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Alihosseini S, Khodaei F, Jaberinezhad M, Azari M, Ezzati Khatab M, Akhlaghi H, Ghanini N, Tarzamni MK, Eghbali E. Evaluation of gallbladder contractility and Doppler findings in patients with irritable bowel syndrome; a case-control study. Scand J Gastroenterol 2024; 59:344-351. [PMID: 38031926 DOI: 10.1080/00365521.2023.2287989] [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: 09/05/2023] [Revised: 10/12/2023] [Accepted: 11/21/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder causing abdominal pain, altered bowel habits and bloating without structural issues. Gallbladder dysfunction may be linked to IBS due to disrupted cholecystokinin release. This study aims to assess gallbladder function and related hemodynamic parameters using Doppler ultrasound in IBS before and after meals. METHOD In this case-control study, we investigated gallbladder function differences between constipation-predominant IBS (C-IBS) patients and healthy volunteers. Participants underwent ultrasonography to measure gallbladder parameters before and after consuming a predefined meal. Gallbladder volume, wall thickness and resistance index (RI) of cystic and superior mesenteric arteries (SMA) were assessed. Student t-test and paired t-test were used to compare case and control groups and pre- and post-meal data, respectively. RESULTS A total of 34 people (18 C-IBS and 16 healthy control) were included. The mean (Standard deviation) of gallbladder fasting volume was measured 24.74 (8.85) and 29.73 (9.65) cubic millimeter for case and controls, respectively. Postprandial volume was 11.34 (5.66) and 16.9 (6.16) cubic millimeter for case and controls respectively. We observed a statistically significant difference in emptying fractions (EF) between groups (p value = 0.009). IBS patients had a smaller fasting SMA RI (p value = 0.016) but the fraction of change after meal was not significant (p value = 0.10). The cystic artery RI did not reach statistical significance between the fasting and post-meal values (p value = 0.067). CONCLUSION IBS patients have a higher emptying fraction and lower change in SMA RI compared to healthy controls. Further studies with larger sample size, inclusion of patients with different coexisting conditions and subtypes of IBS and combining colon transit study with gallbladder ejection fraction evaluation can be used to further provide more meaning to this study.
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Affiliation(s)
- Samin Alihosseini
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Farzaneh Khodaei
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Mehran Jaberinezhad
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Mojtaba Azari
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Maghsoud Ezzati Khatab
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Hedieh Akhlaghi
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Nima Ghanini
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Mohammad Kazem Tarzamni
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
| | - Elham Eghbali
- Medical Radiation Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, The Islamic Republic of Iran
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Kumari MV, Amarasiri L, Rajindrajith S, Devanarayana NM. Functional abdominal pain disorders and asthma: two disorders, but similar pathophysiology? Expert Rev Gastroenterol Hepatol 2021; 15:9-24. [PMID: 32909837 DOI: 10.1080/17474124.2020.1821652] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 09/07/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Functional abdominal pain disorders (FAPDs) and asthma are common ailments affecting both children and adults worldwide. Multiple studies have demonstrated an association between these two disorders. However, the exact reason for this observed association is not apparent. AREAS COVERED The current review has explored available literature and outlined multiple underlying pathophysiological mechanisms, common to both asthma and FAPDs, as possible reasons for this association. EXPERT OPINION Smooth muscle dysfunction, hypersensitivity and hyper-responsiveness, mucosal inflammation, and barrier dysfunction involving gastrointestinal and respiratory tracts are the main underlying pathophysiological mechanisms described for the generation of symptoms in FAPDs and asthma. In addition, alterations in neuroendocrine regulatory functions, immunological dysfunction, and microbial dysbiosis have been described in both disorders. We believe that the pathophysiological processes that were explored in this article would be able to expand the mechanisms of the association. The in-depth knowledge is needed to be converted to therapeutic and preventive strategies to improve the quality of care of children suffering from FAPDs and asthma.
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Affiliation(s)
- Manori Vijaya Kumari
- Department of Physiology, Faculty of Medicine & Allied Sciences, Rajarata University of Sri Lanka , Anuradhapura, Sri Lanka
| | - Lakmali Amarasiri
- Department of Physiology, Faculty of Medicine, University of Colombo , Colombo, Sri Lanka
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Bachani P, Kumar L, Kumar N, Memon MK, Memon S, Irfan S, Alam O, Kumar B. Prevalence and Symptom Characteristics of Irritable Bowel Syndrome Among Bronchial Asthma Patients in Pakistan. Cureus 2020; 12:e12231. [PMID: 33500855 PMCID: PMC7819454 DOI: 10.7759/cureus.12231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that leads to a variety of symptoms including abdominal discomfort and change in stool frequency and consistency. Asthma is a common disease of the airway. Some studies have suggested that a relationship between IBS and asthma exist, while others have contradicted the claim. This study aims to determine the prevalence of IBS in asthmatic patients and compare their symptoms with symptoms of IBS patients in non-asthmatic patients. METHODOLOGY In this case-control study, 100 known and documented asthmatic patients were included as cases, and 100 non-asthmatic healthy patients were included as controls from July to August 2019. These patients were given a questionnaire based on ROME II criteria for the diagnosis of IBS. Prevalence and symptoms of IBS were compared between cases and controls. A probability level, P < 0.05 was considered significant. Result: IBS was found in 41 out of 100 asthma patients (41%) and 18 out of 100 controls (18%) with a P-value of 0.0005 and was more common in females in both asthmatic (63.41%) and non-asthmatic patients (66.66%). Symptoms such as abdominal pain/distress (63.41% vs. 11.11%, P-value: 0.0013) and bloating (82.92% vs. 33.33%, P-value: 0.0005) were significantly higher in asthmatic patient with IBS compared to non-asthmatic patient with IBS. CONCLUSION Prevalence of IBS among asthma patients was significantly higher as compared to non-asthmatics. Routine screening of asthma patients and further studies to understand the pathogenesis underlying association between IBS and asthma should be conducted to detect and manage such patients effectively.
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Affiliation(s)
- Parkash Bachani
- Internal Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, PAK
| | - Love Kumar
- Internal Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, PAK
| | - Naresh Kumar
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | | | - Sidra Memon
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Sana Irfan
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Owais Alam
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Besham Kumar
- Internal Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK
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Özçağlayan Ö, Kurtoğlu Özçağlayan Tİ, Doğru M, Mete R. Vagus nerve assessment via ultrasonography in irritable bowel syndrome. Are there any changes of dimension in the vagus nerve? TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:503-507. [PMID: 32897223 DOI: 10.5152/tjg.2020.19353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIM Irritable bowel syndrome (IBS) is the functional gastrointestinal disorder which has closely relationship with Central Nervous System (CNS). VN is the major connector between CNS and Enteric Nervous System (ENS). The aim of this study was to investigate the possible changes of dimension of Vagus Nerve (VN) with Vagus ultrasonography (VU) in IBS. MATERIAL AND METHODS A total 119 patients which is consisted of 66 IBS patients appropriated with Rome IV criterias and 53 patients of control group were enrolled to the study. All patients were underwent to colonoscopy for role-out the organic pathologies, such as polyposis, inflammatory bowel syndromes, diverticulosis and colon cancer. Right Vagus (RV) and left Vagus (LV) nerve areas and diameters were calculated with VU. RESULTS There were no statistical difference of RV (p=0.445) and LV (p=0.944) diameter between two groups. There were also no statistical difference of RV (p=0.549) and LV (p=0.874) areas between IBS and control groups. CONCLUSION VU clearly depicted that there is no changes of dimension in VN areas and diameters in the IBS. This might show that VN is only a transporter of abnormal neuronal stimulations according to IBS pathophisiology.
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Affiliation(s)
- Ömer Özçağlayan
- Department of Radiology Tekirdağ Namık Kemal University, School of Medicine, Tekirdağ, Turkey
| | | | - Mücahit Doğru
- Department of Radiology Tekirdağ Namık Kemal University, School of Medicine, Tekirdağ, Turkey
| | - Rafet Mete
- Department of Gastroenterology, Tekirdağ Namık Kemal University, School of Medicine, Tekirdağ, Turkey
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Higher odds of irritable bowel syndrome among hospitalized patients using cannabis: a propensity-matched analysis. Eur J Gastroenterol Hepatol 2019; 31:756-765. [PMID: 30807448 DOI: 10.1097/meg.0000000000001382] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The endogenous cannabinoid system modulates many brain-gut and gut-brain physiologic pathways, which are postulated to be dysfunctional in irritable bowel syndrome (IBS). Herein, we examine the relationship between cannabis use disorder (CUD) and having IBS. PATIENTS AND METHODS After selecting patients aged 18 years and above from the 2014 Nationwide Inpatient Survey, we used the International Classification of Diseases, 9th ed. codes to identify individuals with CUD, IBS, and the established risk factors for IBS. We then estimated the crude and adjusted odds ratios of having a diagnosis of IBS with CUD and assessed for the interactions of CUD with other risk factors (SAS 9.4). We confirmed our findings in two ways: conducting a similar analysis on a previous Nationwide Inpatient Survey data (2012); and using a greedy algorithm to design a propensity-scored case-control (1 : 10) study, approximating a pseudorandomized clinical trial. RESULTS Out of 4 709 043 patients evaluated, 0.03% had a primary admission for IBS and 1.32% had CUD. CUD was associated with increased odds of IBS [adjusted odds ratio: 2.03; 95% confidence interval (CI): 1.53-2.71]. CUD was related to higher odds for IBS among males compared with females (3.48; 1.98-6.12 vs. 1.48; 0.88-2.50), and Hispanics and Caucasians compared with Blacks (5.28; 1.77-15.76, 1.80; 1.02-3.18 vs. 1.80; 0.65-5.03). On propensity-matching, CUD was associated with 80% increased odds for IBS (1.82; 1.27-2.60). CONCLUSION Our findings suggest that CUD is significantly associated with IBS among the general population. Males, Caucasians, and Hispanics might be more impacted by CUD associated IBS. Additional biomedical studies are required to elucidate this relationship.
