic pain results from the coordination and dynamics among several brain networks that comprise the dynamic pain connectome. Here, we use resting-state functional magnetic resonance imaging and measures of static (sFC) and dynamic functional connectivity (dFC) variability in the typical (0.01–0.1 Hz) and five specific (slow-6 to slow-2) frequency bands to test hypotheses regarding disruption in this variability in low back-related leg pain (LBLP) patients who experience chronic pain and numbness. Twenty-four LBLP patients and 23 healthy controls completed clinical assessments, and partial correlational analyses between altered sFC and dFC variability and clinical measures were conducted. We found a lower within-network sFC in the ascending nociceptive pathway (Asc) and a lower cross-network sFC between nodes of the salience network and the Asc in the typical frequency band. In the slow-5 frequency band, a lower within-network sFC was found in the Asc. Abnormal cross-network sFC was found between nodes of the salience network-Asc (slow-5 and slow-6) and the default mode network-Asc (slow-4 and slow-6). Furthermore, cross-network abnormalities in the typical and certain specific frequency bands were linked to clinical assessments. These findings indicate that frequency-related within- and cross-network communication among the nodes in the dynamic pain connectome is dysfunctional in LBLP patients and that selecting specific frequencies may be potentially useful for detecting LBLP-related brain activity.
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Affiliation(s)
- Yixiu Pei
- Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People's Republic of China.,Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China.,Department of Medical Imaging, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, 341000, People's Republic of China
| | - Jidong Peng
- Department of Medical Imaging, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, 341000, People's Republic of China
| | - Yong Zhang
- Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Muhua Huang
- Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People's Republic of China.,Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China
| | - Fuqing Zhou
- Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People's Republic of China. .,Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China.
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9
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Su C, Liu W, Wang Q, Qiu S, Li M, Lv Y, Yu Y, Jia X, Li H. Abnormal resting-state local spontaneous functional activity in irritable bowel syndrome patients: A meta-analysis. J Affect Disord 2022; 302:177-184. [PMID: 35066011 DOI: 10.1016/j.jad.2022.01.075] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/01/2022] [Accepted: 01/18/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The current understanding of the pathogenesis underlying IBS is still unclear. Numerous studies have reported local abnormal resting state spontaneous functional activity in IBS patients in widespread brain regions. However, the results have not yet yielded consistent conclusions. Thus, we investigated common spontaneous functional activity abnormalities in patients with IBS by conducting a voxel-based meta-analysis. METHODS Up to December 2021, we performed a systematic search of IBS studies in five databases. These studies investigated the differences of resting state spontaneous brain activity between patients with IBS and healthy controls (HCs). The reference lists of included studies, relevant reviews and meta-analyses were investigated manually. Anisotropic effect-size signed differential mapping (AES-SDM) was applied in this meta-analysis. RESULTS Twelve studies encompassing 335 patients with IBS and 327 HCs were included in this meta-analysis. The local brain activities of the left calcarine fissure and surrounding cortex, right postcentral gyrus, left postcentral gyrus, left cerebellum, left inferior temporal gyrus, and left inferior frontal gyrus of triangular part in IBS patients were significantly increased compared with HCs, while the brain activities of the left anterior cingulate and paracingulate gyrus, right middle frontal gyrus, right supramarginal gyrus, left middle frontal gyrus, left precuneus, right putamen and right insula were significantly decreased compared with HCs. CONCLUSION The current study expands on a growing literature exploring resting state activity in IBS, which provides useful insights for understanding the underlying pathophysiology of nonorganic functional bowel disease and developing more targeted treatment and intervention strategies.
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Affiliation(s)
- Chang Su
- College of Teacher Education, Zhejiang Normal University, Jinhua, China; Key Laboratory of Intelligent Education Technology and Application, Zhejiang Normal University, Jinhua, China
| | - Wanlun Liu
- College of Teacher Education, Zhejiang Normal University, Jinhua, China
| | - Qianqian Wang
- College of Teacher Education, Zhejiang Normal University, Jinhua, China
| | - Shasha Qiu
- College of Teacher Education, Zhejiang Normal University, Jinhua, China; Key Laboratory of Intelligent Education Technology and Application, Zhejiang Normal University, Jinhua, China
| | - Mengting Li
- College of Teacher Education, Zhejiang Normal University, Jinhua, China
| | - Yating Lv
- Institute of Brain Science and Department of Psychology, School of Education, Hangzhou Normal University, Hangzhou, China; Center for Cognition and Brain Disorders, the Affiliated Hospital, Hangzhou Normal University, Hangzhou, China
| | - Yang Yu
- Department of Psychiatry, Second Affiliated Hospital, College of Medicine, Zhejiang University, China
| | - Xize Jia
- College of Teacher Education, Zhejiang Normal University, Jinhua, China.
| | - Huayun Li
- College of Teacher Education, Zhejiang Normal University, Jinhua, China; Key Laboratory of Intelligent Education Technology and Application, Zhejiang Normal University, Jinhua, China.
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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: 25] [Impact Index Per Article: 8.3] [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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11
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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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12
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Chernikova MA, Flores GD, Kilroy E, Labus JS, Mayer EA, Aziz-Zadeh L. The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder. Nutrients 2021; 13:nu13124497. [PMID: 34960049 PMCID: PMC8704412 DOI: 10.3390/nu13124497] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 12/13/2022] Open
Abstract
Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.
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Affiliation(s)
- Michelle A. Chernikova
- USC Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA 90033, USA; (M.A.C.); (G.D.F.); (E.K.)
- Brain and Creativity Institute, University of Southern California, Los Angeles, CA 90089, USA
- Psychology Department, Loyola Marymount University, Los Angeles, CA 90045, USA
| | - Genesis D. Flores
- USC Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA 90033, USA; (M.A.C.); (G.D.F.); (E.K.)
- Brain and Creativity Institute, University of Southern California, Los Angeles, CA 90089, USA
- Psychology Department, California State Polytechnic University, Pomona, CA 91768, USA
| | - Emily Kilroy
- USC Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA 90033, USA; (M.A.C.); (G.D.F.); (E.K.)
- Brain and Creativity Institute, University of Southern California, Los Angeles, CA 90089, USA
| | - Jennifer S. Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA 90095, USA;
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA 90095, USA
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- Gonda (Goldschmied) Neuroscience and Genetics Research Center, Brain Research Institute UCLA, Los Angeles, CA 90095, USA
| | - Emeran A. Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles, Los Angeles, CA 90095, USA;
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA 90095, USA
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- Correspondence: (E.A.M.); (L.A.-Z.)
| | - Lisa Aziz-Zadeh
- USC Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA 90033, USA; (M.A.C.); (G.D.F.); (E.K.)
- Brain and Creativity Institute, University of Southern California, Los Angeles, CA 90089, USA
- Correspondence: (E.A.M.); (L.A.-Z.)
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13
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Yang L, Yan Y, Li Y, Hu X, Lu J, Chan P, Yan T, Han Y. Frequency-dependent changes in fractional amplitude of low-frequency oscillations in Alzheimer's disease: a resting-state fMRI study. Brain Imaging Behav 2021; 14:2187-2201. [PMID: 31478145 DOI: 10.1007/s11682-019-00169-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly individuals. We conducted this study to examine whether alterations in the fractional amplitudes of low-frequency fluctuations (fALFF) in the AD spectrum were frequency-dependent and symptom-relevant. A total of 43 patients with subjective cognitive decline (SCD), 52 with amnestic mild cognitive impairment (aMCI), 44 with Alzheimer's dementia (d-AD) and 55 well-matched controls participated in resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitudes were measured using fALFF within the slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. Repeated-measures analysis of variance was performed on fALFF within two bands and correlated with neuropsychological test scores. The significant main effects of frequency and group on fALFF differed widely across brain regions. There were more varied areas in the slow-5 band than the slow-4 band. The fALFF associated with primary disease effects was mainly distributed in the parietal lobe. Obvious frequency band and group interaction effects were observed in the left angular gyrus, left calcarine fissure and surrounding cortex, left superior cerebellum, left cuneus and right lingual gyrus. Neuropsychological tests scores were significantly correlated with the fALFF magnitude of the left cuneus and right lingual in the slow-5 band. Our results suggested that the AD continuum had abnormal amplitudes in intrinsic brain activity, and these abnormalities were frequency-dependent and mainly associated with the slow-5 band rather than the slow-4 band. This may guide the frequency choice of future rs-fMRI studies and provide new insights into the neuropathophysiology of AD.
