Motor function in irritable bowel syndrome

MOTOR DYSFUNCTION IS IMPLICIT IN THE DEFINITION OF IBS According to the ‘Rome criteria’, IBS is defined as “a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit, with features of disordered defecation and distention” (1). The change in bowel habit implies that IBS is a disorder of motility. An obvious deficiency in the Rome definition of IBS is the absence of symptoms such as urgency and abdominal pain, or diarrhea in the postprandial period, which also implies a motor disturbance. Several studies, including the classical one by Chaudhary and Truelove (2), have shown that a prominent gastrocolonic response to feeding is characteristic of a subgroup of patients, and that this response can be assessed subjectively and objectively with colonic manometry.

Patients with functional diarrhea associated with postprandial urgency and borborygmi, and a sense of incomplete rectal evacuation are regarded by many clinicians as suffering from a variant of IBS, despite the absence of abdominal pain, and are not identified according to the Rome criteria.

WHAT MECHANISMS LEAD TO IBS? ROLE OF ABNORMAL MOTOR FUNCTION
IBS is a biopsychosocial disorder in which altered motility or sensation in the small bowel or colon is modulated by input from the central nervous system, including the higher centres (Figure 1).Table 1 summarizes the pathophysiological mechanisms that lead to or aggravate IBS.Importantly, these individual mechanisms are not mutually exclusive.Thus, although some dysfunction may predominate, more than one may be operating in any individual.Understanding these mechanisms and identifying which ones pertain to an individual patient provide a basis for optimizing the management of IBS.
The abnormal motor functions of the digestive tract in IBS have been recognized for several decades (3)(4)(5)(6).More recently, markers of altered motor function have been described during small bowel motility studies in patients with IBS.Horowitz and Farrar (7) were the first to observe clustered contractions during episodes of abdominal colic.Kellow and Phillips (8) confirmed this finding and identified the coincidence of painful cramps with the passage of high amplitude pressure waves through the ileocecal region, suggesting that altered sensation is an important cofactor of the clustered activity.Gorard et al (9) showed no increased frequency of clusters in patients with IBS with diarrhea compared with healthy people.Patients with diarrhea-predominant IBS have more jejunal contractions during phase II and postprandially than healthy subjects.The colons of patients with diarrhea-predominant IBS have a greater number of fast contractions (10) and propagated contractions (11).Functional diarrhea is associated with normal colonic tone and increased postprandial high amplitude propagated contractions (12).In contrast, patients with constipationpredominant IBS have fewer high amplitude propagated contractions (13).
Cann and colleagues (14) showed that patients with IBS and diarrhea had accelerated whole gut transit times; in some patients, fast orocecal transit was also observed.Vassallo et al (15) showed that transit through the ascending and transverse colon is accelerated in patients with diarrhea-predominant IBS.This rapid transit through the proximal colon is positively correlated with stool weight (15).Conversely, patients with idiopathic constipation, normal colonic diameter, and normal anorectal and pelvic floor function have overall delays in colonic transit, with predominant slowing of proximal colonic emptying (16,17).
The increased sensitivity of the anorectum is accompanied by the development of excessive reflex motor activity in the rectum (18).These observations suggest that there are interactions between excessive sensation and motor responsiveness.Interestingly, increased rectal sensitivity is exclu-sive to patients with diarrhea-or urgency-predominant IBS (18,19).Thus, increased anorectal sensitivity may explain the symptoms of pain before bowel movements and a sense of incomplete evacuation, while the increased motor response to these stimuli may result in the increased frequency of bowel movements, often unassociated with increased stool weight in patients with IBS.The level of rectal compliance and tone also influences rectal sensitivity during mechanical stimulation (20).

LUMINAL FACTORS IRRITATING THE INTESTINE MAY ALTER ITS
SECRETOMOTOR FUNCTION There are several situations in which factors present in the intestinal lumen may alter intestinal function, causing an irritated gut (21).These luminal factors probably aggravate the underlying IBS rather than being an intrinsic component of the syndrome, and include exogenous dietary components and possibly endogenous chemicals involved in the digestive process.Malabsorbed sugars and food allergens may be important in IBS.Experimentally, luminal antigenic challenge in the sensitized rat intestine induces prominent contractile activity and diarrhea (22).
Can J Gastroenterol Vol 13 Suppl A March 1999 9A Motor function in IBD The ileum of patients with IBS is excessively sensitive to the secretory effects of perfused bile acids (23).Bile acid malabsorption may be underdiagnosed (24).Short or medium chain fatty acids, which may reach the right colon in patients with borderline absorptive capacity or rapid transit in the small bowel, induce rapidly propagated, high pressure waves in the right colon.These waves propel colonic content extremely effectively and may result in pain or diarrhea (25,26).

INITIAL TREATMENT OF IBS
Figure 2 provides a management algorithm for IBS (27).If no specific dietary intolerance is identified, diarrhea in IBS patients should be treated symptomatically with antidiarrheals such as diphenoxylate or loperamide (28).Tricyclic antidepressants, such as desipramine 50 mg tid or amitriptyline 10 to 25 mg bid, significantly relieve diarrhea and associated pain; these effects appear to be at least partly due to the anticholinergic actions of the tricyclic antidepressents (29).Calcium channel blockers (such as verapamil 40 mg bid) may be used as a secondary treatment (30).Constipation and osmotic agents, and moderate fibre supplementation are first-line measures, and laxatives or prokinetics are second-line measures.

THERAPY DIRECTED AT ABNORMAL MOTILITY IN IBS
Table 2 summarizes the literature on the effectiveness of smooth muscle relaxant medications (31).These data are based on results from published articles of randomized, double-blind, placebo controlled studies of at least two weeks' duration.The mean response for abdominal pain was 68% (range 23% to 87%) for active medication and 31% (range 22% to 66%) for placebo.Similarly, for global assessment, mean responses to drug and placebo were 73% (range 39% to 89%) and 41% (range 13% to 69%), respectively.A metaanalysis by Poynard et al (32) indicated that some of these agents, such as mebeverine, octylonium and cimetropium, are worthy of trial.Several novel approaches (Table 3) are also in the process of thorough evaluation in phase II or phase III trials, such as the kappa opioid agonist fedotozine,

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Can J Gastroenterol Vol 13 Suppl A March 1999 and 5-hydroxytryptamine 3 and 5-hydroxytryptamine 4 antagonists (33,34).Alternative therapeutic strategies for patients with significant pain are hypnotherapy or psychotherapy, but their effects on motor function have not been explained.

CONCLUSIONS
Data from clinical observations, and physiological and pharmacological studies support the concept that abnormal motor function is an important primary or secondary component of IBS.
Can J Gastroenterol Vol 13 Suppl A March 1999 11A Motor function in IBD

TABLE 2 Efficacy of anticholinergics and antispasmodics in the treatment of irritable bowel syndrome Abdominal pain Overall assessment Design n
PG Parallel group; XO CrossoverFigure 2) Algorithm detailing a practical approach to management of irritable bowel syndrome.Ba Barium; ELEC Electrolytes; ESR Erythrocyte sedimentation rate; Flex Flexible; O Ova; OSM Osmolality; P Parasites; SB Small bowel; TSH Thyroid-stimulating hormone; yr Year.Reproduced with permission from reference 31 and adapted from a similar algorithm in reference 27