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Zubcevic J, Richards EM, Yang T, Kim S, Sumners C, Pepine CJ, Raizada MK. Impaired Autonomic Nervous System-Microbiome Circuit in Hypertension. Circ Res 2019; 125:104-116. [PMID: 31219753 PMCID: PMC6588177 DOI: 10.1161/circresaha.119.313965] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hypertension affects an estimated 103 million Americans, yet gaps in knowledge continue to limit its successful management. Rapidly emerging evidence is linking gut dysbiosis to many disorders and diseases including hypertension. The evolution of the -omics techniques has allowed determination of the abundance and potential function of gut bacterial species by next-generation bacterial sequencing, whereas metabolomics techniques report shifts in bacterial metabolites in the systemic circulation of hypertensive patients and rodent models of hypertension. The gut microbiome and host have evolved to exist in balance and cooperation, and there is extensive crosstalk between the 2 to maintain this balance, including during regulation of blood pressure. However, an understanding of the mechanisms of dysfunctional host-microbiome interactions in hypertension is still lacking. Here, we synthesize some of our recent data with published reports and present concepts and a rationale for our emerging hypothesis of a dysfunctional gut-brain axis in hypertension. Hopefully, this new information will improve the understanding of hypertension and help to address some of these knowledge gaps.
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Affiliation(s)
- Jasenka Zubcevic
- Department of Physiological Sciences, College of Veterinary Medicine; University of Florida, Gainesville FL32610
| | - Elaine M. Richards
- Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville FL32610
| | - Tao Yang
- Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville FL32610
| | - Seungbum Kim
- Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville FL32610
| | - Colin Sumners
- Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville FL32610
| | - Carl J Pepine
- Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville FL32610
| | - Mohan K Raizada
- Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville FL32610
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Davydov DM, Naliboff B, Shahabi L, Shapiro D. Asymmetries in reciprocal baroreflex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome. Neurogastroenterol Motil 2018; 30. [PMID: 28834014 DOI: 10.1111/nmo.13186] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 07/20/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Objective measures of pain severity remain ill defined, although its accurate measurement is critical. Reciprocal baroreflex mechanisms of blood pressure (BP) control were found to impact differently on pain regulation, and thus their asymmetry was hypothesized to also connect to chronic pain duration and severity. METHODS Seventy-eight female patients with irritable bowel syndrome (IBS) and 27 healthy women were assessed for IBS severity and chronicity, negative affect, and various measures of resting autonomic function including BP, heart rate and its variability (HRV), baroreceptor-sensitivity to activations and inhibitions, gains of brady- and tachy-cardiac baro-responses, gains of BP falls/rises, and BP start points for these spontaneous baroreflexes. KEY RESULTS IBS directly and indirectly (through increased negative affect) was associated with asymmetry between baroreceptor activations/inhibitions compared to symmetrical baroreflex reciprocity in the healthy women. In the IBS group, independently of specific IBS symptoms, pain chronicity was associated with (i) decreased BP falls coupled with either (a) decreased tachycardia associated with lower disease severity (earlier "pain resilience" mechanism), or (b) decreased bradycardia associated with higher disease severity (later "pain decompensation" mechanism), or (ii) increased BP start point for baroreceptor activations coupled with either (a) BP increase (delayed "pain adaptation" mechanism) or (b) affect-related HRV decrease (delayed "pain aggravation" mechanism). CONCLUSION AND INFERENCES We anticipate the findings to be a starting point for validating these autonomic metrics of pain suffering and pain coping mechanisms in other chronic pain syndromes to suggest them as biomarkers of its severity and duration for profiling and correct management of chronic pain patients.
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Affiliation(s)
- D M Davydov
- Laboratory of Neuroimmunopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia.,Department of Medical Development, GLMED Longevity & Beauty Residence, Moscow, Russia
| | - B Naliboff
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - L Shahabi
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - D Shapiro
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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Manabe N, Haruma K. Optimal acid suppressive treatment for adequate symptom relief and prevention of the complications of gastroesophageal reflux disease: differences in long-term clinical course and pathophysiology among disease subtypes. Esophagus 2017; 14:113-121. [DOI: 10.1007/s10388-016-0558-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
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Siddiqui S, Misra SP, Dwivedi M, Pant S. Irritable Bowel Syndrome and Bronchial Asthma: Are They Associated in Indian Population? J Clin Diagn Res 2017; 11:OC21-OC23. [PMID: 28384910 DOI: 10.7860/jcdr/2017/22530.9351] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Accepted: 10/10/2016] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Irritable Bowel Syndrome (IBS), a common gastrointestinal (GI) disorder has been linked with asthma implying a clue to its pathophysiology as being some form of allergic response. Previous studies from other parts of the world have shown both the presence as well as an absence of an association between them. AIM We conducted a cross-sectional study to find an association between IBS and asthma, in an Indian cohort. MATERIALS AND METHODS Seventy patients of IBS diagnosed by exclusion and ROME III criteria with a matched control group were questioned for GI, respiratory symptoms along with their spirometry analysis. Those having reversible bronchoconstriction were categorized as asthmatic. RESULTS The prevalence of asthma in the IBS group of 16 females and 54 males was 12 (17.14%) as compared to 14 (20%) in control group. Chi-square test revealed the Odds Ratio (OR) for prevalence of asthma in IBS as 0.828 with 95% Confidence Interval (CI) between 0.320 and 2.121 (p=0.664) which was non-significant (p>0.05). CONCLUSION This study denies the presence of association between IBS and asthma among Indian cohorts and suggests that regional variations are present in the above association.
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Affiliation(s)
- Salahuddin Siddiqui
- Resident, Department of Internal Medicine, Allegheny Health Network Medical Education Consortium , Pittsburgh, Pennsylvania, USA
| | - Sri Prakash Misra
- Professor, Department of Gastroenterology and Hepatology, MLN Medical College , Allahabad, Uttar Pradesh, India
| | - Manisha Dwivedi
- Professor, Department of Gastroenterology and Hepatology, MLN Medical College , Allahabad, Uttar Pradesh, India
| | - Sanjay Pant
- Senior Resident, Department of Gastroenterology and Hepatology, MLN Medical College , Allahabad, Uttar Pradesh, India
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Davydov DM, Naliboff B, Shahabi L, Shapiro D. Baroreflex mechanisms in Irritable Bowel Syndrome: Part I. Traditional indices. Physiol Behav 2016; 157:102-8. [PMID: 26836276 DOI: 10.1016/j.physbeh.2016.01.042] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 01/28/2016] [Accepted: 01/29/2016] [Indexed: 12/13/2022]
Abstract
OBJECTIVE This study was conducted to present evidence of differences in autonomic regulation of cardiovascular activity and its role in the severity of specific (disease-related) and non-specific (negative affect and chronic pain-related) symptoms in individuals with Irritable Bowel Syndrome (IBS). METHODS Seventy-eight female patients with IBS and 27 healthy women age 18-62 years were assessed for IBS symptoms, negative affect, and baroreceptor sensitivity (BRS), blood pressure (BP), heart rate, and heart rate variability (HRV) at rest. Direct and indirect regression effects were examined with application of the bootstrap procedure to validate findings. RESULTS IBS was reliably related to lower resting BRS, higher BP, and higher negative affect compared to healthy controls. Longer disease duration (chronicity) was related to BRS decrease coupled with systolic BP increase (95% CIs=-0.14 to -0.01). Three autonomic mechanisms associated with BRS decrease were found to further regulate severity of IBS symptoms. Lower BRS was related to higher IBS severity in general if the effect was transferred through the decrease of low frequency power of HRV (e.g., 95% CIs=-0.039 to -0.001 for abdominal pain severity). However, lower BRS was related to lower IBS severity in general if the effect was transferred through diastolic BP increase (95% CIs=0.01-0.11 for abdominal pain severity). Lower BRS was related to higher abdominal pain severity coupled with high negative affect if the effect was transferred through the decrease of higher frequency power of HRV (95% CIs=-0.026 to -0.003). CONCLUSIONS These findings indicate that different cardiovascular mechanisms are associated with IBS development and the increase and decrease of severity of IBS symptoms. Their assessment suggests ways to personalize treatment of IBS.
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Affiliation(s)
- Dmitry M Davydov
- Laboratory of Neuroimmunopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 8 Baltiyskaia ul., Moscow 125315, Russia.
| | - Bruce Naliboff
- Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, 760 Westwood Plaza, Los Angeles, CA 90095, United States.
| | - Leila Shahabi
- Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
| | - David Shapiro
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, 760 Westwood Plaza, Los Angeles, CA 90095, United States.
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Camilleri M. Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms. J Physiol 2014; 592:2967-80. [PMID: 24665101 DOI: 10.1113/jphysiol.2014.270892] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The gastrointestinal tract is a vast neuroendocrine organ with extensive extrinsic and intrinsic neural circuits that interact to control its function. Circulating and paracrine hormones (amine and peptide) provide further control of secretory, absorptive, barrier, motor and sensory mechanisms that are essential to the digestion and assimilation of nutrients, and the transport and excretion of waste products. Specialized elements of the mucosa (including enteroendocrine cells, enterocytes and immune cells) and the microbiome interact with other intraluminal contents derived from the diet, and with endogenous chemicals that alter the gut's functions. The totality of these control mechanisms is often summarized as the brain-gut axis. In irritable bowel syndrome (IBS), which is the most common gastrointestinal disorder, there may be disturbances at one or more of these diverse control mechanisms. Patients present with abdominal pain in association with altered bowel function. This review documents advances in understanding the pathophysiological mechanisms in the brain-gut axis in patients with IBS. It is anticipated that identification of one or more disordered functions in clinical practice will usher in a renaissance in the management of IBS, leading to effective therapy tailored to the needs of the individual patient.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
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Liu Q, Wang EM, Yan XJ, Chen SL. Autonomic functioning in irritable bowel syndrome measured by heart rate variability: a meta-analysis. J Dig Dis 2013; 14:638-46. [PMID: 23927739 DOI: 10.1111/1751-2980.12092] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To analyze autonomic functioning which presented as the high frequency (HF) component of heart rate variability, a measurement of vagal tone, and the ratio of low frequency (LF) to HF (LF : HF), an indicator of sympathovagal balance in irritable bowel syndrome (IBS) patients. METHODS We identified relevant studies by performing a literature search of MEDLINE, EMBASE and the ISI Web of Knowledge to 31 March 2013. Pooled effect sizes with 95% confidence interval (CI) were calculated using a random effects model. Between-study heterogeneity was assessed using the Q test and I(2) statistic. RESULTS In all, 11 articles including 392 IBS patients and 263 controls met the inclusion criteria of the analysis. IBS patients had lower HF band power (Hedges's g = -0.38, 95% CI -0.68 to -0.09) than the controls (I(2) = 63.6%, P = 0.003). Moreover, IBS patients showed a higher LF : HF (Hedges's g = 0.43, 95% CI 0.13-0.74), with no significant heterogeneity. A subgroup analysis of the HF index according to the recording time yielded different results for the IBS patients and controls. Additionally, constipation-predominant IBS (IBS-C) patients had decreased HF band power, whereas no significant difference was found in LF : HF. CONCLUSIONS Impaired parasympathetic functioning and abnormal sympathovagal balance may be involved in the pathogenesis of IBS. Vagal dysfunction is more obvious in the IBS-C subgroup.