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Affiliation(s)
- Liu Yang
- Department of Neurology, Xuanwu Hospital of Capital Medical University, No.45 Street Changchun, District Xichen, Beijing, 100053, China
| | - Yan Yan
- School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081, China
| | - Yuxia Li
- Department of Neurology, Xuanwu Hospital of Capital Medical University, No.45 Street Changchun, District Xichen, Beijing, 100053, China
| | - Xiaochen Hu
- Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany
| | - Jie Lu
- Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Piu Chan
- Department of Neurology, Xuanwu Hospital of Capital Medical University, No.45 Street Changchun, District Xichen, Beijing, 100053, China.,Beijing Institute of Geriatrics, Beijing, China.,National Clinical Research Center for Geriatric Disorders, Beijing, China
| | - Tianyi Yan
- School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081, China.
| | - Ying Han
- Department of Neurology, Xuanwu Hospital of Capital Medical University, No.45 Street Changchun, District Xichen, Beijing, 100053, China. .,Beijing Institute of Geriatrics, Beijing, China. .,National Clinical Research Center for Geriatric Disorders, Beijing, China. .,Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China.
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14
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Duan S, Liu L, Li G, Wang J, Hu Y, Zhang W, Tan Z, Jia Z, Zhang L, von Deneen KM, Zhang Y, Nie Y, Cui G. Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation. Front Neurosci 2021; 15:628880. [PMID: 33776637 PMCID: PMC7991789 DOI: 10.3389/fnins.2021.628880] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 02/01/2021] [Indexed: 12/12/2022] Open
Abstract
Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)-rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex-rACC, PreCen-aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN-SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.
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Affiliation(s)
- Shijun Duan
- Department of Radiology, Tangdu Hospital, Air Force Medical University, Xi’an, China
| | - Lei Liu
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Guanya Li
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Jia Wang
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Yang Hu
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Wenchao Zhang
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Zongxin Tan
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Zhenzhen Jia
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Lei Zhang
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Karen M. von Deneen
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Yi Zhang
- Center for Brain Imaging, School of Life Sciences and Technology, Xidian University, Xi’an, China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an, China
| | - Guangbin Cui
- Department of Radiology, Tangdu Hospital, Air Force Medical University, Xi’an, China
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15
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Yang S, Boudier-Revéret M, Choo YJ, Chang MC. Association between Chronic Pain and Alterations in the Mesolimbic Dopaminergic System. Brain Sci 2020; 10:701. [PMID: 33023226 PMCID: PMC7600461 DOI: 10.3390/brainsci10100701] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 09/23/2020] [Accepted: 09/28/2020] [Indexed: 12/15/2022] Open
Abstract
Chronic pain (pain lasting for >3 months) decreases patient quality of life and even occupational abilities. It can be controlled by treatment, but often persists even after management. To properly control pain, its underlying mechanisms must be determined. This review outlines the role of the mesolimbic dopaminergic system in chronic pain. The mesolimbic system, a neural circuit, delivers dopamine from the ventral tegmental area to neural structures such as the nucleus accumbens, prefrontal cortex, anterior cingulate cortex, and amygdala. It controls executive, affective, and motivational functions. Chronic pain patients suffer from low dopamine production and delivery in this system. The volumes of structures constituting the mesolimbic system are known to be decreased in such patients. Studies on administration of dopaminergic drugs to control chronic pain, with a focus on increasing low dopamine levels in the mesolimbic system, show that it is effective in patients with Parkinson's disease, restless legs syndrome, fibromyalgia, dry mouth syndrome, lumbar radicular pain, and chronic back pain. However, very few studies have confirmed these effects, and dopaminergic drugs are not commonly used to treat the various diseases causing chronic pain. Thus, further studies are required to determine the effectiveness of such treatment for chronic pain.
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Affiliation(s)
- Seoyon Yang
- Department of Rehabilitation Medicine, Ewha Woman’s University Seoul Hospital, Ewha Woman’s University School of Medicine, Seoul 07804, Korea;
| | - Mathieu Boudier-Revéret
- Department of Physical Medicine and Rehabilitation, Centre Hospitalier de l’Université de Montréal, Montreal, QC H2W 1T8, Canada;
| | - Yoo Jin Choo
- Production R&D Division Advanced Interdisciplinary Team, Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Deagu 41061, Korea;
| | - Min Cheol Chang
- Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu 42415, Korea
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16
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Abstract
Arrhythmic fluctuations in neural activity occur at many levels of the nervous system. Such activity does not have a characteristic temporal periodicity but can exhibit statistical similarities, most commonly power-law scaling behavior, which is indicative of scale-free dynamics. The recurrence of scaling laws across many different systems and its manifestation in behavior has prompted a search for unifying principles in human brain function. With this in mind, a focused search for abnormities in scale-free dynamics is of considerable clinical relevance to migraine and other clinical pain disorders. Here, we examined the scale-free properties of the resting-state functional magnetic resonance imaging (fMRI) signal in the broadband frequency range known to be related to spontaneous neural activity (0.01-0.1 Hz). In a large cohort of episodic migraine patients (N = 40), we observed that the strength of long-range temporal correlations in the fMRI signal (captured by the scaling exponent α) was significantly higher in the sensorimotor network compared with healthy controls. Increases in the scaling exponent were positively correlated with fMRI signal variance and negatively correlated with the patient's self-reported headache intensity. These changes in the fMRI signal suggest that the temporal structure of amplitude fluctuations carries valuable information about the dynamic state of the underlying neuronal networks and ensuing sensory impairments in migraine. The demonstrated scaling laws pose a novel quantitative approach for examining clinically relevant interindividual variability in migraine and other pain disorders.
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17
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Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome. Pain 2020; 160:2004-2012. [PMID: 31045748 PMCID: PMC6727903 DOI: 10.1097/j.pain.0000000000001589] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstrate altered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However, alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changes remain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthy controls [HC]) with respect to aINS glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations and addressed possible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonance spectroscopy of bilateral aINS to assess Glx and GABA+ concentrations. Questionnaire data from all participants and prospective symptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related and psychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P < 0.05, right aINS P < 0.001), whereas no group differences were detected for GABA+ concentrations. Lower right-lateralized Glx concentrations in patients were substantially predicted by longer pain duration, while less frequent use of adaptive pain-coping predicted lower Glx in left aINS. Our findings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results also indicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and of the left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.
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18
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Kano M, Grinsvall C, Ran Q, Dupont P, Morishita J, Muratsubaki T, Mugikura S, Ly HG, Törnblom H, Ljungberg M, Takase K, Simrén M, Van Oudenhove L, Fukudo S. Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis. Sci Rep 2020; 10:11015. [PMID: 32620938 PMCID: PMC7335204 DOI: 10.1038/s41598-020-67048-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 05/27/2020] [Indexed: 01/14/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.
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Affiliation(s)
- Michiko Kano
- Sukawa clinic, Kirari health coop, Fukushima, Japan.
- Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan.
- Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan.
| | - Cecilia Grinsvall
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Qian Ran
- Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium
| | - Patrick Dupont
- Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium
| | - Joe Morishita
- Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Tomohiko Muratsubaki
- Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Shunji Mugikura
- Diagnostic Radiology, Tohoku University Hospital, Sendai, Japan
| | - Huynh Giao Ly
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Hans Törnblom
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Maria Ljungberg
- Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Medical Physics and Biomedical Engineering, Diagnostic Imaging, Sahlgrenska University Hospital, MR Centre, Gothenburg, Sweden
| | - Kei Takase
- Diagnostic Radiology, Tohoku University Hospital, Sendai, Japan
| | - Magnus Simrén
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Cognitive and Affective Neuroscience Lab, Department of Psychological & Brain Sciences, Dartmouth College, Hanover, NH, USA
| | - Shin Fukudo
- Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan
- Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan
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19
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The medial temporal lobe in nociception: a meta-analytic and functional connectivity study. Pain 2020; 160:1245-1260. [PMID: 30747905 DOI: 10.1097/j.pain.0000000000001519] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recent neuroimaging studies implicate the medial temporal lobe (MTL) in nociception and pain modulation. Here, we aim to identify which subregions of the MTL are involved in human pain and to test its connectivity in a cohort of chronic low-back pain patients (CBP). We conducted 2 coordinate-based meta-analyses to determine which regions within the MTL showed consistent spatial patterns of functional activation (1) in response to experimental pain in healthy participants and (2) in chronic pain compared with healthy participants. We followed PRISMA guidelines and performed activation likelihood estimate (ALE) meta-analyses. The first meta-analysis revealed consistent activation in the right anterior hippocampus (right antHC), parahippocampal gyrus, and amygdala. The second meta-analysis revealed consistently less activation in patients' right antHC, compared with healthy participants. We then conducted a seed-to-voxel resting state functional connectivity of the right antHC seed with the rest of the brain in 77 CBP and 79 age-matched healthy participants. We found that CBP had significantly weaker antHC functional connectivity to the medial prefrontal cortex compared with healthy participants. Taken together, these data indicate that the antHC has abnormally lower activity in chronic pain and reduced connectivity to the medial prefrontal cortex in CBP. Future studies should investigate the specific role of the antHC in the development and management of chronic pain.
