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Applied Principles of Neurogastroenterology: Physiology/Motility Sensation

2006; Elsevier BV; Volume: 130; Issue: 5 Linguagem: Inglês

10.1053/j.gastro.2005.08.061

1528-0012

John Kellow, Fernando Azpiroz, Michel Delvaux, Gerald F. Gebhart, Howard R. Mertz, Eamonn M.M. Quigley, A. J. P. M. Smout,

Diet and metabolism studies

Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made. Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made. The digestive tract is fitted with a complex wiring system that modulates its response to the internal and external environment. The 2 aspects of gut physiology most relevant to the functional gastrointestinal disorders (FGIDs) are sensation and motility. In health, physiological stimuli from the gut induce motor reflexes, but these remain largely unperceived, with the exception of those related to ingestion and excretion. Visceral afferent pathways, however, also serve as an "alarm" system to induce conscious perception when appropriate. Gut motility, encompassing myoelectrical activity, phasic contractions, tone, compliance, accommodation, and transit, is regulated by reflex mechanisms and is intimately related to gut sensitivity. In the FGIDs, sustained and inappropriate gut hypersensitivity, as well as gut dysmotility, are well documented. These sensory-motor dysfunctions seem related to alterations in neural processing in the brain-gut axis and in visceral reflex pathways. Their underlying causes and their relevance to symptom generation are the subject of ongoing research. The aim of this article is to summarize the key principles of applied neurogastroenterology as they relate to the FGIDs. Although sensation refers to a conscious experience, the term sensitivity, when applied to the gastrointestinal tract, has been used to refer both to conscious perception of gut stimuli and to afferent input within gastrointestinal sensory pathways, whether related to perception or to reflex responses. For the purpose of this review, the term sensitivity is restricted to the processes leading to conscious perception. Unlike other tissues in the body, the viscera are unique in that each organ is innervated by 2 sets of nerves, vagal and splanchnic spinal nerves or pelvic and splanchnic spinal nerves. Both systems participate in the reflex control of gut function, but their involvement in sensation differs.1Bielefeldt K. Gebhart G.F. Visceral pain—Basic mechanisms.in: Koltzenburg M. McMahon S. Textbook of pain. 5th ed. Churchill-Livingstone, New York2005: 721-726Google Scholar Discomfort and pain from the gastrointestinal tract are conveyed to the central nervous system (CNS) principally by spinal afferents. Activation of vagal afferents is not considered to give rise to sensations perceived as pain; their activation may, however, modulate spinal visceral (and somatic) pain. From second-order neurons in the spinal dorsal horn, which receive direct input from spinal visceral afferent fibers, visceral sensory information is conveyed to supraspinal sites and finally to cortical areas in which conscious perceptions arise. Perception pathways can be activated in healthy subjects by mechanical distention of the gut, but the final conscious perception is modulated by various interacting factors. For instance, intestinal nutrients, especially fat, enhance such perception.2Evans P.R. Kellow J.E. Physiological modulation of jejunal sensitivity in health and in the irritable bowel syndrome.Am J Gastroenterol. 1998; 93: 2191-2196Crossref PubMed Scopus (29) Google Scholar, 3Accarino A.M. Azpiroz F. Malagelada J.-R. Modification of small bowel mechanosensitivity by intestinal fat.Gut. 2001; 48: 690-695Crossref PubMed Scopus (53) Google Scholar In addition to mechanosensitive structures and polymodal endings, the viscera are innervated by a group of mechanically insensitive afferent fibers. Normally, these endings in the viscera are unresponsive ("silent") to mechanical stimulation, but, after organ insult, acquire spontaneous activity and mechanosensitivity and contribute significant input to the CNS. Increases in neuron excitability both peripherally and in the spinal cord lead to visceral hypersensitivity, a characteristic feature of the FGIDs. Neurons in supraspinal sites also exhibit increases in excitability, particularly in brain areas associated with descending modulation of spinal sensory transmission.1Bielefeldt