Functional Gastrointestinal Disorders: Novel Insights and Treatments

, Mayo Clinic and Mayo Foundation, Rochester, Minn.

Disclosures

Medscape General Medicine. 1999;1(3) 

In This Article

Functional Dyspepsia

Pathogenesis and Clinical Presentation

Functional dyspepsia is also a biopsychosocial disorder; disturbances in psychosocial function, altered motility, and altered sensation interact to induce the condition.[47] Whereas much time and effort has been spent exploring the role of infectious organisms such as Helicobacter pylori in the context of nonulcer dyspepsia over the past decade,[48,49] it is now clear from eradication and outcome studies that, in the vast majority of individuals, the organism is probably an "innocent bystander" in the absence of ulceration. Depending on how the disorder is defined in different epidemiologic studies, the prevalence of functional dyspepsia ranges from 5% to 25%.[12] As with IBS, this functional disorder results in considerable disturbance in quality of life, social function, and healthcare utilization.[15]

Among adults with nonulcer dyspepsia, approximately 30% have impaired gastric emptying of solids[50,51,52,53]; these patients respond to prokinetic medications.[53] A second major motor abnormality associated with this disorder is impaired postprandial gastric accommodation (Figure 6), which results in early satiety and weight loss.[54]

Figure 6. Measurement of gastric accommodation response with an intragastric, barostatically controlled balloon. Note greater increase in volume (suggesting greater gastric accommodation) in healthy control compared with 2 patients with functional (nonulcer) dyspepsia. Adapted from Thumshirn et al. [62]

The other major pathophysiologic disturbance of functional dyspepsia is gastric hypersensitivity.[55,56,57] In this setting, although the elastic properties (compliance) of the stomach are unimpaired,[55,56,57] patients experience pain or discomfort at lower thresholds. Thus, the visceral afferents are considered hypersensitive. Dyspeptic patients also have evidence of hyperalgesia, because the same stimulus produces higher pain scores in this population than in healthy volunteers.[57]

Treatment

Several studies performed in recent years have noted a lack of gastric accommodation in association with hypersensitivity during the fasting or postprandial periods.[54,57] This lack of accommodation may suggest that a pharmacologic relaxation of the stomach would improve the dyspeptic symptoms in these patients. Relatively simple tests[58,59,60] -- such as a water-load or nutrient drink test -- can assess the degree of accommodation and hypersensitivity. However, only 50% of dyspeptic patients demonstrate hypersensitivity by these noninvasive methods.[59,60]

Pharmacologically induced relaxation of the stomach alone may not necessarily reduce postprandial pain. Studies involving the inflation of an intragastric balloon at different pressures, such as the study by Tack and colleagues,[61] have shown that while cisapride results in increased accommodation of the stomach, it lowers (rather than raises) the threshold pressures for the induction of discomfort. Similarly, the nitric oxide donor, nitroglycerin, results in marked, dose-related relaxation of the stomach but no change in pain sensation in response to balloon distention.[62] In fact, these patients experienced a worsening sensation of nausea. By contrast, clonidine, an alpha-2 adrenergic agonist with central antinociceptive action, was associated with a reduction in pain perception during gastric distention (without affecting accomodation or emptying); relaxation in gastric wall tension due to clonidine accounted for about 40% of the variance in pain sensation.[62] These data suggest that novel approaches to therapy for functional dyspepsia will require a visceral antinociceptive effect rather than an exclusive relaxatory action.

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