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20
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Kang J, Lee SH, Lee JW, Jang DK, Choi JH, Choi YH, Paik WH, Ahn DW, Jeong JB, Ryu JK, Kim YT. Impact of balloon inflation on the insertion of endoscopic ultrasound: a prospective, randomized controlled trial. Endosc Int Open 2020; 8:E458-E464. [PMID: 32140561 PMCID: PMC7055621 DOI: 10.1055/a-1096-0438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 12/02/2019] [Indexed: 11/19/2022] Open
Abstract
Background and study aims During endoscopic ultrasound (EUS), patients may experience severe discomfort. The radial echoendoscope has a balloon around its tip. Balloon inflation prior to insertion may reduce contact injury and pharyngeal pain. The purpose of this study was to investigate the effect of balloon inflation on pharyngeal pain during insertion. Patients and methods Patients who underwent radial EUS for pancreatobiliary disease were randomized into standard insertion or balloon-inflated insertion. The primary outcome was the proportion of moderate-to-severe pharyngeal pain. Secondary outcomes were the degree of pharyngeal pain, risk factors for moderate pharyngeal pain, procedure-related adverse events, and pharyngeal pain depending on the experience of the endoscopist. Results A total of 481 patients were randomized into two groups: standard insertion (238) and balloon inflation (243). No statistically significant differences in proportion of moderate-to-severe pain were found (26.5 % vs. 20.2 %, P = 0.107). Balloon inflation (HR 0.65; 95 % CI (0.42-0.98, P = 0.041) was a protective factor against moderate pain. Balloon inflation reduced the proportion of patients with moderate-to-severe pain when performed by physicians with less than 3months of experience with EUS (44.7 % vs. 25.3 %, P = 0.012). Conclusion Balloon inflation did not reduce the absolute degree of post-procedural pain with EUS, but it reduced the number of patients with moderate-to-severe pain when performed by physicians with less than 3 months of experience.
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Affiliation(s)
- Jinwoo Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea,Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Woo Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea,Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, Korea
| | - Dong Kee Jang
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea,Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jin Ho Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Young Hoon Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea,Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong-Won Ahn
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea,Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Ji Bong Jeong
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea,Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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21
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Zheng P, Jia S, Guo D, Chen S, Zhang W, Cheng A, Xie W, Sun G, Leng J, Lang J. Central Sensitization-Related Changes in Brain Function Activity in a Rat Endometriosis-Associated Pain Model. J Pain Res 2020; 13:95-107. [PMID: 32021399 PMCID: PMC6968808 DOI: 10.2147/jpr.s232313] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 12/17/2019] [Indexed: 12/31/2022] Open
Abstract
Background Pain sensitization processing in the central nervous system may be related to endometriosis-associated pain in patients. The purpose of this study was to understand the alterations in the abnormal pain response in central brain areas and explore the central sensitization mechanism of endometriosis-associated pain. Methods An endometriosis model was established in 40 Sprague-Dawley rats, and the rats underwent pain model assessment through behavioral tests. Twenty Sprague-Dawley rats underwent a sham operation as the control group. Thirteen pain rats and 8 control rats received Rs-fMRI examination to explore the brain functional activity areas, and the regional homogeneity (ReHo) method was used to analyze relevant functional signals among the whole brain. The states of neurons and expression of TRPV1 and NMDRA located in the abnormal ReHo signal brain regions were observed using Nissl staining, qRT-PCR and immunohistochemistry. Results The rats were divided into a pain group and a control group based on the different syndromes and behavioral assessments. We detected significant enhancement of ReHo signals in the anterior cingulate cortex, hippocampus, and thalamus and a reduction in the ReHo values in the basomedial amygdaloid nucleus (BM) and primary motor cortex (M1) in the pain rat group via Rs-fMRI examination. The number of Nissl bodies and apoptotic neurons was increased; moreover, the volume of neurons increased compensatorily in the cingulate cortex, thalamus and hippocampus in the pain group. TRPV1 and NMDRA were overexpressed in apoptotic neurons in the higher ReHo value brain regions in the endometriosis pain group. Conclusion These findings suggest that in rats with endometriosis-associated pain, ReHo signal enhancement was observed in the cingulate cortex, thalamus and hippocampus, which may be due to the increase in the number of apoptotic neurons or the compensatory increase in the volume of overactive neurons.
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Affiliation(s)
- Ping Zheng
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
| | - Shuangzheng Jia
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
| | - Dalong Guo
- Air Force Medical Center, PLA, Beijing, People's Republic of China
| | - Sikai Chen
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
| | - Wen Zhang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
| | - Aoshuang Cheng
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
| | - Weijie Xie
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, People's Republic of China
| | - Guibo Sun
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, People's Republic of China
| | - Jinhua Leng
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
| | - Jinghe Lang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China
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22
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Serafini RA, Pryce KD, Zachariou V. The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities. Biol Psychiatry 2020; 87:64-73. [PMID: 31806085 PMCID: PMC6954000 DOI: 10.1016/j.biopsych.2019.10.018] [Citation(s) in RCA: 159] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 10/24/2019] [Accepted: 10/25/2019] [Indexed: 12/18/2022]
Abstract
Chronic pain is a complex neuropsychiatric disorder characterized by sensory, cognitive, and affective symptoms. Over the past 2 decades, researchers have made significant progress toward understanding the impact of mesolimbic dopamine circuitry in acute and chronic pain. These efforts have provided insights into the circuits and intracellular pathways in the brain reward center that are implicated in sensory and affective manifestations of chronic pain. Studies have also identified novel therapeutic targets as well as factors that affect treatment responsiveness. Dysregulation of dopamine function in the brain reward center may further promote comorbid mood disorders and vulnerability to addiction. This review discusses recent clinical and preclinical findings on the neuroanatomical and neurochemical adaptations triggered by prolonged pain states in the brain reward pathway. Furthermore, this discussion highlights evidence of mechanisms underlying comorbidities among pain, depression, and addiction.