K. Gebhart G.F. Visceral pain—Basic mechanisms.in: Koltzenburg M. McMahon S. Textbook of pain. 5th ed. Churchill-Livingstone, New York2005: 721-726Google Scholar These modulatory circuits can be influenced in turn by cognitive, affective, and stressful influences, as well as by expectation and prior experience. The major functions of human digestive tract motility are to accomplish propulsion along the gut, to mix gut contents with digestive secretions and expose them to the absorptive surface, to facilitate temporary storage in certain regions of the gut, to prevent retrograde movement of contents from one region to another, and to dispose of residues. Motility is controlled by reflexes, both central and peripheral, as well as by descending modulation from the brain-gut axis. Communication between various regions of the gut is facilitated by the transmission of myogenic and neurogenic signals longitudinally along the gut.4Sarna S.K. Myoelectrical and contractile activities of the gastrointestinal tract.in: Schuster M.M. Crowell M.D. Koch K.L. Schuster atlas of gastrointestinal motility in health and disease. 2nd ed. BC Decker Inc, Hamilton2002: 1-18Google Scholar Gastrointestinal contractions may be classified on the basis of their duration; contractions may be of short duration (phasic contractions) or may be more sustained (tone). Tone is clearly recognized in organs with reservoir function, such as the proximal stomach (accommodation response to a meal) and the colon (response to feeding), as well as in sphincter regions. Compliance refers to the capability of a region of the gut to adapt to its content; it is expressed as the ratio of the change in volume to the change in pressure and is obtained from the pressure-volume curve. Compliance reflects the contribution of several factors, including the capacity (diameter) of the organ, the resistance of surrounding organs, the elastic properties of the gut wall, and its muscular activity. Wall tension, related to compliance, describes the force acting on the gut wall and results from the interaction between intraluminal content and the elasticity of the wall. Gut sensation is influenced by tonic or phasic contractions, and several observations suggest that this is mediated in part by an effect on wall tension; assessment of wall tension is therefore important in the interpretation of results of tests assessing perception of visceral stimuli. Transit refers to the time taken for intraluminal contents to traverse a specified region of the gastrointestinal tract. It reflects the combined effects of the various phenomena outlined earlier. Most measurements of transit are based on detecting intraluminal movements of an extrinsic marker labelling the luminal content. Transit depends on many factors, such as the physical (eg, solid, liquid, and gas) and chemical (eg, pH, osmolality, and nutrient composition) nature of both gut contents and the administered marker. Measurement of transit is influenced by the state of gut motility at the time of marker administration (eg, fasted vs fed motility) and any preparation of the gut (eg, cleansing of the colon). In the context of the FGIDs, gastrointestinal dysmotility can develop through dysfunction of the control mechanisms at any level from the gut to the CNS. For example, inflammatory, immune, infiltrative, degenerative, or other processes may directly affect the muscle and/or other elements of the enteric nervous system, whereas psychosocial stressors can induce profound alterations in motility. Because patients with FGID tend to have a greater gastrointestinal motor response to stressful conditions than do healthy subjects, psychosocial stressors are particularly relevant to the symptomatic manifestations of the FGIDs. The presence of altered visceral sensitivity and/or enteric dysmotility is usually evaluated by measuring responses to test stimuli applied to the gut under various physiological and nonphysiological experimental conditions. This form of provocative testing involves 3 key components: stimulation type and technique, measurement of the responses, and modulatory factors that may affect the responses (Figure 1). Physiological stimuli, such as orally or intraluminally administered nutrients, can be used to study reflex motor responses, but supraphysiological stimuli, such as gut distention or overloading with nutrients, are required to activate sensory pathways and induce perception. Various