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Affiliation(s)
- Qing Liu
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, Shanghai, China
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Thomaidis T, Goetz M, Gregor SP, Hoffman A, Kouroumalis E, Moehler M, Galle PR, Schwarting A, Kiesslich R. Irritable bowel syndrome and organic diseases: A comparative analysis of esophageal motility. World J Gastroenterol 2013; 19:6408-6415. [PMID: 24151359 PMCID: PMC3801311 DOI: 10.3748/wjg.v19.i38.6408] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Revised: 01/24/2013] [Accepted: 05/10/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the esophageal motility in patients with irritable bowel syndrome (IBS) and to compare those with patients with autoimmune disorders.
METHODS: 15 patients with IBS, 22 with systemic lupus erythematosus (SLE) and 19 with systemic sclerosis (SSc) were prospectively selected from a total of 115 patients at a single university centre and esophageal motility was analysed using standard manometry (Mui Scientific PIP-4-8SS). All patients underwent esophago-gastro-duodenoscopy before entering the study so that only patients with normal endoscopic findings were included in the current study. All patients underwent a complete physical, blood biochemistry and urinary examination. The grade of dysphagia was determined for each patient in accordance to the intensity and frequency of the presented esophageal symptoms. Furthermore, disease activity scores (SLEDAI and modified Rodnan score) were obtained for patients with autoimmune diseases. Outcome parameter: A correlation coefficient was calculated between amplitudes, velocity and duration of the peristaltic waves throughout esophagus and patients’ dysphagia for all three groups.
RESULTS: There was no statistical difference in the standard blood biochemistry and urinary analysis in all three groups. Patients with IBS showed similar pathologic dysphagia scores compared to patients with SLE and SSc. The mean value of dysphagia score was in IBS group 7.3, in SLE group 6.73 and in SSc group 7.56 with a P-value > 0.05. However, the manometric patterns were different. IBS patients showed during esophageal manometry peristaltic amplitudes at the proximal part of esophagus greater than 60 mmHg in 46% of the patients, which was significant higher in comparison to the SLE (11.8%) and SSc-Group (0%, P = 0.003). Furthermore, IBS patients showed lower mean resting pressure of the distal esophagus sphincter (Lower esophageal sphincter, 22 mmHg) when compared with SLE (28 mmHg, P = 0.037) and SSc (26 mmHg, P = 0.052). 23.5% of patients with SLE showed amplitudes greater as 160 mmHg in the distal esophagus (IBS and SSc: 0%) whereas 29.4% amplitudes greater as 100 mmHg in the middle one (IBS: 16.7%, SSc: 5.9% respectively, P = 0.006). Patients with SSc demonstrated, as expected, in almost half of the cases reduced peristalsis or even aperistalsis in the lower two thirds of the esophagus. SSc patients demonstrated a negative correlation coefficient between dysphagia score, amplitude and velocity of peristaltic activity at middle and lower esophagus [r = -0.6, P < 0.05].
CONCLUSION: IBS patients have comparable dysphagia-scores as patients with autoimmune disorders. The different manometric patterns might allow differentiating esophageal symptoms based on IBS from other organic diseases.
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MESH Headings
- Adult
- Autoimmunity
- Deglutition
- Deglutition Disorders/diagnosis
- Deglutition Disorders/etiology
- Deglutition Disorders/physiopathology
- Endoscopy, Digestive System
- Esophageal Sphincter, Lower/physiopathology
- Esophagus/physiopathology
- Female
- Germany
- Humans
- Irritable Bowel Syndrome/complications
- Irritable Bowel Syndrome/diagnosis
- Irritable Bowel Syndrome/physiopathology
- Lupus Erythematosus, Systemic/complications
- Lupus Erythematosus, Systemic/diagnosis
- Lupus Erythematosus, Systemic/immunology
- Lupus Erythematosus, Systemic/physiopathology
- Male
- Manometry
- Middle Aged
- Peristalsis
- Prospective Studies
- Scleroderma, Systemic/complications
- Scleroderma, Systemic/diagnosis
- Scleroderma, Systemic/immunology
- Scleroderma, Systemic/physiopathology
- Severity of Illness Index
- Surveys and Questionnaires
- Time Factors
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14
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Han B. Correlation between gastrointestinal hormones and anxiety-depressive states in irritable bowel syndrome. Exp Ther Med 2013; 6:715-720. [PMID: 24137253 PMCID: PMC3786850 DOI: 10.3892/etm.2013.1211] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Accepted: 06/03/2013] [Indexed: 12/11/2022] Open
Abstract
The aim of this study was to investigate the mechanism(s) of action of gastrointestinal hormones in the pathogenesis of irritable bowel syndrome (IBS), and the correlation between gastrointestinal hormones and psychological factors. Patients with IBS were divided into IBS with normal emotional state ratings and IBS in anxiety-depressive states groups. The two groups were then subdivided into IBS-constipation predominant (IBS-C) and IBS-diarrhea predominant (IBS-D) groups. Non-IBS patients with normal depression and anxiety ratings were recruited as controls. The serum concentrations of somatostatin (SS) and vasoactive intestinal peptide (VIP) were measured by radioimmunoassay, and the expression of SS and VIP in the colonic mucosa was detected by immunohistochemistry and radioimmunoassay. The anxiety-depression scores of patients with IBS were significantly different from those of the control group (P<0.05). The expression levels of SS and VIP in the serum and colonic mucosa of the patients with IBS were higher compared with those of the control group. Furthermore, the expression level of SS in the IBS-C group demonstrated a significantly larger increase than that in the IBS-D group (P<0.05); however, there was no significant difference in the expression of VIP between the IBS-C and IBS-D groups (P>0.05). In addition, the expression levels of SS and VIP in the IBS groups with normal emotional state ratings were notably different from those in the IBS groups in anxiety-depressive states (P<0.05). Anxiety-depressive states may lead to changes in the secretion of SS and VIP, and subsequently to changes in gastrointestinal motility and function.
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Affiliation(s)
- Baojuan Han
- Department of Gastroenterology, Xingtai People's Hospital, Xingtai, Hebei 054031, P.R. China
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15
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Gao J. Correlation between anxiety-depression status and cytokines in diarrhea-predominant irritable bowel syndrome. Exp Ther Med 2013; 6:93-96. [PMID: 23935726 PMCID: PMC3735566 DOI: 10.3892/etm.2013.1101] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2013] [Accepted: 04/17/2013] [Indexed: 12/12/2022] Open
Abstract
The aim of this study was to investigate the correlation between anxiety-depression status and cytokines in diarrhea-predominant irritable bowel syndrome (IBS-D). IBS-D patients were divided into an anxiety-depression IBS-D group and a non-anxiety-depression IBS-D group. Patients without IBS, anxiety or depression were selected as the control group. Scoring was performed using the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Levels of IL-1β and IL-10 in the blood and sigmoid colon mucosa were detected, and the proportions of IL-1β- and IL-10-positive cells in the sigmoid colon mucosa were determined. The results demonstrated that the SDS and SAS scores in the IBS-D group were significantly higher than those in the control group (P<0.05). The levels of IL-1β in the blood and sigmoid colon mucosa and the proportion of IL-1β-positive cells in the sigmoid colon mucosa in the IBS-D group were significantly higher than those in the control group (P<0.05). The levels of IL-10 in the blood and sigmoid colon mucosa and the proportion of IL-10-positive cells in the IBS-D group were significantly lower than those in the control group (P<0.05). The levels of IL-1β in the blood and sigmoid colon mucosa and the proportion of IL-1β-positive cells in the anxiety-depression IBS-D group were significantly higher than those in the non-anxiety-depression IBS-D group, and the levels of IL-10 and the proportion of IL-10-positive cells in the anxiety-depression IBS-D group were significantly lower than those in the non-anxiety-depression IBS-D group (P<0.05). Anxiety-depression status may cause the IL-1β and IL-10 levels in IBS patients to change and result in an imbalance of the proinflammatory and anti-inflammatory cytokines, leading to the occurrence or aggravation of IBS.
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Affiliation(s)
- Jingguo Gao
- Department of Digestive System, Xingtai People's Hospital, Xingtai, Hebei 054031, P.R. China
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16
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Zhang X, Cao B, Yan N, Liu J, Wang J, Tung VOV, Li Y. RETRACTED: Vagus nerve stimulation modulates visceral pain-related affective memory. Behav Brain Res 2013; 236:8-15. [DOI: 10.1016/j.bbr.2012.08.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Revised: 07/11/2012] [Accepted: 08/16/2012] [Indexed: 12/28/2022]
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17
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Mazur M, Furgała A, Jabłoński K, Mach T, Thor P. Autonomic nervous system activity in constipation-predominant irritable bowel syndrome patients. Med Sci Monit 2012; 18:CR493-CR499. [PMID: 22847198 PMCID: PMC3560712 DOI: 10.12659/msm.883269] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Accepted: 01/19/2012] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The main mechanism underlying irritable bowel syndrome is currently believed to be a dysfunction of the brain-gut axis. Autonomic nervous system dysfunction can contribute to development of irritable bowel syndrome symptoms by disturbing visceral sensations. MATERIAL/METHODS Thirty patients with a diagnosis of constipation-predominant irritable bowel syndrome and 30 healthy volunteers were included in the study. Resting and functional autonomic nervous system tests and percutaneous electrogastrography were performed. Plasma adrenalin, noradrenalin, insulin, ghrelin and cholecystokinin activity was analyzed. RESULTS Increased sympathetic activation with disturbed parasympathetic function was demonstrated. Patients had substantially higher plasma catecholamine concentration, which confirms sympathetic overbalance. Hyperinsulinemia may explain sympathetic predominance followed by gastric and intestinal motility deceleration. Abnormal, reduced ghrelin and cholecystokinin titre may disturb brain-gut axis functioning and may be responsible for gastric motility deceleration. In electrogastrography, distinctly lower values of fasting normogastria percentage and dominant power were observed. Patients had substantially lower slow wave coupling percentage both in fasting and postprandial periods, which negatively correlated with plasma catecholamines level. Gastric myoelectrical activity disturbances may result from lack of sympatho-parasympathetic equilibrium. CONCLUSIONS Central sympathetic influence within the brain-gut axis is most probably responsible for myoelectrical activity disturbances in irritable bowel syndrome patients.