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Affiliation(s)
- Randal A Serafini
- Nash Family Department of Neuroscience, Department of Pharmacological Sciences, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Kerri D Pryce
- Nash Family Department of Neuroscience, Department of Pharmacological Sciences, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Venetia Zachariou
- Nash Family Department of Neuroscience, Department of Pharmacological Sciences, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
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23
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Mayer EA, Labus J, Aziz Q, Tracey I, Kilpatrick L, Elsenbruch S, Schweinhardt P, Van Oudenhove L, Borsook D. Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report. Gut 2019; 68:1701-1715. [PMID: 31175206 PMCID: PMC6999847 DOI: 10.1136/gutjnl-2019-318308] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/18/2019] [Accepted: 03/24/2019] [Indexed: 12/12/2022]
Abstract
Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
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Affiliation(s)
- Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Jennifer Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Qasim Aziz
- Neurogastroenterology Group, Queen Mary University of London, London, UK
| | - Irene Tracey
- Departments of Anaesthetics and Clinical Neurology, Pembroke College, Oxford, UK
| | - Lisa Kilpatrick
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Sigrid Elsenbruch
- Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg, Duisburg, Germany
| | | | - Lukas Van Oudenhove
- Translational Research in GastroIntestinal Disorders, KU Leuven Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium
| | - David Borsook
- Center for Pain and the Brain, Boston Children's, Massachusetts General and McLean Hospitals, Harvard Medical School, Boston, Massachusetts, USA
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24
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Holly LT, Wang C, Woodworth DC, Salamon N, Ellingson BM. Neck disability in patients with cervical spondylosis is associated with altered brain functional connectivity. J Clin Neurosci 2019; 69:149-154. [PMID: 31420276 DOI: 10.1016/j.jocn.2019.08.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 08/04/2019] [Indexed: 12/12/2022]
Abstract
Cervical degenerative disease is a major cause of neck disability, but it has been understudied in patients with cervical spondylotic (CS), largely due to the fact that the neurological impairment associated with this condition tends to be the primary treatment focus. This observational study examined the cerebral functional alterations occurring in advanced cervical spondylosis and myelopathy using resting state functional MRI. Associations between functional connectivity (FC) and neck disability using the Neck Disability Index (NDI) were assessed. Results of the study demonstrated an increase in FC with increasing in neck disability in regions associated with sensorimotor system (both postcentral gyri and precentral gyri, bilaterally, with the SMA; bilateral precentral gyri and the left postcentral gyrus, with the left superior frontal gyrus; bilateral SMA and the left putamen, with the superior frontal gyri). Accounting for the difference in neurological function (mJOA score), strong connectivity between the precentral gyri and the SMA associated with the neck disability. Consistent with studies in chronic pain conditions, these findings suggest neck disability is associated with altered cerebral FC in cervical spondylosis patients.
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Affiliation(s)
- Langston T Holly
- Dept. of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Chencai Wang
- Dept. of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Davis C Woodworth
- Dept. of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Noriko Salamon
- Dept. of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Benjamin M Ellingson
- Dept. of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; Physics and Biology in Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States; Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States.
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25
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Rodiño-Janeiro BK, Pardo-Camacho C, Santos J, Martínez C. Mucosal RNA and protein expression as the next frontier in IBS: abnormal function despite morphologically intact small intestinal mucosa. Am J Physiol Gastrointest Liver Physiol 2019; 316:G701-G719. [PMID: 30767681 DOI: 10.1152/ajpgi.00186.2018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Irritable bowel syndrome (IBS) is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very complex and varied array of observations indicating the presence of structural and molecular abnormalities underlying characteristic motor and sensitive changes and clinical manifestations. Analysis of gene and protein expression in the intestinal mucosa has shed light on the molecular mechanisms implicated in IBS physiopathology. This analysis uncovers constitutive and inductive genetic and epigenetic marks in the small and large intestine that highlight the role of epithelial barrier, immune activation, and mucosal processing of foods and toxins and several new molecular pathways in the origin of IBS. The incorporation of innovative high-throughput techniques into IBS research is beginning to provide new insights into highly structured and interconnected molecular mechanisms modulating gene and protein expression at tissue level. Integration and correlation of these molecular mechanisms with clinical and environmental data applying systems biology/medicine and data mining tools emerge as crucial steps that will allow us to get meaningful and more definitive comprehension of IBS-detailed development and show the real mechanisms and causality of the disease and the way to identify more specific diagnostic biomarkers and effective treatments.
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Affiliation(s)
- Bruno Kotska Rodiño-Janeiro
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca , Barcelona , Spain.,Department of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (Facultat de Medicina) , Barcelona , Spain
| | - Cristina Pardo-Camacho
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca , Barcelona , Spain.,Department of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (Facultat de Medicina) , Barcelona , Spain
| | - Javier Santos
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca , Barcelona , Spain.,Department of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (Facultat de Medicina) , Barcelona , Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas , Madrid , Spain
| | - Cristina Martínez
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca , Barcelona , Spain.,Department of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (Facultat de Medicina) , Barcelona , Spain
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26
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Jin Q, Duan S, Li G, Sun L, Hu Y, Hu C, Zhao J, von Deneen KM, Qian L, Wang H, Ji G, Wu K, Fan D, Cui G, Nie Y, Zhang Y. Sex-related differences in resting-state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation. Neurogastroenterol Motil 2019; 31:e13566. [PMID: 30729624 DOI: 10.1111/nmo.13566] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 11/28/2018] [Accepted: 01/13/2019] [Indexed: 02/06/2023]
Abstract
Functional magnetic resonance imaging (fMRI) has been used to investigate sex-related differences in brain abnormalities in patients with irritable bowel syndrome (IBS). Like IBS, women with functional constipation (FC) are 2.1 times as many as men. No study has been performed yet to examine sex-related differences in brain activity and connectivity in patients with FC. Here, we employed resting-state fMRI with amplitude of low-frequency fluctuation (ALFF) to investigate brain functional differences in 51 patients with FC (34 females) and 52 healthy controls (34 females). Results showed abdominal pain and abdominal distension correlated with trait (TAI) and state (SAI) anxiety ratings in the female FC group, and abdominal distension correlated with sensation of incomplete evacuation in the male FC group. Two-way ANOVA revealed sex effects on ALFF in precentral gyrus, thalamus, insula (INS), and orbital frontal cortex (OFC, PFWE < 0.05). Post hoc test showed that the female FC group had lower ALFF than males in these brain regions (P < 0.01), and ALFF in INS and OFC was correlated with abdominal pain and difficulty of defecation, respectively. Seed voxel correlation analysis showed that the female FC group had weaker connectivity than males between INS and lateral OFC (lOFC). INS-lOFC connectivity was negatively correlated with the anxiety score in the female FC group and was negatively correlated with abdominal distension in the male FC group. These findings provide the first insight into sex-related differences in patients with FC and highlight that INS and OFC play an important role in modulating the intrinsic functional connectivity of the resting brain network showing that this role is influenced by sex.
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Affiliation(s)
- Qingchao Jin
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Shijun Duan
- Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Guanya Li
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Lijuan Sun
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Yang Hu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Chunxin Hu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Jizheng Zhao
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
- College of Mechanical and Electronic Engineering, Northwest A&F University, Yangling, China
| | - Karen M von Deneen
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Long Qian
- Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Huaning Wang
- Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Gang Ji
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Guangbin Cui
- Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Yi Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China
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27
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Zhou F, Zhao Y, Zhu L, Jiang J, Huang M, Zhang Y, Zhuang Y, Gong H. Compressing the lumbar nerve root changes the frequency-associated cerebral amplitude of fluctuations in patients with low back/leg pain. Sci Rep 2019; 9:2246. [PMID: 30783132 PMCID: PMC6381144 DOI: 10.1038/s41598-019-38721-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 01/08/2019] [Indexed: 12/19/2022] Open
Abstract
Understanding the central mechanisms responsible for lumbar nerve root compression may facilitate the development of new therapeutic strategies. In this study, our aim was to investigate the amplitude of fluctuations (AF) in five specific frequency bands and the full-frequency band realm to provide novel insight into the rhythm of the neuronal activity of low back/leg pain (LBLP) patients (n = 25). Compared with healthy controls, LBLP patients exhibited a significantly altered AF in multiple brain regions, including the right or left middle and inferior temporal gyri, bilateral precuneus, right anterior insula/frontal operculum, right or left inferior parietal lobule/postcentral gyrus, and other locations at five specific frequencies (P < 0.01, with Gaussian random field theory correction). Trends of an increase and a decrease in the AF in pain- and sensory-related regions, respectively, were also observed from low to high frequencies (Bonferroni-corrected α level of P < 0.05/84). In addition, in the bilateral rectal gyrus, a significant association was identified between the AF in the five specific frequency bands and disease status (P < 0.05). These findings suggest that in LBLP patients, intrinsic functional plasticity related to low back pain, leg pain and numbness affects the AF of the pain matrix and sensory-processing regions in both low- and high-frequency bands.