paradigms can be used to blind the stimuli and make them less predictable.5Whitehead W.E. Delvaux M. Standardization of procedures for testing smooth muscle tone and sensory thresholds in the gastrointestinal tract.Dig Dis Sci. 1997; 42: 223-241Crossref PubMed Scopus (362) Google Scholar A range of responses to gut stimulation can be measured, including conscious perception, afferent signalling within the brain and spinal cord, gut motor activity, and autonomic responses. Assessment of conscious perception includes the quality, intensity, and affective dimensions, as well as the location and referral of the perceived sensations. A rating scale such as a visual analog scale or threshold detection paradigms (ie, the magnitude of stimulus required to reach a certain level of perception, such as discomfort or pain) can be used. Detection of afferent signals within the brain can be achieved using a variety of techniques, including cortical-evoked potentials, magnetoencephalography, positron-emission tomography, functional magnetic resonance imaging, and single-photon–emission computed tomography.6Aziz Q. Thompson D.G. Brain-gut axis in health and disease.Gastroenterology. 1998; 114: 559-578Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar Similarly, a variety of recording techniques can be used to measure digestive tract motor activity during basal conditions and in response to stimuli; the latter also enables testing of specific enteric reflexes (Table 1). In the absence of a widely accepted and convenient test of visceral autonomic integrity, autonomic responses to visceral stimuli are usually measured with tests of primarily cardiac autonomic innervation, such as heart rate variability;7Tougas G. The autonomic nervous system in functional bowel disorders.Gut. 2000; 47: iv78-iv81Crossref PubMed Scopus (81) Google Scholar it is not known, however, whether this measurement is representative of other autonomic responses to gut stimuli. Finally, different types of responses can be evaluated simultaneously and correlated (eg, conscious perception and motor or autonomic reflexes).Table 1Measurement of Gastrointestinal Motor ResponsesRecording techniquesMain applicationsI. Transit Radio-opaque markers and x-rayaMost widely available techniques. Modified and reprinted with permission.75Gastric emptying, colonic transit Hydrogen breath testsaMost widely available techniques. Modified and reprinted with permission.75Orocecal transit ScintigraphyaMost widely available techniques. Modified and reprinted with permission.75Esophageal transitGastric emptyingSmall bowel and colonic transitBile flowDynamics of defecation Labelled C-substrate breath testsaMost widely available techniques. Modified and reprinted with permission.75Gastric emptyingOrocecal transit Magnetic resonance imagingGastric emptying Pharmacologic markers AcetaminophenGastric emptying of liquids SulfasalazineOrocecal transit time Intraluminal impedance monitoringEsophageal transitII. Reflux X-rayaMost widely available techniques. Modified and reprinted with permission.75Gastroesophageal reflux Scintigraphy pH monitoringaMost widely available techniques. Modified and reprinted with permission.75 Bilirubin absorbance monitoring Intraluminal impedance monitoringIII. Wall motion UltrasonographyAntropyloric contractionsGastric areas and volumeGallbladder volume ScintigraphyAntral contractions Magnetic resonance imagingAntral contractions SPECTGastric accommodationIV. Intraluminal pressure Water-perfused manometryaMost widely available techniques. Modified and reprinted with permission.75Phasic contractions and sphincter Solid-state transducersTone at all levels of the digestive tractV. Myoelectrical activity ElectrogastrographyGastric surface electrical activity Intraluminal electromyographyGastric, small intestinal, and colonic electrical activity Needle electromyographyAnal sphincter and pelvic floor muscle activityVI. Tone, compliance & wall tension BarostatTone and compliance at all levels of the Gl tracta Most widely available techniques. Modified and reprinted with permission.75Rome II: the functional gastrointestinal disorders. Drossman DA, ed. 2nd ed. McLean, VA: Degnon Associates, Inc, 2000. http://www.romecriteria.org.Google Scholar Open table in a new tab Many factors, both local and extraintestinal, can modify the previously described responses to stimuli and require attention in the testing of sensorimotor function. For example, anticipatory knowledge increases perception of gut distention,8Accarino A.M. Azpiroz F. Malagelada J.