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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.

Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.

Computerized auscultation of the abdomen provides a noninvasive and quantitative method to investigate gastrointestinal function. Two-dimensional mapping of bowel sound sites of origin, to the surface of the abdomen, was accomplished through simultaneous recording with three electronic stethoscopes. Control, irritable bowel syndrome, and nonulcer dyspepsia groups were studied. The predominant site of fasting sound production was the right lower quadrant in all except a subgroup of nonucler dyspepsia patients. The second most common site mapped to the area of the stomach. The region mapping to the small intestine was largely devoid of sound. The control group had a higher percentage of sounds in the 184- to 248-Hz range than the functional bowel patients (P < 0.001) for sounds mapping to the stomach region. We conclude that two-dimensional mapping may have the potential to allow for the meaningful and objective categorization of groups of functional bowel patients.

The gastrointestinal tract is a complex ecosystem host to a diverse and highly evolved microbial community composed of hundreds of different microbial species. The interactions that occur between this complex microbial community and the human host have become the focus of scientific research due to increases in the incidence of illnesses associated with deficient or compromised microflora (e.g., gastrointestinal tract infections, inflammatory bowel disease (Crohn's disease and ulcerative colitis), irritable bowel syndrome, antibiotic-induced diarrhea, constipation, food allergies, cardiovascular disease, and certain cancers). Effective multidisciplinary research programs now complement conventional microbiology with molecular ecology techniques to provide culture-independent analysis of the gastrointestinal ecosystem. Furthermore, as we acquire an understanding of gut microflora composition and processes such as intestinal adherence, colonization, translocation, and immunomodulation, we are also elucidating mechanisms by which these can be influenced. This knowledge not only allows scientists to define the activities and interactions of "functional food"-borne beneficial bacteria in the gut, but will also provide the scientific basis for the development of innovative biotechnology-based products tailored to prevent specific diseases and promote overall human gastrointestinal health.

Different types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.

This report highlights various considerations regarding the potential effects of concurrent psychiatric conditions and a history of abuse in patient volunteers for clinical trials in irritable bowel syndrome (IBS). Even though many studies have used psychological rating scales to assess personality and psychological traits of patients with IBS, the prevalence of the different psychiatric diagnoses (i.e., categorical assessment) in patients with IBS has only recently been assessed systematically. Recent studies of treatment-seeking patients have indicated that the majority of individuals (50% to 90%) who seek treatment for IBS have a lifetime history or currently have one or more common psychiatric conditions: major depressive disorder, generalized anxiety disorder, panic disorder, social phobia, somatization disorder, and posttraumatic stress disorder. Traditional clinical wisdom is that the presence of a psychiatric disorder increases the likelihood that an IBS patient will seek treatment. However, recent data suggest that IBS and psychiatric disorders are associated regardless of treatment-seeking status. Patients with psychiatric disorders should be included in clinical IBS studies, because this reflects the actual patient population. Extrapolating from the psychiatric literature, inclusion of patients with IBS with mild to moderate anxiety or depression is warranted.

Current concepts and basic principles of neurogastroenterology in relation to functional gastrointestinal disorders are reviewed. Neurogastroenterology is emphasized as a new and advancing subspecialty of clinical gastroenterology and digestive science. As such, it embraces the investigative sciences dealing with functions, malfunctions, and malformations in the brain and spinal cord, and the sympathetic, parasympathetic and enteric divisions of the autonomic innervation of the digestive tract. Somatomotor systems are included insofar as pharyngeal phases of swallowing and pelvic floor involvement in defecation, continence, and pelvic pain are concerned. Inclusion of basic physiology of smooth muscle, mucosal epithelium, and the enteric immune system in the neurogastroenterologic domain relates to requirements for compatibility with neural control mechanisms. Psychologic and psychiatric relations to functional gastrointestinal disorders are included because they are significant components of neurogastroenterology, especially in relation to projections of discomfort and pain to the digestive tract.

Endogenous opioid peptides - enkephalins, beta-endorphin and dynorphins - are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. The mu receptor agonists - morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide - have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials.