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Affiliation(s)
- Marcel Mazur
- Department of Pathophysiology, Jagiellonian University, Medical College, Cracow, Poland
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18
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Mazurak N, Seredyuk N, Sauer H, Teufel M, Enck P. Heart rate variability in the irritable bowel syndrome: a review of the literature. Neurogastroenterol Motil 2012; 24:206-16. [PMID: 22256893 DOI: 10.1111/j.1365-2982.2011.01866.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with irritable bowel syndrome (IBS) often present with disturbances of bowel habits (diarrhea, constipation) and abdominal pain/discomfort that are modulated by the autonomic nerve system (ANS). In this narrative review, we analyzed studies that measured ANS functioning in IBS by means of heart rate variability (HRV). METHODS The PUBMED was searched with the keywords 'irritable bowel syndrome' AND ('heart rate variability' OR 'autonomic function'). We included only papers that used 'traditional' HRV indices and diagnosed IBS based on Manning or Rome criteria. Studies were sub-grouped according to methodological features of HRV analysis (24-h monitoring, short-term laboratory records, records during sleep). KEY RESULTS Most studies reported no difference in HRV when the IBS population was compared to healthy controls. Dividing the IBS sample into subgroups--according to their predominant bowel symptoms, the severity of clinical course, the presence of depressive symptoms, or a history of abuse in the past--revealed changes in autonomic functioning. CONCLUSIONS & INFERENCES Patients with IBS appear to experience symptoms that may be the result of changes in ANS functioning. HRV measures in clinical routine may allow assessing these changes, but further studies performed in a standardized fashion should improve the validity of HRV measures for clinical research first.
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Affiliation(s)
- N Mazurak
- Department of Psychosomatic Medicine and Psychotherapy, University Hospital, Tübingen, Germany
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19
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Panicker R, Arifhodzic N, Al Ahmad M, Ali SA. Association and symptom characteristics of irritable bowel syndrome among bronchial asthma patients in Kuwait. Ann Thorac Med 2011; 5:37-42. [PMID: 20351959 PMCID: PMC2841807 DOI: 10.4103/1817-1737.58958] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2009] [Accepted: 12/02/2009] [Indexed: 12/11/2022] Open
Abstract
CONTEXT: Excess prevalence of irritable bowel syndrome in asthma has been reported, suggesting a link between these two conditions. AIMS: To investigate the association between irritable bowel syndrome (IBS) and asthma, and explore the symptoms of IBS among asthma patients in Kuwait. SETTINGS AND DESIGN: Case control study. METHODS: In a tertiary center, for allergy and asthma, 138 patients aged 20-65 years, with asthma, diagnosed clinically and by spirometry, were compared with 145 healthy, non-asthmatic controls matched for age, gender and nationality. Cases and controls completed a self-administered questionnaire of irritable bowel syndrome diagnosis (ROME II criteria). STATISTICAL ANALYSIS USED: The data were analyzed using SPSS software, and proportions were tested with Chi-square or Fisher's test. Odds ratio (OR) with 95% Confidence Interval (CI) were calculated to identify the associated risk factors. The demographic variables were selected for logistic regression analysis. RESULTS: A significantly large proportion (39.13%) of asthmatics had IBS as compared to 7.93% controls (P < 0.001). A higher proportion of females with IBS were observed in cases and controls (74%, 61.54%). IBS was seen in 87% cases using inhalers, and in 13% with additional oral theophylline (P < 0.001). As many as 66.6% cases, had IBS with relatively short duration of asthma (1-5 years, P < 000). Predominant symptoms of IBS in asthmatics were abdominal discomfort or distension (64.8% vs. 11.5%), (P < 0.000, OR = 14.1; 95%CI: 3.748-53.209), bloated feeling of abdomen (74.1% vs. 34.62% (P < 0.001, OR = 5.38; 95%CI:1.96-14.84)), increased frequency of stools (63%, P < 0.006). CONCLUSIONS: Irritable bowel syndrome in asthmatics was significantly high, more in the female asthmatics. Abdominal discomfort, persistent bloated feeling, increased frequency of passing stools were the most common IBS symptoms observed.
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20
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Sowder E, Gevirtz R, Shapiro W, Ebert C. Restoration of vagal tone: a possible mechanism for functional abdominal pain. Appl Psychophysiol Biofeedback 2010; 35:199-206. [PMID: 20229150 DOI: 10.1007/s10484-010-9128-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Functional abdominal pain (FAP) causes disruption of daily activities/missed school days, over utilization of healthcare, unnecessary surgeries, and anxiety in 10-15% of children. Its etiology is not clearly understood, however the success of several clinical protocols suggests that autonomic dysregulation is a factor. In this study autonomic activity, including heart rate variability (HRV), was compared between children with FAP and a comparison group. Twenty children with FAP and 10 children without FAP between the ages of 5 and 17 years old were compared on autonomic regulation using an ambulatory system at baseline and 8 weeks later. Children with FAP participated in 6 sessions of HRV biofeedback aimed at normalizing autonomic balance. At baseline, children with FAP appear to have more autonomic dysregulation than children without FAP. After completing HRV biofeedback, the FAP group was able to significantly reduce their symptoms in relation to significantly increasing their autonomic balance. In a sample of children with FAP, it appears that HRV biofeedback treatment improved their symptoms and that a change in vagal tone was a potential mediator for this improvement. The present study appears to point to excessive vagal withdrawal as an underlying mechanism of FAP.
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Affiliation(s)
- Erik Sowder
- CSPP@Alliant International University, 10455 Pomerado Rd, San Diego, CA 92131, USA
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21
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Wong F, Rodrigues AC, King CD, Riley JL, Schmidt S, Vierck CJ, Mauderli AP. Relationships between Irritable Bowel Syndrome Pain, Skin Temperature Indices of Autonomic Dysregulation, and Sensitivity to Thermal Cutaneous Stimulation. PAIN RESEARCH AND TREATMENT 2010; 2010:949027. [PMID: 22110918 PMCID: PMC3196965 DOI: 10.1155/2010/949027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2010] [Accepted: 06/03/2010] [Indexed: 01/18/2023]
Abstract
This study evaluated relationships between irritable bowel syndrome (IBS) pain, sympathetic dysregulation, and thermal pain sensitivity. Eight female patients with diarrhea-predominant IBS and ten healthy female controls were tested for sensitivity to thermal stimulation of the left palm. A new method of response-dependent thermal stimulation was used to maintain pain intensity at a predetermined level (35%) by adjusting thermal stimulus intensity as a function of pain ratings. Clinical pain levels were assessed prior to each testing session. Skin temperatures were recorded before and after pain sensitivity testing. The temperature of palmar skin dropped (1.5°C) when the corresponding location on the opposite hand of control subjects was subjected to prolonged thermal stimulation, but this response was absent for IBS pain patients. The patients also required significantly lower stimulus temperatures than controls to maintain a 35% pain rating. Baseline skin temperatures of patients were significantly correlated with thermode temperatures required to maintain 35% pain ratings. IBS pain intensity was not significantly correlated with skin temperature or pain sensitivity. The method of response-dependent stimulation revealed thermal hyperalgesia and increased sympathetic tone for chronic pain patients, relative to controls. Similarly, a significant correlation between resting skin temperatures and thermal pain sensitivity for IBS but not control subjects indicates that tonic sympathetic activation and a thermal hyperalgesia were generated by the chronic presence of visceral pain. However, lack of a significant relationship between sympathetic tone and ratings of IBS pain casts doubt on propositions that the magnitude of IBS pain is determined by psychological stress.
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Affiliation(s)
- Fong Wong
- Department of Prosthodontics, College of Dentistry, University of Florida, 1600 SW Archer Rd, D11-006 Gainesville, FL 32610, USA
| | | | - Christopher D. King
- Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, 1600 SW Archer Rd, D11-006 Gainesville, FL 32610, USA
| | - Joseph L. Riley
- Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, 1600 SW Archer Rd, D11-006 Gainesville, FL 32610, USA
| | - Siegfried Schmidt
- Community Health & Family Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Charles J. Vierck
- Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Andre P. Mauderli
- Department of Prosthodontics, College of Dentistry, University of Florida, 1600 SW Archer Rd, D11-006 Gainesville, FL 32610, USA
- Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA
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22
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Sjölund K, Ekman R, Wierup N. Covariation of plasma ghrelin and motilin in irritable bowel syndrome. Peptides 2010; 31:1109-12. [PMID: 20338210 DOI: 10.1016/j.peptides.2010.03.021] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2009] [Revised: 03/16/2010] [Accepted: 03/17/2010] [Indexed: 12/26/2022]
Abstract
We have previously shown that ghrelin is mainly localized to the stomach but also occurs, together with the prokinetic hormone motilin, in endocrine cells in the proximal small intestine. This study explored ghrelin and motilin concentrations in plasma in relation to gastrointestinal motility and whether plasma ghrelin is changed in patients with irritable bowel syndrome (IBS). Nine patients with severe IBS and 10 healthy subjects underwent stationary antro-duodeni-jejunal manometry; blood was sampled during similar motility phases in the two groups. The motility phases were monitored and blood samples were collected during fasting and after food intake. Plasma was analyzed for two forms of ghrelin (octanylated and desoctanylated) as well as for motilin. In IBS patients circulating motilin levels covaried with total ghrelin levels (r=0.90; p<0.004), octanylated ghrelin (r=0.77; p<0.02) and desoctanylated ghrelin (r=0.69; p<0.04). No such correlations were seen in the control group. Octanylated ghrelin comprised 35.3+/-3.9% (mean+/-SEM) of the total circulating ghrelin in the IBS patients compared to 40.4+/-4.5% (mean+/-SEM) in the control group (NS). Ghrelin covaried with motilin in plasma in IBS but not in plasma from healthy subjects. This suggests the two peptides act together in IBS.