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Affiliation(s)
- Fuqing Zhou
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, People's Republic of China. .,Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China.
| | - Yanlin Zhao
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, People's Republic of China.,Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China
| | - Li Zhu
- School of Information Engineering, Nanchang University, Nanchang, 330031, People's Republic of China
| | - Jian Jiang
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, People's Republic of China.,Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China
| | - Muhua Huang
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, People's Republic of China.,Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China
| | - Yong Zhang
- Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, 330006, People's Republic of China.
| | - Ying Zhuang
- Department of Oncology, The Second Hospital of Nanchang, Nanchang, 330003, People's Republic of China
| | - Honghan Gong
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, People's Republic of China.,Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People's Republic of China
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28
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Zhou F, Wu L, Guo L, Zhang Y, Zeng X. Local connectivity of the resting brain connectome in patients with low back-related leg pain: A multiscale frequency-related Kendall's coefficient of concordance and coherence-regional homogeneity study. NEUROIMAGE-CLINICAL 2019; 21:101661. [PMID: 30677731 PMCID: PMC6348392 DOI: 10.1016/j.nicl.2019.101661] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 12/30/2018] [Accepted: 01/04/2019] [Indexed: 01/25/2023]
Abstract
Increasing evidence has suggested that central plasticity plays a crucial role in the development and maintenance of (chronic) nonspecific low back pain. However, it is unclear how local or short-distance functional interactions contribute to persisting low back-related leg pain (LBLP) due to a specific condition (i.e., lumbar disc herniation). In particular, the multiscale nature of local connectivity properties in various brain regions is still unclear. Here, we used voxelwise Kendall's coefficient of concordance (KCC) and coherence (Cohe) regional homogeneity (ReHo) in the typical (0.01–0.1 Hz) and five specific frequency (slow-6 to slow-2) bands to analyze individual whole-brain resting-state functional magnetic resonance imaging scans in 25 persistent LBLP patients (duration: 36.7 ± 9.6 months) and 26 healthy control subjects. Between-group differences demonstrated significant alterations in the KCC- and Cohe- ReHo of the right cerebellum posterior lobe, brainstem, left medial prefrontal cortex and bilateral precuneus in LBLP patients in the typical and five specific frequency bands, respectively, along with interactions between disease status and the five specific frequency bands in several regions of the pain matrix and the default-mode network (P < .01, Gaussian random field theory correction). The altered ReHo in the five specific frequency bands was correlated with the duration of pain and two-point discrimination, which were assessed using partial correlational analysis. These results linked the course of disease to the local connectivity properties in specific frequency bands in persisting LBLP. In future studies exploring local connectome association in pain conditions, integrated frequency bands and analytical methods should be considered.
This study demonstrated significant interactions between disease status and five specific frequency bands in several regions. The alterations in ReHo of five specific frequency bands were related to the duration of disease and 2-PD in LBLP patients. It is useful to select specific frequency or the method of analyses to improve the detection of LBLP-related brain activity.
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Affiliation(s)
- Fuqing Zhou
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China; Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, China.
| | - Lin Wu
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China; Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, China
| | - Linghong Guo
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China; Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, China
| | - Yong Zhang
- Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, China.
| | - Xianjun Zeng
- Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China; Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, China
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Camps G, de Graaf K, Smeets PAM. Men and Women Differ in Gastric Fluid Retention and Neural Activation after Consumption of Carbonated Beverages. J Nutr 2018; 148:1976-1983. [PMID: 30517723 DOI: 10.1093/jn/nxy230] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 08/17/2018] [Indexed: 12/19/2022] Open
Abstract
Background The most commonly consumed carbonated beverages are soda and beer. Carbon dioxide increases gastric volume, which can lead to epigastric discomfort. Women are more susceptible to this; however, correlations with neural activity and gastric distention are unknown. Objective This study sought to determine the subjective, gastric, and neural correlates of epigastric discomfort in men and women. Methods Thirty-four healthy, normal-weight adults [17 women; mean ± SD body mass index (BMI; kg/m2): 22.3 ± 1.9; 17 men; BMI: 22.8 ± 1.8] participated in a randomized crossover study with 2 treatments: ingestion of 500 mL beer or soda. Before and after consumption, gastric content and brain activity were measured with magnetic resonance imaging (MRI). Participants rated fullness, bloating, hunger, and nausea at baseline and at t = 0, 10, 20, and 30 min together with gastric MRI. Brain activity [cerebral blood flow (CBF)] was measured at baseline and at t = 5 and 35 min. Liquid, gas, and total gastric volume (TGV) were segmented from gastric MRI. Ratings and gastric content areas under the curve (AUCs) were tested with a mixed model with sex and drink as factors. Results For subjective ratings, only nausea in the beer condition scored significantly greater for women (9.4-point increase; P = 0.045). Liquid stomach content was significantly greater for women (2525 mL × min increase; P = 0.019). In both men and women, the strongest correlation for bloating was with TGV (r = 0.45, P < 0.01) and for nausea was with the liquid fraction AUC (r = 0.45, P < 0.01). CBF changes did not differ between the drinks. Men showed greater CBF than women in the left precentral and postcentral gyri at t = 5 min. Conclusions There are differences between sexes when it comes to appetite ratings, gastric fluid retention, and neural activation. Discomfort in women may be related to fluid rather than gas in the stomach, because they retain more fluid than men. Differences between men and women should be considered when studying digestion. This study was registered with the Dutch Trial Registry as NTR5418 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5418).
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Affiliation(s)
- Guido Camps
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
| | - Kees de Graaf
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
| | - Paul A M Smeets
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands.,Image Sciences Institute, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
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Kano M, Dupont P, Aziz Q, Fukudo S. Understanding Neurogastroenterology From Neuroimaging Perspective: A Comprehensive Review of Functional and Structural Brain Imaging in Functional Gastrointestinal Disorders. J Neurogastroenterol Motil 2018; 24:512-527. [PMID: 30041284 PMCID: PMC6175554 DOI: 10.5056/jnm18072] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 05/21/2018] [Indexed: 12/13/2022] Open
Abstract
This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state.
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Affiliation(s)
- Michiko Kano
- Frontier Research Institute for Interdisciplinary Sciences (FRIS), Tohoku University, Sendai,
Japan
- Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai,
Japan
- Psychosomatic Medicine, Tohoku University Hospital, Sendai,
Japan
| | | | - Qasim Aziz
- Center for Digestive Diseases, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London,
UK
| | - Shin Fukudo
- Behavioral Medicine, Graduate School of Medicine, Tohoku University, Sendai,
Japan
- Psychosomatic Medicine, Tohoku University Hospital, Sendai,
Japan
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Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach. J Neurosci 2018; 38:7293-7302. [PMID: 30012686 DOI: 10.1523/jneurosci.0578-18.2018] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 05/18/2018] [Accepted: 07/06/2018] [Indexed: 12/20/2022] Open
Abstract
Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain.SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.
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Hippocampal gene expression profiling in a rat model of functional constipation reveals abnormal expression genes associated with cognitive function. Neurosci Lett 2018; 675:103-109. [DOI: 10.1016/j.neulet.2018.03.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 02/08/2018] [Accepted: 03/12/2018] [Indexed: 12/29/2022]
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Sari S, Kozanhan B, Egilmez AI, Soyder A, Aydin ON, Galimberti F, Sessler D, Turan A. The influence of the menstrual cycle on acute and persistent pain after laparoscopic cholecystectomy. Braz J Anesthesiol 2018. [PMID: 29373141 PMCID: PMC9391774 DOI: 10.1016/j.bjane.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Affiliation(s)
- Sinem Sari
- Adnan Menderes University Medical Faculty, Department of Anesthesiology and Reanimation, Aydin, Turquia
| | - Betul Kozanhan
- University of Health Sciences, Konya Education and Research Hospital, Department of Anesthesiology and Reanimation, Konya, Turquia.
| | - Ayse Ilksen Egilmez
- University of Health Sciences, Konya Education and Research Hospital, Department of Anesthesiology and Reanimation, Konya, Turquia
| | - Aykut Soyder
- Adnan Menderes University Medical Faculty, Department of General Surgery, Aydin, Turquia
| | - Osman Nuri Aydin
- Adnan Menderes University Medical Faculty, Department of Anesthesiology and Reanimation, Aydin, Turquia
| | - Fabrizio Galimberti
- Cleveland Clinic Lerner College of Medicine, Cleveland, OH, Estados Unidos da América
| | - Daniel Sessler
- Cleveland Clinic, Department of Outcomes Research, Cleveland, OH, Estados Unidos da América
| | - Alparslan Turan
- Cleveland Clinic, Department of Outcomes Research, Cleveland, OH, Estados Unidos da América
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Dai YJ, Zhang X, Yang Y, Nan HY, Yu Y, Sun Q, Yan LF, Hu B, Zhang J, Qiu ZY, Gao Y, Cui GB, Chen BL, Wang W. Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures. J Headache Pain 2018. [PMID: 29541875 PMCID: PMC5852124 DOI: 10.1186/s10194-018-0849-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Methods Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Results Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. Conclusion In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. Trial registration ClinicalTrials.gov, NCT02820974. Registered 28 June 2016.