-R. Attention and distraction effects on gut perception.Gastroenterology. 1997; 113: 415-422Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar whereas anxiety and fear of impending pain can trigger brain activation patterns similar to those evoked by actual rectal stimulation.9Naliboff B.D. Derbyshire S.W.G. Munakata J. et al.Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation.Psychosom Med. 2001; 63: 365-375PubMed Google Scholar Some tests are designed specifically to evaluate these modulatory mechanisms.10Azpiroz F. Gastrointestinal perception pathophysiological implications.Neurogastroenterol Motil. 2002; 14: 1-11Crossref Scopus (48) Google Scholar Hypersensitivity to distention affecting various regions of the gastrointestinal tract has been a consistent finding in many FGIDs; there appears to be some specificity for individual FGIDs, at least with respect to the organ considered most relevant in the pathophysiology of the disorder.11Bouin M. Lupien F. Riberdy M. et al.Intolerance to visceral distention in functional dyspepsia or irritable bowel syndrome an organ-specific defect or a pan-intestinal dysregulation?.Neurogastroenterol Motil. 2004; 16: 311-314Crossref PubMed Scopus (70) Google Scholar Likewise, abnormal motor responses to gut stimuli have frequently been documented in the FGIDs. Sensory and motor dysfunctions may interact to produce symptoms, the specific clinical syndrome depending on the pathways, and territories affected, but these aspects require further study. In functional dyspepsia (FD), gastric hypersensitivity, delayed gastric emptying, and impaired accommodation of the proximal stomach have been well documented, but the prevalence of these abnormalities (around 50%) depends on the population studied. Impaired gastric accommodation has been shown to not necessarily be associated with gastric hypersensitivity, delayed gastric emptying, or the presence of Helicobacter pylori;12Tack J. Piessevaux H. Coulie B. et al.Role of impaired gastric accommodation to a meal in functional dyspepsia.Gastroenterology. 1998; 115: 1346-1352Abstract Full Text Full Text PDF PubMed Scopus (947) Google Scholar in this latter study, the symptom of early satiety was independently associated with impaired accommodation. In a scintigraphic study13Piessevaux H. Tack H. Walrand S. et al.Intragastric distribution of a standardized meal in health and functional dyspepsia; correlation with specific symptoms.Neurogastroenterol Motil. 2002; 124: 903-910Google Scholar of the intragastric distribution of a meal, early satiety was correlated with early redistribution of liquids to the antrum, whereas the symptom of fullness was correlated with late proximal gastric retention. The reproducibility of hypersensitivity appears to be greatest with fundic distention in patients with postprandial symptoms and with antral distention in pain-predominant FD patients, whereas nutrients exaggerate the gastric hypersensitivity.14Caldarella M.P. Azpiroz F. Malagelada J.-R. Antro-fundic dysfunctions in functional dyspepsia.Gastroenterology. 2003; 124: 1220-1229Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar Normally, antral filling elicits a reflex relaxation of the proximal stomach that contributes to meal accommodation. Accommodation is then further modulated by enterogastric reflexes depending on the load and composition of intestinal chyme. Impaired gastrogastric and enterogastric reflexes in dyspepsia14Caldarella M.P. Azpiroz F. Malagelada J.-R. Antro-fundic dysfunctions in functional dyspepsia.Gastroenterology. 2003; 124: 1220-1229Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar may result in a defective relaxation of the proximal, but not the distal stomach, with consequent alteration in the intragastric distribution of contents and antral overload. Evidence for a relationship between symptom subgroups and different pathophysiologic and psychopathologic mechanisms continues to increase,15Fischler B. Tack J. de Gucht V. et al.Heterogeneity of symptom pattern, psychosocial factors, and pathophysiological mechanisms in severe functional dyspepsia.Gastroenterology. 2003; 124: 903-910Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar although this aspect remains controversial16Boeckxstaens G.E. Hirsch D.P. Kuiken S.D. et al.The proximal stomach and postprandial symptoms in functional dyspeptics.Am J Gastroenterol. 