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Affiliation(s)
- Kristina Sjölund
- Department of Internal Medicine, Trelleborg Hospital, Hedvägen 46, S-231 85 Trelleborg, Sweden.
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23
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Farmer AD, Aziz Q, Tack J, Van Oudenhove L. The future of neuroscientific research in functional gastrointestinal disorders: integration towards multidimensional (visceral) pain endophenotypes? J Psychosom Res 2010; 68:475-81. [PMID: 20403507 DOI: 10.1016/j.jpsychores.2009.12.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2009] [Revised: 12/15/2009] [Accepted: 12/21/2009] [Indexed: 12/19/2022]
Abstract
The growing evidence for a key role of psychophysiological processes in the etiopathogenesis of functional gastrointestinal disorders (FGID) originates from various sources, including epidemiological, psychometric, physiological, and behavioural studies. Functional neuroimaging has improved our knowledge about central processing of visceral pain, a defining feature of FGID. However, results have been disappointingly inconsistent, often due to psychosocial factors not being controlled for. In this paper, we aim to show that using integrated research strategies, encompassing a number of scientific disciplines, is critical to advancing our understanding of FGID. We will illustrate this by describing recent integrative studies that may serve as good examples. More specifically, future FGID neuroimaging studies should control for psychosocial factors and incorporate methods from other branches of neuroscience outside this field, especially cognitive, affective and autonomic neuroscience. We therefore propose a framework for the development of an integrative cross-disciplinary research strategy based on advancing our understanding of visceral nociceptive physiology in health as well as vulnerability and susceptibility factors for FGID. This approach will allow the identification of factors responsible for the inter-individual differences in visceral pain perception and susceptibility to chronic visceral pain, leading to the description of multidimensional (visceral) pain "endophenotypes." These may represent the critical steps needed towards a pathophysiological, rather than symptom-based, classification of FGID, which may be more suitable for genetic association studies. This approach may ultimately culminate in individual tailoring of treatment, in addition to disease prevention, thereby improving outcomes for the patient and researcher alike.
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Affiliation(s)
- Adam D Farmer
- Neurogastroenterology Group, Wingate Institute of Neurogastroenterology, Centre for Gastroenterology, Blizzard Centre for Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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24
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Chen S, Li J, Zhang L, Dong X, Gao W, Mo J, Chen H, Xiao S, Li Y. 5-HT 3 receptors mediate the time-dependent vagal afferent modulation of nociception during chronic food allergen-sensitized visceral hyperalgesia in rats. Neurogastroenterol Motil 2009; 21:1222-e113. [PMID: 19558425 DOI: 10.1111/j.1365-2982.2009.01335.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Converging lines of evidence demonstrate a vagally mediated antinociceptive pathway in animals undergoing acute visceral insults, the contribution of this system to visceral pain following chronic noxious stimuli is unknown. 5-HT(3) receptor (5-HT(3)Rs) on spinal afferents are crucially involved in nociceptive processing, the role of 5-HT(3)Rs on vagal afferents is unclear. The aim of the present study was to determine the contribution of vagal afferents to visceral nociception in rats undergoing chronic luminal allergen stimulation and whether it involves vagal 5-HT(3)Rs. Sensitized rats received chicken egg albumin (EA, 1 mg mL(-1)) in drinking water for 2 weeks (day 1-14). Visceromotor response (VMR) to colorectal distension [colorectal distension (CRD), 60 mmHg] and the levels of mRNA encoding 5-HT(3)R (including 3A and 3B subunits) in the nodose ganglia (NG) were evaluated on day 2, 4, 8 and 15. Chronic EA challenge induced gradually increased visceral nociception, with a peak on day 15. Subdiaphragmatic vagotomy or functional deafferentation with capsaicin abolished this time-dependent manner, inducing hyperalgesia from day 2, lasting to day 15. Intraluminal infusion of a 5-HT(3)R antagonist (granisetron), whether alone or infused after local mucosa anaesthetic with 1% lidocaine, mimicked the effects of vagotomy. The mRNA levels for 5-HT(3B) or 5-HT(3A) subunit in the NG showed an opposite time-course to that of visceral pain, which increased from day 2, then decreased gradually to levels lower than those of controls. Our results demonstrate a time-dependent vagal afferent modulation of chronic allergen-sensitized visceral hyperalgesia, which may involve a 5-HT(3)R pathway.
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Affiliation(s)
- S Chen
- Department of Gastroenterology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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25
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Spetalen S, Sandvik L, Blomhoff S, Jacobsen MB. Autonomic function at rest and in response to emotional and rectal stimuli in women with irritable bowel syndrome. Dig Dis Sci 2008; 53:1652-9. [PMID: 17990112 DOI: 10.1007/s10620-007-0066-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2007] [Accepted: 10/14/2007] [Indexed: 12/17/2022]
Abstract
Our aim was to study autonomic function in patients with Irritable bowel syndrome (IBS) without constipation and psychiatric comorbidity. Respiratory sinus arrhythmia (RSA) (representing cardiac vagal activity), skin conductance (representing sympathetic activity) and heart rate were measured at baseline and as a response to emotional stress and rectal discomfort in 33 women with IBS and 21 healthy women. Baseline heart rate was higher in the patients than in the healthy volunteers. Both groups had decreased RSA and increased heart rate and skin conductance level when exposed to emotional stress, but the autonomic responses did not differ significantly between the groups. At discomfort threshold the patients had increased heart rate response and skin conductance amplitude when compared to the healthy volunteers. Correlations between autonomic responses and the depression subscale of the Hospital Anxiety and Depression (HAD) score differed markedly between the diarrhea-predominant IBS patients and the IBS patients with alternating stool habits.
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Affiliation(s)
- Signe Spetalen
- Department of Medicine, Rikshospitalet University Hospital, Oslo, Norway.
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26
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Chen SL, Wu XY, Cao ZJ, Fan J, Wang M, Owyang C, Li Y. Subdiaphragmatic vagal afferent nerves modulate visceral pain. Am J Physiol Gastrointest Liver Physiol 2008; 294:G1441-9. [PMID: 18420825 PMCID: PMC3222235 DOI: 10.1152/ajpgi.00588.2007] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Activation of the vagal afferents by noxious gastrointestinal stimuli suggests that vagal afferents may play a complex role in visceral pain processes. The contribution of the vagus nerve to visceral pain remains unresolved. Previous studies reported that patients following chronic vagotomy have lower pain thresholds. The patient with irritable bowel syndrome has been shown alteration of vagal function. We hypothesize that vagal afferent nerves modulate visceral pain. Visceromotor responses (VMR) to graded colorectal distension (CRD) were recorded from the abdominal muscles in conscious rats. Chronic subdiaphragmatic vagus nerve sections induced 470, 106, 51, and 54% increases in VMR to CRD at 20, 40, 60 and 80 mmHg, respectively. Similarly, at light level of anesthesia, topical application of lidocaine to the subdiaphragmatic vagus nerve in rats increased VMR to CRD. Vagal afferent neuronal responses to low or high-intensity electrical vagal stimulation (EVS) of vagal afferent Adelta or C fibers were distinguished by calculating their conduction velocity. Low-intensity EVS of Adelta fibers (40 microA, 20 Hz, 0.5 ms for 30 s) reduced VMR to CRD at 40, 60, and 80 mmHg by 41, 52, and 58%, respectively. In contrast, high-intensity EVS of C fibers (400 microA, 1 Hz, 0.5 ms for 30 s) had no effect on VMR to CRD. In conclusion, we demonstrated that vagal afferent nerves modulate visceral pain. Low-intensity EVS that activates vagal afferent Adelta fibers reduced visceral pain. Thus EVS may potentially have a role in the treatment of chronic visceral pain.
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Affiliation(s)
- S L Chen
- Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0682, USA
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Ozol D, Uz E, Bozalan R, Türkay C, Yildirim Z. Relationship between asthma and irritable bowel syndrome: role of food allergy. J Asthma 2007; 43:773-5. [PMID: 17169830 DOI: 10.1080/02770900601031789] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The increasing prevalence of both asthma and irritable bowel syndrome (IBS) are major health problems. One hundred twenty-five patients with asthma and 95 healthy subjects were included in this study. The rate of IBS was 29.6% and 12.7% (p < 0.005), and the incidence of food allergy was 7.2% and 2.1% (p > 0.05) respectively for asthma and control group. There was no significant association between asthma related parameters, IBS, and food allergy. There is not a single clear reason as to what causes IBS, so further studies are needed to clarify the potential pathogenic mechanisms underlying the association between IBS and asthma.
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Affiliation(s)
- Duygu Ozol
- Faculty of Medicine, Department of Pulmonology, Fatih University, 40A/20 Cankaya, Ankara, Turkey.
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Abstract
Asian irritable bowel syndrome (IBS) studies not only confirm the truth of this functional disorder but also describe the current disease situation of this continent, with its variable socioeconomic backgrounds. Most Asian community IBS prevalence is within 5-10%, regardless of gender or ethnic character. As well as meeting the main Rome II criteria, Asian IBS subjects also have many minor symptoms. Thus this recommendation remains useful to diagnose Asian IBS. Also, female patients commonly express constipation-predominant (C-) symptoms. Extra-colonic symptoms are common in Asia, for example dyspepsia, insomnia and irritable urinary bladder. Asian IBS subjects do experience psychological disturbances including anxiety, depression, agoraphobia and neuroticism. Accordingly, their quality of life is poor and there is absenteeism leading to excessive physician visits. Abnormal gut motor and sensory functions have been indicated among the Asian IBS subjects. Now, there is evidence of altered colonic neuroimmune function leading to gut hypersensitivity and dysmotility. An Asia-Pacific trial also confirmed tegaserod efficacy on female C-IBS subjects. More than 90% of nurses have very limited IBS knowledge, and are unable even to explain it clearly. In conclusion, Western recommended criteria clearly diagnose Asian IBS and many factors are mutual leading to IBS. Current IBS treatments remain useful but additional reeducation for medical professionals appears to be needed.