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Affiliation(s)
- Yu-Jie Dai
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China.,Department of Obstetrics and Gynecology, Xijing Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 15 West Changle Road, Xi'an, Shaanxi Province, 710032, China.,Department of Clinical Nutrition, Xijing Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 15 West Changle Road, Xi'an, Shaanxi Province, 710032, China
| | - Xin Zhang
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Yang Yang
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Hai-Yan Nan
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Ying Yu
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Qian Sun
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Lin-Feng Yan
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Bo Hu
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Jin Zhang
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China
| | - Zi-Yu Qiu
- Student Brigade, the Military Medical University of PLA Airforce (Fourth Military Medical University), 169 West Changle Road, Xi'an, Shaanxi Province, 710032, China
| | - Yi Gao
- Student Brigade, the Military Medical University of PLA Airforce (Fourth Military Medical University), 169 West Changle Road, Xi'an, Shaanxi Province, 710032, China
| | - Guang-Bin Cui
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China.
| | - Bi-Liang Chen
- Department of Obstetrics and Gynecology, Xijing Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 15 West Changle Road, Xi'an, Shaanxi Province, 710032, China.
| | - Wen Wang
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, the Military Medical University of PLA Airforce (Fourth Military Medical University), 569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China.
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Gupta A, Woodworth DC, Ellingson BM, Rapkin AJ, Naliboff B, Kilpatrick LA, Stains J, Masghati S, Tillisch K, Mayer EA, Labus JS. Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia. THE JOURNAL OF PAIN 2018; 19:528.e1-528.e15. [PMID: 29391213 DOI: 10.1016/j.jpain.2017.12.269] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 11/06/2017] [Accepted: 12/17/2017] [Indexed: 12/13/2022]
Abstract
Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. PERSPECTIVE Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system.
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Affiliation(s)
- Arpana Gupta
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Davis C Woodworth
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Benjamin M Ellingson
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Department of Radiology at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Andrea J Rapkin
- Department of Obstetrics and Gynecology at UCLA, Los Angeles, California
| | - Bruce Naliboff
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Lisa A Kilpatrick
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Jean Stains
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California
| | - Salome Masghati
- Department of Obstetrics and Gynecology at UCLA, Los Angeles, California
| | - Kirsten Tillisch
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Jennifer S Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California.
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Nan J, Zhang L, Chen Q, Zong N, Zhang P, Ji X, Ma S, Zhang Y, Huang W, Du Z, Xia Y, Zhang M. White Matter Microstructural Similarity and Diversity of Functional Constipation and Constipation-predominant Irritable Bowel Syndrome. J Neurogastroenterol Motil 2018; 24:107-118. [PMID: 29291612 PMCID: PMC5753909 DOI: 10.5056/jnm17038] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 05/24/2017] [Accepted: 08/16/2017] [Indexed: 12/21/2022] Open
Abstract
Background/Aims The Rome III criteria separated chronic constipation into functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C), but some researchers questioned the partitioning and treated both as distinct parts of a continuum. The study aims to explore the similarity and diversity of brain white matter between FC and IBS-C. Methods The voxel-wise analysis of the diffusion parameters was used to quantify the white matter changes of female brains in 18 FC patients and 20 IBS-C patients compared with a comparison group with 19 healthy controls by tract-based spatial statistics. The correlations between diffusive parameters and clinical symptoms were evaluated using a Pearson's correlation. Results In comparison to healthy controls, FC patients showed a decrease of fractional anisotropy (FA) and an increase of radial diffusivity (RD) in multiple major fibers encompassing the corpus callosum (CC, P = 0.001 at peak), external capsule (P = 0.002 at peak), corona radiata (CR, P = 0.001 at peak), and superior longitudinal fasciculus (SLF, P = 0.002 at peak). In contrast, IBS-C patients showed FA and RD aberrations in the CC (P = 0.048 at peak). Moreover, the direct comparison between FC and IBS-C showed only RD differences in the CR and SLF. In addition, FA and RD in the CC were significantly associated with abdominal pain for all patients, whereas FA in CR (P = 0.016) and SLF (P = 0.040) were significantly associated with the length of time per attempt and incomplete evacuation separately for FC patients. Conclusion These results may improve our understanding of the pathophysiological mechanisms underlying different types of constipation.
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Affiliation(s)
- Jiaofen Nan
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Liangliang Zhang
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Qiqiang Chen
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Nannan Zong
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Peiyong Zhang
- First Affiliated Hospital of Xinxiang Medical University, Weihui, China
| | - Xing Ji
- First Affiliated Hospital of Yan'an University, Yan'an, China
| | - Shaohui Ma
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yuchen Zhang
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wei Huang
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Zhongzhou Du
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Yongquan Xia
- School of Computer and Communication Engineering, Zhengzhou University of Light Industry, Zhengzhou, China
| | - Ming Zhang
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Sari S, Kozanhan B, Egilmez AI, Soyder A, Aydin ON, Galimberti F, Sessler D, Turan A. [The influence of the menstrual cycle on acute and persistent pain after laparoscopic cholecystectomy]. Rev Bras Anestesiol 2018; 68:231-237. [PMID: 29373141 DOI: 10.1016/j.bjan.2017.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Accepted: 11/08/2017] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Fluctuations of female sex hormones during menstrual cycle influence pain perception. Endogenous pain inhibition is impaired in follicular phase of menstrual cycle. We tested the primary hypothesis that the women having surgery during their follicular phase have more acute pain and require higher opioids than those in the luteal phase, and secondarily we tested that women who have surgery during their follicular phase have more incisional pain at 3 month postoperatively. METHODS 127 adult females having laparoscopic cholecystectomy were randomized to have surgery during the luteal or follicular phase of their menstrual cycle. Standardized anesthesia and pain management regimen was given to all patients. Pain and analgesic consumption were evaluated in post-anesthesia care unit and every 4h in the first 24h. Adverse effects were questioned every 4h. Time to oral intake and ambulation were recorded. Post-surgical pain, hospital anxiety, depression scale, SF-12 questionnaire were evaluated at 1 and 3 month visits. RESULTS There was no difference in acute pain scores and analgesic consumption through the 24h period, Visual Analog Scale at 24h was 1.5±1.5cm for follicular group 1.4±1.7cm for luteal group (p=0.57). Persistent postoperative pain was significantly more common one and at three month, with an incidence was 33% and 32% in the patients at follicular phase versus 16% and 12% at luteal phase, respectively. The Visual Analog Scale at one and at three month was 1.6±0.7cm and 1.8±0.8cm for follicular group and 2.7±1.3cm and 2.9±1.7cm in the luteal group (p=0.02), respectively. There were no significant differences between the groups with respect to anxiety and depression, SF-12 scores at either time. Nausea was more common in follicular-phase group (p=0.01) and oral feeding time was shorter in follicular phase (5.9±0.9h) than in luteal phase (6.8±1.9h, p=0.02). CONCLUSIONS Although persistent postoperative pain was significantly more common one and three months after surgery the magnitude of the pain was low. Our results do not support scheduling operations to target particular phases of the menstrual cycle.