2002; 97: 40-48Crossref PubMed Google Scholar, 17Bredenoord A.J. Chial H.J. Camilleri M. et al.Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms.Clin Gastroenterol Hepatol. 2003; 1: 264-272Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar, 18Delgado-Aros S. Camilleri M. Cremonini F. et al.Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia.Gastroenterology. 2004; 127: 1685-1694Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar and is likely influenced by studies of different patient populations. Gastric hyporeflexia may be a factor in the reduced tolerance of FD patients to intragastric volume increase, thereby contributing to the generation of clinical symptoms in the absence of major motor dysfunction.14Caldarella M.P. Azpiroz F. Malagelada J.-R. Antro-fundic dysfunctions in functional dyspepsia.Gastroenterology. 2003; 124: 1220-1229Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar In irritable bowel syndrome (IBS), hypersensitivity to rectal or sigmoid balloon distention can be shown in 50% to 70% of patients. As well, at least half of patients perceive the stimuli over wider referral areas than healthy subjects, and the proportion of patients reported as hypersensitive thus depends, among other factors, on whether such abnormal viscerosomatic referral is included. In IBS patients without concomitant FD, rectal hypersensitivity appears to be present in isolation, whereas if FD is also present, gastric, as well as rectal, hypersensitivity is often demonstrable.11Bouin M. Lupien F. Riberdy M. et al.Intolerance to visceral distention in functional dyspepsia or irritable bowel syndrome an organ-specific defect or a pan-intestinal dysregulation?.Neurogastroenterol Motil. 2004; 16: 311-314Crossref PubMed Scopus (70) Google Scholar Cerebral responses to rectal balloon distention appear to be abnormal in IBS, supporting the concept of visceral hypersensitivity. Although there is diversity in the literature, the largest brain-imaging studies suggest that IBS patients show augmented activation in the dorsal portion of the anterior cingulate cortex, in association with increased subjective pain reports to the stimuli.9Naliboff B.D. Derbyshire S.W.G. Munakata J. et al.Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation.Psychosom Med. 2001; 63: 365-375PubMed Google Scholar, 19Mertz H. Morgan V. Tanner G. et al.Regional cerebral activation in irritable bowel syndrome and control subjects with painful and non-painful rectal distention.Gastroenterology. 2000; 118: 842-848Abstract Full Text Full Text PDF PubMed Scopus (536) Google Scholar, 20Verne G. Himes N. Robinson M. et al.Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome.Pain. 2003; 103: 99-110Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar These data do not necessarily indicate a cerebral etiology for visceral hypersensitivity; they could in fact reflect a normal cerebral response to a heightened incoming sensory signal. However, brain areas important in descending pain inhibition, namely the perigenual anterior cingulate cortex and the periaqueductal gray region of the brainstem, appear to be underactive in IBS,9Naliboff B.D. Derbyshire S.W.G. Munakata J. et al.Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation.Psychosom Med. 2001; 63: 365-375PubMed Google Scholar, 21Silverman D.H.S. Munakata J.A. Ennes H. et al.Regional cerebral activity in normal and pathological perception of visceral pain.Gastroenterology. 1997; 112: 64-72Abstract Full Text PDF PubMed Scopus (501) Google Scholar and further studies are required. Both rectal and small bowel hypersensitivity in IBS have been associated with motor hyperreactivity in response to gut stimuli.22Whitehead W.E. Holtkotter B. Enck P. et al.Tolerance for rectosigmoid distention in irritable bowel syndrome.Gastroenterology. 1990; 98: 1187-1192Abstract Full Text PDF PubMed Scopus (589) Google Scholar, 23Evans P.R. Bennett E.J. Bak Y.-T. et al.Jejunal sensorimotor dysfunction in irritable bowel syndrome—Clinical and psychosocial features.Gastroenterology. 1996; 110: 393-404Abstract Full Text PDF PubMed Scopus (57) Google Scholar Alterations in the colonic motor24Snape W.J. Carlson G.M. Cohen S. Colonic myoelectric activity in the irritable bowel syndrome.Gastroenterology. 1976; 70: 326-330Abstract Full Text PDF PubMed Scopus (179) Google Scholar, 25Clemens C.H. Samsom M. Roelofs J.M. et al.Association between pain episodes and high amplitude propagated pressure waves in patients with irritable bowel syndrome.Am J Gastroenterol. 