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Affiliation(s)
- Full-Young Chang
- Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
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Abstract
The pathophysiology of IBS is complex and still incompletely known. Both central and peripheral factors, including psychosocial factors, abnormal GI motility and secretion, and visceral hypersensitivity, are thought to contribute to the symptoms of IBS. Several studies have demonstrated altered GI motor function in IBS patients and the pattern differs between IBS subgroups based on the predominant bowel pattern. Few studies have so far addressed GI secretion in IBS, but there are some evidence supporting altered secretion in the small intestine of IBS patients. Visceral hypersensitivity is currently considered to be perhaps the most important pathophysiological factor in IBS. Importantly, several external and internal factors can modulate visceral sensitivity, as well as GI motility, and enhanced responsiveness within the GI tract to for instance stress and nutrients has been demonstrated in IBS patients. Today IBS is viewed upon as a disorder of dysregulation of the so-called brain-gut axis, involving abnormal function in the enteric, autonomic and/or central nervous systems, with peripheral alterations probably dominating in some patients and disturbed central processing of signals from the periphery in others.
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Affiliation(s)
- Iris Posserud
- Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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van Orshoven NP, Andriesse GI, van Schelven LJ, Smout AJ, Akkermans LMA, Oey PL. Subtle involvement of the parasympathetic nervous system in patients with irritable bowel syndrome. Clin Auton Res 2006; 16:33-9. [PMID: 16477493 DOI: 10.1007/s10286-006-0307-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2004] [Accepted: 06/18/2005] [Indexed: 12/23/2022]
Abstract
This study comprises assessment of autonomic function in irritable bowel syndrome (IBS) patients, focusing on meal-related changes. In 18 IBS patients (4 males, mean age 45+/-3.0 [SEM] years) and 19 healthy volunteers (6 males, mean age 41+/-3.5 years) blood pressure, heart rate, heart rate variability and muscle sympathetic nerve activity (MSNA) were assessed before, during and after consumption of a standardized meal. In pre- and postprandial phase Valsalva maneuver, cold pressor test (CPT) and deep breathing test were carried out and Visual Analog Scale (VAS) scores for nausea, bloating and pain were obtained. In the IBS group, the meal induced significantly higher VAS scores for pain (P=0.002) and bloating (P=0.02). During food intake, the increase in blood pressure, heart rate and MSNA was equal in patients and controls, but the increase of LF/HF ratio of heart rate variability was significantly higher in the IBS group (median [quartiles] 2.29 [1.14-3.00] versus 0.77 [0.25-1.81]; P=0.03). IBS patients scored lower on pre- and postprandial RRmax/RRmin ratio during deep breathing (DB ratio, P=0.03). The increase in MSNA (burst frequency) in response to CPT tended to be higher in the IBS patients (P=0.07). We conclude that reactivity to food intake, measured as muscle sympathetic nerve activity, is normal in IBS patients. The lower DB ratio and higher LF/HF ratio during food intake in IBS patients is an indication of a reduced parasympathetic reactivity. These results suggest that reduced baseline activity as well as responsiveness of the parasympathetic system could play a role in the pathogenesis of IBS.
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Affiliation(s)
- Narender P van Orshoven
- Rudolf Magnus Institute of Neuroscience, Dept. of Clinical Neurophysiology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands
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Jun DW, Lee OY, Yoon HJ, Lee HL, Yoon BC, Choi HS, Lee MH, Lee DH, Kee CS. Bronchial hyperresponsiveness in irritable bowel syndrome. Dig Dis Sci 2005; 50:1688-91. [PMID: 16133970 DOI: 10.1007/s10620-005-2916-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2004] [Accepted: 01/05/2005] [Indexed: 12/18/2022]
Abstract
Extraintestinal symptoms are often found in patients with irritable bowel syndrome (IBS). Recent studies suggest that IBS is associated with bronchial hyperresponsiveness. But it is still arguable that the bronchial hyperresponsiveness is associated with IBS patients. The purpose of this study is to investigate the possible relationship between IBS and bronchial hyperresponsiveness. Forty-two patients with IBS and 42 control subjects were included in this study. All patients underwent pulmonary function, methacholine challenge, and skin prick tests. There was no statistical difference between the two groups with respect to percentage of all pulmonary function test parameters, including FEV(1)%, FCV%, FVC/FEV(1), and FEF(25 - 75)%. Only two persons in the alternating-type IBS patient group and one person in the control group tested positive in the methacholine provocation test. But all PC(20) values were above 16 mg/ml. These results do not demonstrate a relationship between bronchial hyperresponsiveness and IBS. However, a relationship might exist in a subpopulation of IBS patients.
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Affiliation(s)
- Dae Won Jun
- Divisions of Gastroenterology, Hanyang University School of Medicine, Seoul, South Korea
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Waring WS, Chui M, Japp A, Nicol EF, Ford MJ. Autonomic cardiovascular responses are impaired in women with irritable bowel syndrome. J Clin Gastroenterol 2004; 38:658-63. [PMID: 15319647 DOI: 10.1097/01.mcg.0000135362.35665.49] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS This study characterizes cardiovascular autonomic function in women with irritable bowel syndrome (IBS), using standardized techniques. BACKGROUND Autonomic dysfunction is believed to contribute to abnormal gastrointestinal motility and visceral hypersensitivity in IBS. There is mounting evidence of generalized impairment of autonomic activity in patients with IBS. STUDY Thirty women aged 39 years (95% C.I. 25-53 years) diagnosed with IBS, and 30 age-matched healthy women were studied. The ratio of low frequency to high frequency heart rate variability domains (LF:HF ratio) was used to represent cardiac sympathovagal activity, and orthostatic testing and sustained isometric handgrip exercise were used as sympathetic stimuli. Parasympathetic activity was represented by the expiratory to inspiratory R-R interval (E:I) ratio during deep breathing at 6 minutes. RESULTS LF:HF responses to handgrip exercise (316%, C.I. 134% to 498% vs. 107%, C.I. 15% to 153%; P < 0.05) and orthostatic testing (648%, C.I. 520% to 904% vs. 330%, C.I. 140% to 520%; P < 0.05) were higher in IBS patients than controls, and the E:I ratio was significantly lower (1.47, C.I. 1.33-1.61 vs. 1.20, C.I. 1.14-1.26; P < 0.01). CONCLUSIONS Autonomic cardiovascular function is impaired in IBS, manifest as attenuated cardio-vagal tone, and relative sympathetic excess during stimulated conditions.
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Affiliation(s)
- W Stephen Waring
- Clinical Pharmacology Unit and Research Centre, University of Edinburgh.
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Abstract
It is quite frequent to recognize celiac patients who show gastrointestinal motor abnormalities in clinical practice. In fact, in 30 to 60% of patients, physical examination and dyspeptic symptoms (epigastric discomfort, early satiety) suggest a gastrointestinal motility disorder. Consistent data are now available on the presence of a disturbed motility of the esophagus, stomach, small intestine, gallbladder, and colon of untreated celiac patients. Gastrointestinal abnormalities differ in different gastrointestinal districts. In fact, esophageal transit, gastric and gallbladder emptying, and orocecal transit time are delayed, while colonic transit is faster. These findings are related to the complex interactions among reduced absorption of food constituent (in particular, fat), neurologic alteration, and hormonal derangement. Motility disorders of the gut are also a predisposing factor in the development of small intestinal bacterial overgrowth and may contribute both to development of symptoms in some untreated celiacs and to the persistence of symptoms after gluten-free diet in some of them. All these alterations fortunately disappear after gluten-free diet, and patients return to well being status. Whatever the initial event in the pathogenesis of the celiac lesions may be, we know for certain at this time that gastrointestinal disturbances play an important role in the genesis of gastrointestinal symptoms in celiac disease and that surveillance for celiac disease in patients complaining of dysmotility-like dyspeptic symptoms should be increased.
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Affiliation(s)
- Antonio Tursi
- Digestive Endoscopy Unit, Lorenzo Bonomo Hospital, Andria (BA), Italy.
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Colecchia A, Sandri L, Staniscia T, Vestito A, Capodicasa S, Portincasa P, Mazzella G, Roda E, Festi D. Gallbladder motility and functional gastrointestinal disorders. Dig Liver Dis 2003; 35 Suppl 3:S30-S34. [PMID: 12974507 DOI: 10.1016/s1590-8658(03)00091-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Functional gastrointestinal disorders can be defined as 'a variable combination of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities'. Motor disorders are considered to be one of the pathogenetic mechanisms of these symptoms; in fact, it has been hypothesized that the smooth muscle of the whole gastrointestinal tract could be involved. Gallbladder motility has been evaluated in patients with dysmotility-like dyspepsia, irritable bowel syndrome and biliary disorders without gallstones; results of these observations are often inconclusive, conflicting and not always useful from a clinical point of view. The aim of this review is to explore the relationship between gallbladder motility and functional gastrointestinal disorders from pathogenetic and physiopathological points of view, and also to define the possible impact of these observations on clinical practice.
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Affiliation(s)
- A Colecchia
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy
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Roussos A, Koursarakos P, Patsopoulos D, Gerogianni I, Philippou N. Increased prevalence of irritable bowel syndrome in patients with bronchial asthma. Respir Med 2003; 97:75-9. [PMID: 12556015 DOI: 10.1053/rmed.2001.1409] [Citation(s) in RCA: 90] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract. IBS may represent a primary disorder of gastrointestinal motility accompanied with motor dysfunction in various extraintestinal sites. Recent studies suggest that IBS is associated with bronchial hyper-responsiveness and bronchial asthma might be more prevalent in IBS patients than in control subjects. The aim of our study was to assess the prevalence of IBS in a cohort of asthmatic patients. We evaluated 150 patients with bronchial asthma (71 males and 79 females, aged 45.1+/-14.9 years) and two control groups including 130 patients with other pulmonary disorder and 120 healthy subjects. All subjects enrolled (asthmatic and controls) completed the Greek version of the Bowel Disease Questionnaire (BDQ). BDQ is a, previously validated, self-report instrument to measure gastrointestinal symptoms. Diagnosis of IBS was based on Rome II criteria. The IBS prevalence was significantly higher in asthmatics (62/150, 41.3%) than in subjects with other pulmonary disorders (29/130, 22.3%, P<0.001) and healthy ones (25/120, 20.8%, P<0.001). For all subjects studied, the prevalence of IBS was significantly higher in females (78/214, 36.4%) than in males (38/186, 20.4%, P<0.001). The IBS prevalence in asthmatic males was 29.5% vs. 15.2% in male patients with other pulmonary disorders (P=0.002) and 14.2% in male healthy subjects (P=0.002). The IBS prevalence in asthmatic females was 51.8% vs. 28.1% in females patients with other pulmonary disorders (P<0.001) and 26.5% in females healthy subjects (P<0.001). None of the asthma medications were associated with increased or decreased likelihood of IBS. We conclude that patients with bronchial asthma have an increased prevalence of IBS. Further studies are needed to clarify the potential pathogenetic mechanisms underlying the association between IBS and asthma.