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Affiliation(s)
- Sinem Sari
- Adnan Menderes University Medical Faculty, Department of Anesthesiology and Reanimation, Aydin, Turquia
| | - Betul Kozanhan
- University of Health Sciences, Konya Education and Research Hospital, Department of Anesthesiology and Reanimation, Konya, Turquia.
| | - Ayse Ilksen Egilmez
- University of Health Sciences, Konya Education and Research Hospital, Department of Anesthesiology and Reanimation, Konya, Turquia
| | - Aykut Soyder
- Adnan Menderes University Medical Faculty, Department of General Surgery, Aydin, Turquia
| | - Osman Nuri Aydin
- Adnan Menderes University Medical Faculty, Department of Anesthesiology and Reanimation, Aydin, Turquia
| | - Fabrizio Galimberti
- Cleveland Clinic Lerner College of Medicine, Cleveland, OH, Estados Unidos da América
| | - Daniel Sessler
- Cleveland Clinic, Department of Outcomes Research, Cleveland, OH, Estados Unidos da América
| | - Alparslan Turan
- Cleveland Clinic, Department of Outcomes Research, Cleveland, OH, Estados Unidos da América
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Evaluation of Chronic Pain Using Magnetic Resonance (MR) Neuroimaging Approaches: What the Clinician Needs to Know. Clin J Pain 2017; 33:281-290. [PMID: 27518493 DOI: 10.1097/ajp.0000000000000415] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Numerous neuroimaging techniques have been recently used to investigate central mechanisms involved in pain perception and to examine morphological and functional brain alterations associated with chronic pain. Compared to self-reporting approaches, objective imaging techniques are expected to potentially lead to better pain assessment and guide management. This comprehensive scoping review aims to identify recent magnetic resonance imaging (MRI) approaches that have been used to characterize the brain of chronic pain subjects, using structural, chemical and functional MRI techniques. METHODS A systematic search and review of the literature was conducted and the resultant studies were critically examined for relevance. RESULTS MRI neuroimaging of various chronic pain conditions were summarized. We classified the collected studies into: structural brain alterations, VBM (voxel based morphology) examination of structural changes, DTI, changes in brain chemistry, functional and blood flow brain alterations. DISCUSSION From our clinical experience, we have noted that most clinicians are not aware of the capabilities of advanced MRI methods in assessing cortical manifestations of chronic pain. In addition, many clinicians are not aware of the cortical alterations present in individuals with chronic pain. This comprehensive scoping review thus sets out to first summarize MRI neuroimaging techniques that are available in the current literature to examine chronic pain. We then identify cortical MR approaches that have been able to reliably predict transition from acute to chronic pain. Finally, we summarize MRI neuroimaging techniques that have been used to track treatment response of individuals with chronic pain.
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Intrinsic brain abnormalities in irritable bowel syndrome and effect of anxiety and depression. Brain Imaging Behav 2017; 10:1127-1134. [PMID: 26556814 DOI: 10.1007/s11682-015-9478-1] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated intrinsic brain abnormalities in irritable bowel syndrome (IBS) and effect of anxiety and depression. Thirty IBS patients and 31 matched healthy controls underwent rs-fMRI scanning. Regional brain activity was evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and compared between IBS patients and healthy controls with a two-sample t-test. Areas with abnormal ALFF were further used as seeds in subsequent inter-regional functional connectivity (FC) analysis. Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect. Compared to healthy controls, IBS patients showed decreased ALFF in several core default mode network regions (medial prefrontal cortex [MPFC], posterior cingulate cortex [PCC], bilateral inferior parietal cortices [IPC]), and in middle frontal cortex, right orbital part of the superior frontal gyrus (ORBsup), dorsal anterior cingulate cortex (dACC), and ventral anterior cingulated cortex (vACC), while they showed increased ALFF in bilateral posterior insula and cuneus. In addition, IBS patients revealed decreased inter-regional positive FC between MPFC and right ORBsup, between vACC and PCC, as well as decreased negative FC between MPFC and left posterior insula, while they showed increased negative FC between MPFC and cuneus. The inclusion of anxiety and depression as covariates abolished ALFF differences in dACC and vACC, but none of the FC differences. IN CONCLUSION IBS patients had disturbed intrinsic brain function. High levels of anxiety and depression in IBS patients could account for their decreased intrinsic brain activity in regions (the ACC) involved in affective processing.
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Abstract
Epidemiological studies indicate sex-related differences among functional gastrointestinal disorders (FGIDs) wherein females are more likely to receive a diagnosis than their male counterparts. However, the mechanism by which females exhibit an increased vulnerability for development of these pathophysiologies remains largely unknown, and therapeutic treatments are limited. The current chapter focuses on clinical research outlining our current knowledge of factors that contribute to the female predominance among FGID patients such as the menstrual cycle and sex hormones. In addition, we will discuss progress in preclinical research, including animal models, which serve as valuable tools for the investigation of the development and long term manifestation of symptoms observed within the patient population. Although much progress has been made, additional longitudinal studies in both clinical and preclinical research are necessary to identify more specific mechanisms underlying sex-related differences in FGIDs as well as targets for improved therapeutic approaches.
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Guleria A, Karyampudi A, Singh R, Khetrapal CL, Verma A, Ghoshal UC, Kumar D. Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging. J Neurogastroenterol Motil 2017; 23:415-427. [PMID: 28192648 PMCID: PMC5503292 DOI: 10.5056/jnm16148] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 12/25/2016] [Accepted: 12/26/2016] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. Methods Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. Results IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. Conclusions Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain.
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Affiliation(s)
- Anupam Guleria
- Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India
| | - Arun Karyampudi
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Rajan Singh
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Chunni L Khetrapal
- Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India
| | - Abhai Verma
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Dinesh Kumar
- Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India
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Increased Amplitude of Thalamocortical Low-Frequency Oscillations in Patients with Migraine. J Neurosci 2017; 36:8026-36. [PMID: 27466345 DOI: 10.1523/jneurosci.1038-16.2016] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 06/16/2016] [Indexed: 01/11/2023] Open
Abstract
UNLABELLED For many years, neurobiological theories have emphasized the importance of neuronal oscillations in the emergence of brain function. At the same time, clinical studies have shown that disturbances or irregularities in brain rhythms may relate to various common neurological conditions, including migraine. Increasing evidence suggests that the CNS plays a fundamental role in the predisposition to develop different forms of headache. Here, we present human imaging data that strongly support the presence of abnormal low-frequency oscillations (LFOs) in thalamocortical networks of patients in the interictal phase of migraine. Our results show that the main source of arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus. In addition, spontaneous LFOs in the thalamus were selectively associated with the headache attack frequency, meaning that the varying amplitude of dysrhythmia could predispose patients to recurrent attacks. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability. We further speculate that the intrinsic dynamics of thalamocortical network oscillations are crucial for early sensory processing and therefore could underlie important pathophysiological processes involved in multisensory integration. SIGNIFICANCE STATEMENT In many cases, migraine attacks are thought to begin centrally. A major obstacle to studying intrinsic brain activity has been the identification of the precise anatomical structures and functional networks that are involved in migraine. Here, we present imaging data that strongly support the presence of abnormal low-frequency oscillations in thalamocortical networks of patients in the interictal phase of migraine. This arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus and was selectively associated with headache attack frequency. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability and higher-level processes involved in multisensory integration.
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Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome. NEUROIMAGE-CLINICAL 2017. [PMID: 28649489 PMCID: PMC5470568 DOI: 10.1016/j.nicl.2017.06.001] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N = 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.
Functional connectivity (FC) was compared between hyper- and normosensitive IBS. Hypersensitive IBS showed enhanced salience and sensorimotor network FC. Normosensitive IBS had decreased amygdala and anterior insula FC within the DMN. Changes in FC were associated with visceral sensitivity and symptom severity. Altered FC may play a key role in hypervigilance and hyperalgesia in IBS.
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Lee IS, Preissl H, Enck P. How to Perform and Interpret Functional Magnetic Resonance Imaging Studies in Functional Gastrointestinal Disorders. J Neurogastroenterol Motil 2017; 23:197-207. [PMID: 28256119 PMCID: PMC5383114 DOI: 10.5056/jnm16196] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 12/19/2016] [Indexed: 12/20/2022] Open
Abstract
Functional neuroimaging studies have revealed the importance of the role of cognitive and psychological factors and the dysregulation of the brain-gut axis in functional gastrointestinal disorder patients. Although only a small number of neuroimaging studies have been conducted in functional gastrointestinal disorder patients, and despite the fact that the neuroimaging technique requires a high level of knowledge, the technique still has a great deal of potential. The application of functional magnetic resonance imaging (fMRI) technique in functional gastrointestinal disorders should provide novel methods of diagnosing and treating patients. In this review, basic knowledge and technical/practical issues of fMRI will be introduced to clinicians.