2003; 98: 1838-1843Crossref PubMed Scopus (35) Google Scholar and sensory26Simren M. Abrahamsson H. Bjornsson E.S. An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome.Gut. 2001; 48: 20-27Crossref PubMed Scopus (183) Google Scholar response to feeding have been documented. A temporal correlation between high-amplitude propagating contractions and abdominal pain episodes has been observed in the ileocecal region27Kellow J.E. Phillips S.F. Miller L.J. et al.Dysmotility of the small intestine in irritable bowel syndrome.Gut. 1988; 29: 1236-1243Crossref PubMed Scopus (224) Google Scholar and sigmoid colon25Clemens C.H. Samsom M. Roelofs J.M. et al.Association between pain episodes and high amplitude propagated pressure waves in patients with irritable bowel syndrome.Am J Gastroenterol. 2003; 98: 1838-1843Crossref PubMed Scopus (35) Google Scholar in IBS patients. However, these high-amplitude contractions were also observed in the absence of pain in IBS patients and did not differ manometrically from those associated with pain. Moreover, only a proportion of the IBS patients in these studies showed such contractions. The colorectal tonic reflex, namely the normal increase in rectal tone in response to distention of the descending colon, has been reported to be attenuated in IBS patients.28Ng C. Danta M. Kellow J. et al.Attenuation of the colorectal tonic reflex in female patients with irritable bowel syndrome.Am J Physiol. 2005; 289: G489-G494Google Scholar Recent studies evaluating intestinal gas dynamics further substantiate the role of combined sensory and motor disturbances in symptom production. Gas-transit studies have revealed that patients with bloating exhibit impaired reflex control of gut handling of contents.29Serra J. Salvioli B. Azpiroz F. et al.Lipid-induced intestinal gas retention in the irritable bowel syndrome.Gastroenterology. 2002; 123: 700-706Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 30Passos M.C. Tremolaterra F. Serra J. et al.Impaired reflex control of intestinal gas transit in patients with abdominal bloating.Gut. 2005; 54: 344-348Crossref PubMed Scopus (80) Google Scholar Segmental pooling, either of gas or alternatively of solid/liquid components, may induce the sensation of bloating, particularly in patients with hypersensitivity. Furthermore, altered viscerosomatic reflexes may contribute to abdominal wall protrusion and objective distention, even without major intra-abdominal volume increment. Several potential causes of the sensorimotor dysfunction in the FGID have been identified. The most important of these are discussed briefly. There is now a body of evidence that documents various genetic alterations in both FD31Holtmann G. Siffert W. Haag S. et al.G-protein B3 825 CC genotype is associated with unexplained (functional) dyspepsia.Gastroenterology. 2004; 126: 971-979Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar and IBS.32Gonsalkorale W.M. Perrey C. Pravica V. et al.Interleukin 10 genotypes in irritable bowel syndrome; evidence for an inflammatory component.Gut. 2003; 52: 91-93Crossref PubMed Scopus (234) Google Scholar The importance of early-life experiences and social learning in the etiopathogenesis of the FGIDs is also increasingly recognized. These 2 areas are reviewed in accompanying articles. Also of note in IBS are reported alterations in the synthesis, uptake, and turnover of secreted serotonin in the gut mucosa.33Coates M.D. Mahoney C.R. Linden D.R. et al.Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.Gastroenterology. 2004; 126: 1657-1664Abstract Full Text Full Text PDF PubMed Scopus (671) Google Scholar, 34Dunlop S.P. Coleman N.S. Blackshaw E. et al.Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.Clin Gastroenterol Hepatol. 2005; 3: 349-357Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar Given the role of mucosal serotonin in intestinal motility and possibly sensation, it is conceivable that such alterations contribute to sensorimotor dysfunction in IBS, but further work is required. The entity of postinfectious IBS is well recognized, with a prevalence of up to 30% after an acute episode of bacterial gastroenteritis.35Neal K.R. Hebdon J. Spiller R. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome.Br Med J. 1997; 314: 779-782Crossref PubMed Scopus (535) Google Scholar, 36Gwee K.-A