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Affiliation(s)
- A Roussos
- 9th Department of Pulmonary Medicine, SOTIRIA Chest Diseases Hospital, Athens, Greece.
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Affiliation(s)
- Douglas A Drossman
- UNC Center for Functional GI and Motility Disorders, Division of Digestive Diseases, University of North Carolina, Chapel Hill, USA
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Thompson JJ, Elsenbruch S, Harnish MJ, Orr WC. Autonomic functioning during REM sleep differentiates IBS symptom subgroups. Am J Gastroenterol 2002; 97:3147-53. [PMID: 12492202 DOI: 10.1111/j.1572-0241.2002.07112.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to investigate autonomic activity by means of heart rate variability analysis in a sample of irritable bowel syndrome (IBS) patients, allowing stratification into IBS symptom subgroups. METHODS Thirty-three female IBS patients (mean age 37 yr) and 21 healthy female controls (mean age 38 yr) participated. Patients were stratified into 16 subjects with only lower bowel symptoms (IBS only) and 17 subjects with both lower bowel and dyspeptic symptoms (IBS+D). The protocol included standard polysomnography to assess stages of sleep with concomitant electrocardiographic measurement of beat-to-beat intervals of the cardiac cycle. Fifteen-min segments were selected from presleep waking, stage 2 of non-rapid eye movement (REM), and REM sleep and analyzed by spectral analysis of heart rate variability to calculate the high-frequency band, a measure of vagal tone, and the low-frequency/high-frequency ratio, an indicator of sympathovagal balance. RESULTS The high-frequency band power during REM sleep was significantly lower, indicating substantial vagal withdrawal in IBS-only patients compared with IBS+D patients and controls. The low-frequency/high-frequency band ratio was significantly higher during REM sleep for IBS-only patients. CONCLUSIONS IBS-only patients had greater sympathetic dominance, indicated by elevated low-frequency/high-frequency band ratio, during REM sleep because of vagal withdrawal. Autonomic functioning, unique to REM sleep, differentiates IBS symptom subgroups, suggesting that autonomic functioning during REM sleep may be a useful biological marker to identify IBS patient subgroups.
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Abstract
In the United States and other Western cultures, a greater number of women seek health care services for symptoms of functional pain disorders, including irritable bowel syndrome, than men. Recent clinical trials indicate that gender differences in responsiveness to drug therapy also occur. Several lines of inquiry have focused on explaining this gender-related difference due to the higher prevalence of these disorders in women. Evidence of a physiologic component is based on gender differences in gastrointestinal transit time, visceral sensitivity, central nervous system pain processing, and specific effects of estrogen and progesterone on gut function. Additional factors may play a role, including gender-related differences in neuroendocrine, autonomic nervous system, and stress reactivity, which are related to bowel function and pain. However, the link between these measures and gut motility or sensitivity remains to be clarified. Psychological characteristics, including somatization, depression, and anxiety as well as a history of sexual abuse, may also contribute to gender-related differences in the prevalence of irritable bowel syndrome. Although gender differences in the therapeutic benefit of serotonergic agents have been observed, less is known about potential differences in responsiveness to nondrug therapies for irritable bowel syndrome.
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Affiliation(s)
- Lin Chang
- UCLA/CURE Neuroenteric Disease Program, Department of Medicine, and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90073, USA.
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Surrenti E, Ciancio G, Carloppi S, Lucchese M, Coppola A, Caramelli R, Surrenti C. Autonomic nerve dysfunction in pathologically obese patients. Dig Liver Dis 2002; 34:768-74. [PMID: 12546511 DOI: 10.1016/s1590-8658(02)80069-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Obese patients frequently present clinical symptoms related to gastrointestinal motility alterations and autonomic nervous system dysfunction. AIM To evaluate the possible correlation between cardiovascular autonomic nervous dysfunction and oesophageal motility in pathologically obese patients. PATIENTS AND METHODS Enrolled in the study were 22 patients with a body mass index of 45.72 +/- 7.48 and 10 control subjects, all within 20% of their ideal weight. Oesophageal motility was measured by stationary manometry and scintigraphic transit. Tests for the evaluation of autonomic nervous system were: Valsalva ratio, deep breathing, sustained handgrip, sudormotor axon reflex test and spectral analysis of the variability of R-R interval. RESULTS The mean pressure of oesophageal peristaltic waves in patients and controls was 39.36 +/- 14 mmHg and 73 +/- 12 mmHg, respectively The scintigraphic mean transit time was 22.96 +/- 16.26 seconds in patients and 10.23 +/- 16.26 seconds in controls (p < 0.001). Spectral analysis of the variability of the R-R interval showed an increase in the parasympathetic component both in the lying and standing position compared to controls. The other autonomic nervous system function tests showed no significant difference between obese patients and controls. CONCLUSIONS These results suggest that obese patients present a reduction of oesophageal transit and autonomic nervous system dysfunction albeit no direct correlation was found between these phenomena.
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Affiliation(s)
- E Surrenti
- Gastroenterology Unit, Department of Clinical Physiopathology, University of Florence, Azienda Ospedaliera Careggi, Florence, Italy.
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Gschossmann JM, Mayer EA, Miller JC, Raybould HE. Subdiaphragmatic vagal afferent innervation in activation of an opioidergic antinociceptive system in response to colorectal distension in rats. Neurogastroenterol Motil 2002; 14:403-8. [PMID: 12213108 DOI: 10.1046/j.1365-2982.2002.00345.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Abstract In a number of different experimental paradigms of somatic pain, there is evidence for a vagally mediated antinociceptive system. This pathway probably involves opioid mechanisms. However, whether this pathway is activated in visceral pain or if it involves subdiaphragmatic vagal afferents is unclear. The aim of the present study was to determine whether subdiaphragmatic vagal afferents mediate antinociception in response to a visceral stimulus and whether this involves an opioid pathway. Colorectal distension was performed in fasted, conscious male Sprague-Dawley rats using a balloon catheter connected to an electronic distension device. The number of abdominal contractions (visceromotor response) in response to a tonic colorectal distension (60 mmHg for 10 min) was recorded. Experiments were performed in sham or subdiaphragmatically vagotomized, perineural vehicle- or capsaicin-treated rats (to functionally denervate vagal afferents) before and after administration of naloxone (25 mg kg(-1) bodyweight intraperitoneally). Vagotomy, capsaicin and naloxone pretreatments all significantly enhanced the visceromotor response to colorectal distension. The effect of naloxone in capsaicin-treated rats did not appear to be additive. These results suggest that activation of subdiaphragmatic afferents, which can be blocked by capsaicin, may play a role in opioid-dependent antinociceptive pathways activated by a noxious visceral stimulus.
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Affiliation(s)
- J M Gschossmann
- Neuroenteric Disease Program, CURE: Digestive Diseases Research Center, GLA VA HC, Departments of Medicine and Physiology, and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 95616, USA
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Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology 2002; 122:1140-56. [PMID: 11910364 DOI: 10.1053/gast.2002.32392] [Citation(s) in RCA: 773] [Impact Index Per Article: 33.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses. METHODS The scientific literature since 1966 in all languages cited in Medline was systematically reviewed. RESULTS Comorbidity with other functional gastrointestinal disorders is high and may be caused by shared pathophysiological mechanisms such as visceral hypersensitivity. Psychiatric disorders, especially major depression, anxiety, and somatoform disorders, occur in up to 94%. The nongastrointestinal nonpsychiatric disorders with the best-documented association are fibromyalgia (median of 49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%). CONCLUSIONS Multivariate statistical analyses suggest that these are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological. Some models explain the comorbidity of irritable bowel with other disorders by suggesting that each disorder is the manifestation of varying combinations of interacting physiological and psychological factors. An alternative hypothesis is that the irritable bowel diagnosis is applied to a heterogeneous group of patients, some of whom have a predominantly psychological etiology, whereas others have a predominantly biological etiology, and that the presence of multiple comorbid disorders is a marker for psychological influences on etiology.
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Affiliation(s)
- William E Whitehead
- Division of Digestive Diseases and Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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Park DI, Rhee PL, Kim YH, Sung IK, Son HJ, Kim JJ, Paik SW, Rhee JC, Choi KW. Role of autonomic dysfunction in patients with functional dyspepsia. Dig Liver Dis 2001; 33:464-71. [PMID: 11572572 DOI: 10.1016/s1590-8658(01)80023-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The role of autonomic dysfunction in patients with functional dyspepsia is not completely understood. AIMS 1. to prospectively assess abnormalities of autonomic function in patients with functional dyspepsia, 2. to assess whether autonomic dysfunction in these patients is associated with a. visceral hypersensitivity or b. delayed gastric emptying or c. severity of dyspeptic symptoms. PATIENTS A series of 28 patients with functional dyspepsia and 14 healthy volunteers without gastrointestinal symptoms were studied. METHODS All patients and controls were submitted to a battery of five standard cardiovascular autonomic reflex tests, dyspeptic questionnaire, gastric barostat tests and gastric emptying tests. RESULTS 1. Autonomic function tests showed that both sympathetic and parasympathetic scores of dyspeptic patients were significantly higher than in controls; 2. visceral hypersensitivity was confirmed in dyspeptics in response to proximal gastric distension, demonstrating lower pain threshold; 3. delayed gastric emptying occurred more frequently in patients with functional dyspepsia than in controls; 4. epigastric pain and epigastric burning were significantly more prevalent in patients with definite evidence of autonomic dysfunction; 5. No significant association was found between presence of autonomic dysfunction and presence of visceral hypersensitivity or presence of delayed gastric emptying in patients with functional dyspepsia. CONCLUSIONS We concluded that a possible role of autonomic dysfunction in eliciting dyspeptic symptoms could not be determined from alterations in visceral hypersensitivity or delayed gastric emptying. Autonomic dysfunction might not be the major explanation for symptoms associated with functional dyspepsia.