Despite their high prevalence and significant economic impact on the healthcare system, functional GI disorders have evaded successful therapy. Conventional medical therapies are based on inadequate disease models, and the great majority of published treatment trials are flawed in their design, thus not permitting to draw any conclusions about true efficacy of any particular treatment. The past several years have seen the rapid evolution of a new, comprehensive disease model, based on alterations in brain-gut interactions. Even though the precise mechanisms and sites underlying these alterations remain incompletely understood, plausible targets for the development of effective pharmacologic treatment are receptors on peripheral terminals of visceral afferent nerves (opioids, serotonin), ion channels and receptors on dorsal horn neurons within the spinal cord (opioids, glutamate, CGRP, NK-1) and supraspinal targets in the brainstem, within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine, acetylcholine). Regardless of the primary pathophysiology underlying functional GI disorders (i.e. central vs. peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may be effective.

The irritable bowel syndrome (IBS) is very common in the community. Psychosocial factors other than the gut symptoms themselves may contribute to the decision of a few to seek medical care. Examination of these not only suggests that the manifestation of symptoms is multifactorial, but also offers clues for management of individuals. There is evidence for both physical and psychological contributions to IBS symptoms and both together may induce illness behavior. In some, many factors may be present, in others apparently none, but the more factors at work, the more complex the treatment. Management should take advantage of the known features of the disease. Its prevalence, recognizable symptoms, and benign nature underpin the reassurance value of a positive diagnosis. Psychopathology or antecedent stressful life events may indicate psychological treatments. Although drugs are unproved in the global treatment of IBS, certain agents may benefit specific symptoms and use the placebo response to advantage. Patients having more difficulty treating symptoms need continuing care. A graded response to IBS complaints implies reassurance and drug-free management in primary care, with increments of psychosocial support, psychotherapy, and the specific use of drugs in nonresponders. The goal for intractable cases should be improved functioning rather than cure.

Functional abnormalities of the digestive tract and the gallbladder in irritable bowel syndrome (IBS) are described in this review. In addition to colonic abnormalities, disordered oesophageal motility, abnormal gastric emptying, abnormalities in small intestinal motility and abnormal gall bladder function have been demonstrated in IBS. Urodynamic abnormalities and bronchial hyperreactivity also have been reported in patients with IBS. Such extensive involvement of the organs suggests that IBS can be a generalized abnormality of the smooth muscle of even the whole body as well as the whole digestive tract. Further detailed investigation is needed to clarify this possibility.

The pattern of gastrointestinal symptoms and select mood and somatic symptoms was examined across two menstrual cycles in women with (n = 19) and without (n = 39) functional bowel distress (FBD). The women (a) rated their gastrointestinal, perimenstrual, mood, and other symptoms and stool frequency and consistency daily; (b) completed the Menstrual Distress Questionnaire-T; and (c) had serum levels of estrogen and progesterone measured during the menses, follicular, and luteal phases. Stomach pain, nausea, and diarrhea were rated higher at menses in the group with FBD than in the group without FBD. Stomach pain was higher during the remaining days as well. The group with FBD reported higher levels of perimenstrual symptoms also on six of the eight Menstrual Distress Questionnaire-T subscales (P less than 0.01). Other complaints, e.g., poor work/school performance, were higher in women with FBD, but somatic symptoms that were expected to vary over the cycle did not differ between groups, except cramping pain. There were no significant group differences in ovarian hormone levels or stool consistency/frequency scores.

Intestinal transit time was studied in two groups of 8 patients with irritable colon. In the first group, the time was longer than normal, whereas in the second it was accelerated. Three subjects in each group received a placebo, while the other five received 60 mg/day bromopride for 15 days. No change in transit time was noted in the controls. Two subjects in Group I displayed a significant reduction in transit time after bromopride, while deceleration and normalisation were observed in 4/5 patients in Group II.

The article presents some individual perceptions of the nature of the disease we call the Irritable Bowel Syndrome (IBS), and attempts to rationalise the variable presenting features, the influence of the psyche and the lack of pathological or biochemical markers. Among the topics discussed include the existence of recognisable subsets of the disease, the influence of mental stress, and the pathophysiology of the presenting symptoms. My impression is that IBS is a condition, in which the gut is hypersensitive and hyper-reactive to mechanical and chemical stimuli and as such, can be compared with asthma in the respiratory system. This hyper-reactivity could be caused by increased mucosal permeability, increased numbers and/or responses of effector cells such as mast cells or enterochromaffin cells, and enhancement of intrinsic nerve reflexes by increased activity of efferent vagal fibres.