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Affiliation(s)
- In-Seon Lee
- Psychosomatic Medicine and Psychotherapy Department, University of Tübingen, Tübingen, Germany.,Graduate Training Centre of Neuroscience, International Max Planck Research School, University of Tübingen, Tübingen, Germany
| | - Hubert Preissl
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.,Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany
| | - Paul Enck
- Psychosomatic Medicine and Psychotherapy Department, University of Tübingen, Tübingen, Germany
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Malfliet A, Coppieters I, Van Wilgen P, Kregel J, De Pauw R, Dolphens M, Ickmans K. Brain changes associated with cognitive and emotional factors in chronic pain: A systematic review. Eur J Pain 2017; 21:769-786. [DOI: 10.1002/ejp.1003] [Citation(s) in RCA: 204] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/02/2016] [Indexed: 11/08/2022]
Affiliation(s)
- A. Malfliet
- Department of Physiotherapy, Human Physiology and Anatomy (KIMA); Faculty of Physical Education and Physiotherapy; Vrije Universiteit Brussels; Belgium
- Pain in Motion International Research Group; Brussels Belgium
- Department of Physical Medicine and Physiotherapy; University Hospital Brussels; Belgium
- Department of Rehabilitation Sciences and Physiotherapy; Faculty of Medicine and Health Sciences; Ghent University; Belgium
| | - I. Coppieters
- Pain in Motion International Research Group; Brussels Belgium
- Department of Rehabilitation Sciences and Physiotherapy; Faculty of Medicine and Health Sciences; Ghent University; Belgium
| | - P. Van Wilgen
- Department of Physiotherapy, Human Physiology and Anatomy (KIMA); Faculty of Physical Education and Physiotherapy; Vrije Universiteit Brussels; Belgium
- Pain in Motion International Research Group; Brussels Belgium
- Transcare; Transdisciplinary Pain Management Centre; Groningen The Netherlands
| | - J. Kregel
- Pain in Motion International Research Group; Brussels Belgium
- Department of Rehabilitation Sciences and Physiotherapy; Faculty of Medicine and Health Sciences; Ghent University; Belgium
| | - R. De Pauw
- Department of Rehabilitation Sciences and Physiotherapy; Faculty of Medicine and Health Sciences; Ghent University; Belgium
| | - M. Dolphens
- Department of Rehabilitation Sciences and Physiotherapy; Faculty of Medicine and Health Sciences; Ghent University; Belgium
| | - K. Ickmans
- Department of Physiotherapy, Human Physiology and Anatomy (KIMA); Faculty of Physical Education and Physiotherapy; Vrije Universiteit Brussels; Belgium
- Pain in Motion International Research Group; Brussels Belgium
- Department of Physical Medicine and Physiotherapy; University Hospital Brussels; Belgium
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Yu CX, Ji TT, Song H, Li B, Han Q, Li L, Zhuo ZZ. Abnormality of spontaneous brain activities in patients with chronic neck and shoulder pain: A resting-state fMRI study. J Int Med Res 2017; 45:182-192. [PMID: 28222620 PMCID: PMC5536581 DOI: 10.1177/0300060516679345] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Objectives Chronic gneck and shoulder pain (CNSP) is a common clinical symptom of cervical spondylotic radiculopathy. Several studies using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that most chronic pain diseases are accompanied by structural and functional changes in the brain. However, few rs-fMRI studies have examined CNSP. The current study investigated cerebral structural and functional changes in CNSP patients. Methods In total, 25 CNSP patients and 20 healthy volunteers participated in the study. 3D-T1W and rs-fMRI images were acquired. Voxel-based morphometry analysis was applied to structural images, and regional homogeneity (ReHo) was extracted from rs-fMRI. Statistical analysis was performed on post-processing images and ReHo parameter maps. Results The results revealed no significant differences in brain structure between the two groups. In the patient group, ReHo values were significantly increased in the bilateral middle frontal gyrus and decreased in the left insula, superior frontal gyrus, middle cingulate gyrus, supplementary motor area, right postcentral gyrus, and superior parietal lobule. Conclusions This initial structural and rs-fMRI study of CNSP revealed characteristic features of spontaneous brain activity of CNSP patients. These findings may be helpful for increasing our understanding of the neuropathology of CNSP.
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Affiliation(s)
- Cheng-Xin Yu
- 1 Department of Radiology, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei, China
| | - Ting-Ting Ji
- 1 Department of Radiology, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei, China
| | - Hao Song
- 1 Department of Radiology, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei, China
| | - Bo Li
- 1 Department of Radiology, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei, China
| | - Qiang Han
- 1 Department of Radiology, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei, China
| | - Liang Li
- 1 Department of Radiology, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei, China
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Differences in regional homogeneity between patients with Crohn's disease with and without abdominal pain revealed by resting-state functional magnetic resonance imaging. Pain 2017; 157:1037-1044. [PMID: 26761381 DOI: 10.1097/j.pain.0000000000000479] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Abnormal pain processing in the central nervous system may be related to abdominal pain in patients with Crohn's disease (CD). The purpose of this study was to investigate changes in resting-state brain activity in patients with CD in remission and its relationship with the presence of abdominal pain. Twenty-five patients with CD and with abdominal pain, 25 patients with CD and without abdominal pain, and 32 healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. Regional homogeneity (ReHo) was used to assess resting-state brain activity. Daily pain scores were collected 1 week before functional magnetic resonance imaging. We found that patients with abdominal pain exhibited lower ReHo values in the insula, middle cingulate cortex (MCC), and supplementary motor area and higher ReHo values in the temporal pole. In contrast, patients without abdominal pain exhibited lower ReHo values in the hippocampal/parahippocampal cortex and higher ReHo values in the dorsomedial prefrontal cortex (all P < 0.05, corrected). The ReHo values of the insula and MCC were significantly negatively correlated with daily pain scores for patients with abdominal pain (r = -0.53, P = 0.008 and r = -0.61, P = 0.002, respectively). These findings suggest that resting-state brain activities are different between remissive patients with CD with and without abdominal pain and that abnormal activities in insula and MCC are closely related to the severity of abdominal pain.
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Gupta A, Mayer EA, Fling C, Labus JS, Naliboff BD, Hong JY, Kilpatrick LA. Sex-based differences in brain alterations across chronic pain conditions. J Neurosci Res 2017; 95:604-616. [PMID: 27870423 PMCID: PMC5120652 DOI: 10.1002/jnr.23856] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 06/18/2016] [Accepted: 07/06/2016] [Indexed: 12/17/2022]
Abstract
Common brain mechanisms are thought to play a significant role across a multitude of chronic pain syndromes. In addition, there is strong evidence for the existence of sex differences in the prevalence of chronic pain and in the neurobiology of pain. Thus, it is important to consider sex when developing general principals of pain neurobiology. The goal of the current Mini-Review is to evaluate what is known about sex-specific brain alterations across multiple chronic pain populations. A total of 15 sex difference and 143 single-sex articles were identified from among 412 chronic pain neuroimaging articles. Results from sex difference studies indicate more prominent primary sensorimotor structural and functional alterations in female chronic pain patients compared with male chronic pain patients: differences in the nature and degree of insula alterations, with greater insula reactivity in male patients; differences in the degree of anterior cingulate structural alterations; and differences in emotional-arousal reactivity. Qualitative comparisons of male-specific and female-specific studies appear to be consistent with the results from sex difference studies. Given these differences, mixed-sex studies of chronic pain risk creating biased data or missing important information and single-sex studies have limited generalizability. The advent of large-scale neuroimaging databases will likely aid in building a more comprehensive understanding of sex differences and commonalities in brain mechanisms underlying chronic pain. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Arpana Gupta
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Emeran A Mayer
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Department of Psychiatry, UCLA, Los Angeles, CA, USA
- Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, USA
| | - Connor Fling
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
| | - Jennifer S Labus
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Department of Psychiatry, UCLA, Los Angeles, CA, USA
- Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, USA
| | - Bruce D Naliboff
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Jui-Yang Hong
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Lisa A Kilpatrick
- Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Pain and Interoception Network (PAIN), UCLA, Los Angeles, CA, USA
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Walitt B, Ceko M, Gracely JL, Gracely RH. Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature. Curr Rheumatol Rev 2016; 12:55-87. [PMID: 26717948 DOI: 10.2174/1573397112666151231111104] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 06/24/2015] [Accepted: 12/29/2015] [Indexed: 12/14/2022]
Abstract
Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and nonpainful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.
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Affiliation(s)
- Brian Walitt
- National Center for Complementary and Integrative Health, National Institutes of Health, 10 Center Drive, Bethesda, MD 20814, USA.
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