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Affiliation(s)
- D I Park
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Kobayashi S, Ikeda K, Suzuki M, Yamada T, Miyata K. Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo. JAPANESE JOURNAL OF PHARMACOLOGY 2001; 86:281-8. [PMID: 11488427 DOI: 10.1254/jjp.86.281] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
We investigated the effects of YM905 [(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate], a new orally active muscarinic M3-receptor antagonist, on bowel dysfunction in vivo using experimental models that reproduce the symptoms present in irritable bowel syndrome (IBS). YM905 potently inhibited restraint stress-induced fecal pellet output in fed rats (ED50: 4.0 mg/kg) and diarrhea in fasted rats (ED50: 1.7 mg/kg), with similar potencies to the inhibition of bethanechol-, neostigmine- and nicotine-induced fecal pellet output in rats (ED50: 3.3, 7.9 and 4.5 mg/kg, respectively). YM905 also inhibited 5-hydroxytryptamine (5-HT)-, prostaglandin E2- and castor oil-induced secretory diarrhea in mice (ED50: 5.5, 14 and 6.3 mg/kg, respectively), but showed no significant effect on cholera toxin-induced intestinal secretion in mice. In addition, YM905 (3, 10 mg/kg) reversed morphine-decreased postprandial defecation in ferrets, a model of spastic constipation, whereas remosetron, a 5-HT3-receptor antagonist, was not effective. The mode of YM905 action was similar to that of darifenacin, a selective M3-receptor antagonist, with equivalent potencies. By contrast, propantheline, an antimuscarinic drug that has been used for IBS, was much less potent. These results show that YM905 ameliorates a wide spectrum of bowel dysfunctions through the blockade of M3 receptors, suggesting its therapeutic potential for treating IBS.
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Affiliation(s)
- S Kobayashi
- Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba-shi, Ibaraki, Japan.
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Yazar A, Atis S, Konca K, Pata C, Akbay E, Calikoglu M, Hafta A. Respiratory symptoms and pulmonary functional changes in patients with irritable bowel syndrome. Am J Gastroenterol 2001; 96:1511-6. [PMID: 11374691 DOI: 10.1111/j.1572-0241.2001.03748.x] [Citation(s) in RCA: 83] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Scientific evidence of functional interface between the immune and sensory motor systems of the gut and respiratory systems has been reported. In recent studies excess prevalence of bronchial hyper-responsiveness has been shown among patients with irritable bowel syndrome (IBS). The purpose of our study was to investigate the possible relationship between IBS and asthma. METHODS One hundred thirty-three patients with IBS (108 women, 25 men) and 137 control subjects (105 women, 32 men) were included in this study. Both for IBS and the control group, the mean ages were 41.64+/-9.45 yr and 39.94+/-10.62 yr, respectively. Patients more than 50 yr old, with any organic GI disease, acute respiratory system infection, current or ex-smokers, and patients using drugs affecting smooth muscle and autonomic nervous system were not included in the study. Respiratory symptoms were questioned and pulmonary function tests were performed for every subject. RESULTS There were 45 (33.8%) and eight (5.8%) subjects with respiratory symptoms in IBS and control groups, respectively (p < 0.0001). Twenty-one (15.8%) patients from the IBS group and two (1.45%) patients from the control group had the diagnosis of asthma according to history, clinical, and PFT findings. There was no statistical difference between two groups with respect to percentage of forced vital capacity and forced expiratory volume in 1 s-to-forced vital capacity. The difference between the two groups in forced expiratory volume in 1 s, flow after 50% of the vital capacity has been exhaled, peak expiratory flow rate, and maximal mid-expiratory flow rate was statistically significant (p < 0.01). CONCLUSION We found that the prevalence of asthma was more common in the IBS group than in controls. Our finding supports the speculation that asthma and IBS may share common pathophysiological processes.
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Affiliation(s)
- A Yazar
- Department of Internal Medicine, Mersin University Faculty of Medicine, Turkey
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Elsenbruch S, Orr WC. Diarrhea- and constipation-predominant IBS patients differ in postprandial autonomic and cortisol responses. Am J Gastroenterol 2001; 96:460-6. [PMID: 11232691 DOI: 10.1111/j.1572-0241.2001.03526.x] [Citation(s) in RCA: 108] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE As the primary link between brain and gut, autonomic and endocrine dysfunction may play a role in the pathophysiology of the irritable bowel syndrome (IBS). The aim of this study was to assess autonomic, endocrine, and symptomatic responses to food intake in diarrhea-predominant and constipation-predominant IBS patients, compared to normals. METHODS Twelve women with diarrhea-predominant or alternating IBS (IBS-D), 12 women with constipation predominant IBS (IBS-C), and 20 healthy women participated. GI symptoms, saliva cortisol concentration, heart rate, and heart rate variability were assessed at baseline and after a meal. Spectral analysis of heart rate variability was used as a measure of the sympathovagal regulation of the heart rate. RESULTS Both groups of IBS patients showed a significant postprandial increase in GI symptoms. IBS-D showed a significant increase in the low frequency/high frequency band ratio and a decrease in the high frequency band power during the first postmeal period, which was significantly different, not only from controls, but also from IBS-C. IBS-D also showed a significant postprandial increase in cortisol, which was not evident in controls or IBS-C. There was a significant correlation between the vagal response and the postprandial increase in GI symptoms in IBS-D (r = 0.6, p < 0.05). CONCLUSIONS These findings support the notion that the IBS symptom groups are characterized by different physiological responses to visceral stimuli, and point to a role of autonomic pathways in IBS symptomatology.
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Affiliation(s)
- S Elsenbruch
- Institute for Medical Psychology, University Clinic of Essen, Germany
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Abstract
Women seek healthcare and are diagnosed more frequently with chronic somatic and visceral pain conditions relative to men. These conditions tend not to be life-threatening disorders, but rather ones that decrease people's quality of life, impinge on work and recreational activities, and increase healthcare resource utilization. With increased awareness of basic gender differences in biology and responsiveness to therapies, there has been renewed interest in factors which may account for the gender disparity in chronic visceral pain conditions. Basic and clinical evidence primarily from patients with irritable bowel syndrome has provided initial insights into visceral pain sensitivity, perception, and responsitivity.
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Affiliation(s)
- M M Heitkemper
- Department of Biobehavioral Nursing and Health Systems, Box 357266, University of Washington, 1959 NE Pacific Street, T 618, Seattle, WA 98195, USA.
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Orr WC, Elsenbruch S, Harnish MJ. Autonomic regulation of cardiac function during sleep in patients with irritable bowel syndrome. Am J Gastroenterol 2000; 95:2865-71. [PMID: 11051361 DOI: 10.1111/j.1572-0241.2000.02318.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Several studies have provided evidence of abnormal autonomic activity in irritable bowel syndrome (IBS), suggesting that abnormal central nervous system-autonomic nervous system arousal mechanisms may be part of its pathophysiology. The goal was to investigate cardiac sympatho-vagal balance during waking and the different stages of sleep using heart rate variability analysis in IBS patients compared to healthy controls. METHODS A total of 15 IBS patients (13 female, two male, mean age 34.9 +/- 2.1 yr) and 15 controls (13 female, two male, mean age 36.2 +/- 2.3 yr) were studied during 1 h of pre-sleep quiet waking and during seven-hours of sleep. Polysomnography was used for the determination of state of consciousness. Electrocardiography provided the beat-to-beat intervals, which were then subjected to spectral analysis for determination of the percentage of energy in the low and high frequency bands, respectively. The low frequency/high frequency band ratio was also calculated. For each subject, heart rate variability analysis was performed using 15-min segments of waking, non-rapid eye movement sleep, and rapid eye movement sleep. RESULTS The low frequency band power was significantly greater in IBS patients during waking. No group differences were found in high frequency band power during any state. The low frequency to high frequency band ratio was significantly greater in IBS patients during rapid eye movement sleep. CONCLUSIONS IBS patients have greater sympathetic activity during waking and greater overall sympathetic dominance during rapid eye movement sleep. These results support the presence of autonomic abnormalities in patients with IBS. The possibility is discussed that sympathetic dominance during rapid eye movement sleep may play a role in sensitizing the gut to waking stimulation.
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Affiliation(s)
- W C Orr
- Lynn Institute for Healthcare Research, Oklahoma City, Oklahoma 73112, USA
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Read NW. Bridging the gap between mind and body: do cultural and psychoanalytic concepts of visceral disease have an explanation in contemporary neuroscience? PROGRESS IN BRAIN RESEARCH 2000; 122:425-43. [PMID: 10737075 DOI: 10.1016/s0079-6123(08)62155-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Affiliation(s)
- N W Read
- Centre for Human Nutrition, Northern General Hospital, University of Sheffield, UK.
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Karling P, Nyhlin H, Wiklund U, Sjöberg M, Olofsson BO, Bjerle P. Spectral analysis of heart rate variability in patients with irritable bowel syndrome. Scand J Gastroenterol 1998; 33:572-6. [PMID: 9669625 DOI: 10.1080/00365529850171800] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Autonomic dysfunction, both adrenergic and cholinergic, has been associated with the irritable bowel syndrome (IBS). The accuracy of the methods in use, however, has been limited by the need for active co-operation by the patients, with consequent difficulties in standardization. The aim of this study was to investigate the function of the autonomic nervous system in patients with IBS by using spectral analysis of the heart rate variability, an accurate method depending very little on patient cooperation. METHODS Eighteen patients with IBS were compared with 36 sex- and age-matched controls. Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic nerve activity. RESULTS The patients with IBS had significantly higher sympathetic activity than controls (P = 0.005). There was no significant (P = 0.308) increase in parasympathetic activity. There were no significant differences in heart rate or blood pressure between the patients and controls. CONCLUSION Spectral analysis of heart rate variability has been used to assess the function of the autonomic nervous system in patients with IBS. IBS patients have significantly increased symphathetic activity, whereas parasympathetic activity does not differ from that of controls.
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Affiliation(s)
- P Karling
- Dept. of Internal Medicine, Umeå University Hospital, Sweden
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