Pathophysiology underlying irritable bowel syndrome -From the viewpoint of dysfunction of autonomic nervous system activity-

Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Japan.
Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi 03/2009; 45(1):15-23. DOI: 10.1540/jsmr.45.15
Source: PubMed


Although irritable bowel syndrome (IBS) is the most common gastrointestinal disease and is found in up to 50% of patients referred to gastroenterologists, its pathogenesis remains unexplained. Lately most attention has been focused on visceral hypersensitivity related to dysfunction of the autonomic nervous system. Although there have been many reports regarding the autonomic nervous system in IBS patients, the results have not always been consistent. In many studies, increased sympathetic nervous system activity and decreased parasympathetic nervous system activity have been the most frequently noted differences when IBS patients are compared with healthy controls. There are also some differences among IBS symptom subgroups and some differences between men and women. Data from previous studies have been inconsistent, with complicating factors resulting in difficulties in classification and the possibility of multiple physiological pathways for a similar symptom picture. Further studies based on the Rome III criteria are required to evaluate whether or not autonomic functions significantly differ from each other. However, although there are many methods of measurement for evaluation of the autonomic nervous system, there are few of these methods that are not only accurate but also cost-effective, non-invasive, and easy to perform. Recently, we developed a new method with the abovementioned advantages for measuring fingertip blood flow in evaluating the autonomic nervous system by continuous-wave Doppler sonography. Using this method, we found that abnormal fingertip blood flow responses suggested the presence of excess sympathetic activity.

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    • "Stress has been implicated in both illness cause, and also in symptom exacerbation [15] [16]. IBS has generally been associated with increased sympathetic nervous system (SNS) activity and decreased parasympathetic nervous system (PNS) activity [17] [18] [19] [20], yet, the inverse [21] [22], and also no autonomic irregularities have been reported [23] [24]. Skin conductance response (SCR) has a long history of use as an indicator of SNS activity [23] [25]. "
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    ABSTRACT: Objective : To determine if cognitive processing, and subjective and physiological responses to stress and relaxation differed between an irritable bowel syndrome (IBS) group and control group. How these variables relate to the severity of IBS symptoms was also determined. Methods : Twenty-one IBS participants and 20 controls provided cognitive (attention and processing), subjective (perceived stress and vigour), and physiological (heart rate, blood pressure, and skin conductance) data during a relaxation and stress phase. Logistic regression analyses determined which variables related to the IBS group and hierarchical linear regression assessed how the variables related to the severity of IBS symptoms. Results : Subjective and cognitive factors (drowsiness at baseline, total vigour, and reduced Stroop colour-naming accuracy for negative words) significantly related to IBS, χ2 (3, N = 41) = 23.67, p < .001, accurately categorising 85% of participants. IBS symptom severity was associated with both subjective (drowsiness at baseline and a smaller reduction in tiredness from relaxation to stress) and physiological (smaller increase in systolic blood pressure from baseline to stress phase and lower skin conductance at baseline) variables. This model predicted IBS severity, F (4, 16) = 11.20, p < .001, and accounted for 74% of the variability in scores. Conclusions : A negative attention bias, which may be related to a negative self-schema, as well as perceived low vigour were important in categorising IBS. Low subjective vigour and reduced physiological reactivity to both relaxation and stress conditions was associated with IBS severity, suggestive of illness-related allostatic load.
    Journal of Psychosomatic Research 07/2014; 77(1). DOI:10.1016/j.jpsychores.2014.04.009 · 2.74 Impact Factor
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    • "Increased sympathetic and decreased parasympathetic activity is an essential element of the body’s response to stress. Stress and affective states cause sympathetic activation and therefore subsequent IBS manifestations [22]. Iovino et al. showed that activation of the sympathetic nervous system increased perception of intestinal wall stretching, which could explain the frequent complaints of pain and feeling of inflating intestines reported by IBS patients [23]. "
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    ABSTRACT: 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. 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. 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. Central sympathetic influence within the brain-gut axis is most probably responsible for myoelectrical activity disturbances in irritable bowel syndrome patients.
    Medical science monitor: international medical journal of experimental and clinical research 08/2012; 18(8):CR493-499. DOI:10.12659/MSM.883269 · 1.43 Impact Factor
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    • "According to The Rome Committee for the classification of functional gastrointestinal disorders, IBS is characterized by recurrent abdominal pain or discomfort, change in the frequency of stool form, bloating, abnormal bowel habits (diarrhea, constipation or a combination of both) and related symptoms (Crowell et al., 2005; Sohrabi et al., 2010; Spiegel et al., 2010). These symptoms are thought to be associated with a disturbance of the brain-gut axis which contributes to visceral hypersentivity and dysmotility (Akbar et al., 2009; Manabe et al., 2009). The exact etiology of IBS is multi-factoral, including psychological stress (Barreau et al., 2007; Miranda, 2009), environmental factors, genetic predisposition, and diet (Morcos et al., 2009; Saito et al., 2009; Talley, 2006). "
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    ABSTRACT: Coptis chinensis rhizomes (Coptidis Rhizoma, CR), also known as "Huang Lian", is a common component of traditional Chinese herbal formulae used for the relief of abdominal pain and diarrhea. Yet, the action mechanism of CR extract in the treatment of irritable bowel syndrome is unknown. Thus, the aim of our present study is to investigate the effect of CR extract on neonatal maternal separation (NMS)-induced visceral hyperalgesia in rats and its underlying action mechanisms. Male Sprague-Dawley rats were subjected to 3-h daily maternal separation from postnatal day 2 to day 21 to form the NMS group. The control group consists of unseparated normal (N) rats. From day 60, rats were administrated CR (0.3, 0.8 and 1.3 g/kg) or vehicle (Veh; 0.5% carboxymethylcellulose solution) orally for 7 days for the test and control groups, respectively. Electromyogram (EMG) signals in response to colonic distension were measured with the NMS rats showing lower pain threshold and increased EMG activity than those of the unseparated (N) rats. CR dose-dependently increased pain threshold response and attenuated EMG activity in the NMS rats. An enzymatic immunoassay study showed that CR treatment significantly reduced the serotonin (5HT) concentration from the distal colon of NMS rats compared to the Veh (control) group. Real-time quantitative PCR and Western-blotting studies showed that CR treatment substantially reduced NMS induced cholecystokinin (CCK) expression compared with the Veh group. These results suggest that CR extract robustly reduces visceral pain that may be mediated via the mechanism of decreasing 5HT release and CCK expression in the distal colon of rats.
    Journal of ethnopharmacology 06/2011; 135(3):754-61. DOI:10.1016/j.jep.2011.04.007 · 3.00 Impact Factor
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