The pathogenesis of symptoms in irritable bowel syndrome (IBS) is multifactorial and varies from patient to patient. Disturbances of motor function in the small intestine and colon and smooth-muscle dysfunction in other gut and extraintestinal regions are prominent. Abnormalities of sensory function in visceral and somatic structures are detected in most patients with IBS, which may relate to peripheral sensitization or altered central nervous system processing of afferent information. Contributions from psychosocial disturbances are observed in patients from tertiary centers and primary practice. Proof of causation of symptom genesis for most of these factors is limited.
Although much research over the past decade has focused on pathogenic roles of inflammation or altered enteric microbiota in irritable bowel syndrome (IBS), an enormous body of literature published beginning in the 1940s has extensively characterized traditional factors believed to be involved in the genesis of symptoms, including motor, sensory, central nervous system (CNS), and psychological abnormalities. More recent investigations using modern methods and studying IBS subsets well defined by validated clinical surveys have provided more detailed delineation of peripheral sensorimotor and central factors in relation to dominant symptom profiles. Because IBS is a heterogeneous disorder, it is likely that these distinct traditional factors participate to varying degrees in different patients. Furthermore, it is probable that many of the novel pathogenic inflammatory or infectious factors currently being studied also elicit symptoms by influencing gut motor and sensory function or information processing in the CNS.
Motor dysfunction
Disturbances of motor activity in several gastrointestinal and extraintestinal sites have been characterized in the different IBS subtypes; however, their roles in symptom pathogenesis for the most part are unproved. Several mediators have been proposed to contribute to motor dysfunction in IBS.
Small Intestinal Motor Abnormalities
Small intestinal motor function frequently is disturbed in IBS; however, the relevance of these defects to symptom induction is unproved. Small intestinal transit is generally reported as delayed in patients with constipation-predominant IBS (C-IBS) and accelerated in patients with diarrhea-predominant (D-IBS), although some large studies have not observed this association. On magnetic resonance imaging (MRI), orocecal transit is accelerated in D-IBS, with associated reductions in terminal ileal diameter, possibly reflecting increased intestinal tone. Likewise, ileocolonic transit measured scintigraphically is accelerated postprandially in D-IBS.
Abnormalities of phasic small bowel contractile activity have been characterized in different subtypes of IBS. During fasting, a stereotypic pattern known as the migrating motor complex (MMC) cycles every 90 to 120 minutes to clear the proximal gut of undigested food residue. After consuming a caloric meal, small bowel motility converts to a fed pattern characterized by irregular phasic contractions that persist for up to 4 hours. Decreases in MMC amplitude and prolonged periodicity in patients with C-IBS and reductions in MMC cycle length in D-IBS have been reported. MMC propagation velocities reportedly are accelerated in IBS. Exaggerated jejunal fed responses, including increases in postprandial contractile frequencies, are seen in some patients with IBS although some studies have observed reduced fed amplitudes in C-IBS. In both subtypes, the duration of the fed pattern is shorter than in healthy controls. Retrograde duodenal and jejunal contractions are prominent in many patients with IBS, especially postprandially, and are reported to correlate with diarrhea in some cases. Discrete clustered contractions consisting of bursts of phasic contractions occurring every minute in the duodenum or jejunum, and prolonged propagated contractions consisting of intense ileal complexes that evacuate the ileum, may occur more commonly in patients with IBS than in healthy volunteers. In some individuals, clustered contractions and prolonged propagated small intestinal contractions are associated with symptom exacerbations. However, such clusters also are observed in other gut motor disorders such as chronic intestinal pseudoobstruction (CIP) and in healthy individuals, indicating that these patterns are not specific for IBS. The report of small bowel myenteric neuronal damage in individuals with severe IBS raises the possibility that some cases may fall along a spectrum that includes conditions with greater morbidity such as CIP. Small intestinal phasic contractile responses to other stimuli also may be modified in IBS. Cholecystokinin evokes high-amplitude ileal contractions in patients with D-IBS, whereas neostigmine induces discrete clustered contractions in both IBS subtypes. Conversely, reductions in duodenal motor responses to colonic distention are blunted in IBS.
Colonic Motor Abnormalities
Colonic motor abnormalities are prevalent in IBS, but correlate imperfectly with symptomatic bowel disturbances. In general, colon transit is accelerated in D-IBS and delayed in C-IBS. However, recent surveys observed abnormal colon transit in only 30% and 32% of patients with functional gastrointestinal disorders. Symptoms correlating with colonic transit in IBS include abnormalities of stool form, frequency, and ease of passage.
IBS has been associated with altered colonic myoelectric activity as well as phasic and tonic contractile function. In contrast to the stomach and small intestine, the colon shows no dominant myoelectric pacemaker activity. Rather, short spike bursts of 5 to 15 seconds underlie short-duration mixing contractions, whereas long spike bursts 15 to 60 seconds in duration are associated with contractions that show some propulsive characteristics. Early investigations observing abnormal 3-cycle-per-minute myoelectric rhythms in IBS were not confirmed by subsequent studies; such dysrhythmias instead were attributed to psychiatric factors in affected patients. High-amplitude propagated contractions (HAPCs) occurring infrequently throughout the day produce propulsive mass fecal movements, including those that precede defecation. In some older studies, no differences in phasic colonic motility were observed between patients with IBS and healthy controls. However, using wireless motility capsules, increases in colonic contractile activity were noted in C-IBS compared with healthy controls that are greater in the latter phases of colonic transit ( Fig. 1 ). Other recent investigations observe that patients with D-IBS have more frequent HAPCs versus healthy volunteers, whereas patients with C-IBS show fewer such complexes. In 1 investigation, 90% of HAPCs were associated with painful episodes. Others also have correlated HAPCs with pain reports. In normal volunteers, meal ingestion evokes increased myoelectric and motor activity, known as the gastrocolonic response, which peaks 20 to 30 minutes after eating. Patients with IBS may show exaggerated gastrocolonic responses lasting up to 3 hours, especially after high-fat meals. Rectal compliance has been reported to be reduced in some but not all studies in IBS. Colon tone in IBS measured by barostat methods is increased at baseline, is either unaffected or reduced after meal ingestion, and is blunted in response to colonic distention. One recent study observed a caloric dependence to abnormal tonic responses to meals in D-IBS, with reduced tone with 250-kcal meals and normalization of the response after consuming 1000 kcal of nutrients. As in the small bowel, IBS is associated with exaggerated colon motor responsiveness to exogenous stimulation, including abnormally prolonged and intense colonic contractions after colorectal balloon inflation, cholinergic stimulation, cholecystokinin administration, and colonic perfusion of deoxycholic acid. Recent investigations suggest evidence of dyssynergic defecation in some C-IBS cases, with affected patients having prolonged balloon expulsion times. This finding raises the possibility that many of the distal gut symptomatic and functional disturbances in IBS may relate to anorectal outlet dysfunction rather than colon wall abnormalities.
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