... SELECTED ABSTRACTS... The following abstracts, from medical journals containing literature on irritable bowel syndrome, were selected for their relevance to this supplement. A Technical Review for Practice Guideline Development in Irritable Bowel Syndrome A greater understanding of the pathophysiology of irritable bowel syndrome (IBS), as well as improved diagnostic precision and the development of specific treatments, has facilitated a practical approach to diagnosis and management of patients with this disorder. This critical review of the existing literature addresses the epidemiology of IBS, its proposed pathophysiology, the role of psychosocial factors in symptom experience and behavior, the diagnostic approach, and recommendations for therapy. IBS is now believed to result from dysregulation of intestinal motor, sensory, and central nervous system function. Disturbances in intestinal motility and enhanced visceral sensitivity lead to the symptoms of the disorder. Psychosocial factors have an important role in modulating the illness experience and its clinical outcome. Diagnostic precision has been increased with the use of multinational symptom-based criteria. Treatment involves an integrated pharmacologic and behavioral approach that is dictated by the needs of the patient and the severity of symptoms, taking into account both their physiological and psychosocial contributions. This literature review and the recommendations presented were prepared for the American Gastroenterological Association Patient Care Committee. Drossman DA, Whitehead WE, Camilleri M. Irritable bowel syndrome: A technical review for practice guideline development. Gastroenterology 1997;112:2120-2137. Important Symptom Differences in Patients with Irritable Bowel Syndrome Likely Affect Treatment Responses Patients with irritable bowel syndrome (IBS) are commonly subclassified into 2 groups based on predominant bowel habits, which may be related to different patterns of autonomic outflow to the intestinal tract. It appears there are notable differences in self-reported symptoms between these subgroups, which are likely to influence response to certain treatments. This investigation examined whether patients with different bowel habit predominance differed in self-reported viscerosensory symptoms related to the upper and lower gastrointestinal tract, somatosensory symptoms, and constitutional functions. Compared with patients who experienced diarrhea-predominant symptoms, patients with constipationpredominant symptoms were more often female. Symptoms referred to the upper gastrointestinal tract were also reported more frequently in IBS patients with constipation, and this subgroup reported more lower gastrointestinal bloating and musculoskeletal symptoms, as well as greater impairment in sleep, appetite, and sexual function. Thus, IBS patients with constipation appear to have a greater vigilance toward visceral and somatic sensations whereas IBS patients with diarrhea showed primarily enhanced autonomic responses. These findings may be related to differences in autonomic or perceptual responses to visceral and somatic responses and are likely to have implications for treatment responses in the 2 subgroups. Schmulson M, Lee O-Y, Chang L, Baliboff B, Mayer EA. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol 1999;94:2929-2935. VOL. 7, NO. 8, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S279
... SELECTED ABSTRACTS... Symptoms Correlate with Perception Thresholds The diagnosis of irritable bowel syndrome (IBS) is based on symptom criteria because of the lack of specific and biological markers unique to the disorder. However, the possible physiological correlates of these criteria are not known. These investigators sought to examine whether there was a relationship between the currently used Rome symptom criteria and distinct alterations in visceral perception. One of the most reproducible findings in IBS patients is an enhanced sensitivity to rectosigmoid balloon distension. In this study, a decrease in rectal discomfort thresholds after sigmoid stimulation was seen in all IBS patients regardless of specific symptoms. However, baseline and postsigmoid stimulation thresholds were lower in IBS patients with constipation-related symptoms. The lowering of rectal discomfort thresholds after sigmoid stimulation was observed regardless of the presence or absence of any Rome criteria or symptom severity. The investigators speculate that the presence of pain associated with change in stool consistency, hard and/or lumpy stools, and the absence of loose and/or watery stools which point towards constipation, a Rome symptom criterion are related to visceral hypersensitivity and this symptom may be an important discriminant in classifying bowel habit predominance in IBS. Schmulson M, Lee O-Y, Chang L, Baliboff B, Mayer EA. Correlation of symptom criteria with perception thresholds during rectosigmoid distension in irritable bowel syndrome patients. Am J Gastroenterol 2000;95:152-156. Heightened Pain Sensitivity of the Brain-Gut Axis Is Suggested in Patients with Irritable Bowel Syndrome The hypersensitivity to visceral distending stimuli seen in patients with irritable bowel syndrome (IBS) is thought to be related to abnormal brain-gut communication. Indeed, results of a small central nervous system positron emission tomography (PET) imaging study during rectal distension have suggested specific central nervous system abnormalities in visceral pain processing in patients with IBS. In contrast, the findings of this study suggest a normal pattern of activation in patients with IBS, but a heightened pain sensitivity of the brain-gut axis. Using functional magnetic resonance imaging (fmri) to measure changes in regional cerebral activity during stimulation, these investigators found that IBS patients activate the anterior cingulate cortex (ACC), a critical central nervous system pain center, to a greater extent than controls in response to a painful rectal stimulus. This hyperreactivity of the ACC to visceral stimulation in IBS patients could explain the heightened pain sensitivity in addition to altered descending reflexes that stimulate gastrointestinal motility. Both PET and fmri studies have shown the correlation of reported pain intensity and activation of pain centers is absent. The investigators speculate this distorted coupling between afferent stimuli and verbal reports of pain could be a result of cognitive and emotional factors. Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distension. Gastroenterology 2000;118:842-848. S280 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2001
... SELECTED ABSTRACTS... Increased Pain Sensitivity May Be Related to Selective Attention and Disease Attribution Because it is a reproducible finding in patients with irritable bowel syndrome (IBS), rectal pain sensitivity is sometimes thought of as a biological marker for IBS. However, this critical review of the literature on pain thresholds in patients with IBS spanning 24 years suggests this view needs to be reevaluated in light of more recent evidence regarding psychological influences on perception. Many of these new findings do not appear to be explainable on the basis of hypothesized biological differences between patients with IBS and controls. The authors developed a hypothetical model that attempts to integrate the various psychosocial, physiological, and methodological variables believed to influence the threshold at which patients with IBS report pain from rectal distension. Based on this model, the authors theorize that increased pain sensitivity in patients with IBS may be a result of 2 related cognitive traits: selective attention to gastrointestinal sensations and disease attribution. It suggests that early childhood learning through the reinforcement and modeling of illness behavior by parents is a principal determinant of these 2 cognitive traits. These psychological factors appear to influence pain thresholds in this population, determining where on the continuum of intensity of sensation IBS patients begin to report pain. New insights into the etiology of IBS may be gained with the understanding of this role of psychological influences on pain perception and may lead to more effective treatments. Whitehead WE, Palsson OS. Is rectal pain sensitivity a biological marker for irritable bowel syndrome: Psychological influences on pain perception. Gastroenterology 1998; 115:1263-1271. Fedotozine Relieves Hypersensitivity to Colonic Distension Because visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome (IBS), the opioid κ receptors on afferent nerves have been proposed as a target for new treatments for the disorder. This study investigated the effects of fedotozine, a potent and selective κ agonist, on responses to colonic distension and colonic compliance in patients with IBS. Fedotozine has shown promising results in basic and clinical studies. It alters the function of digestive afferent nerve pathways in animal models and has clinically been shown to improve abdominal symptoms related to functional bowel disorders and alter the sensory thresholds elicited by gastric distension in healthy volunteers. In this study, fedotozine appeared to reverse the visceral hypersensitivity observed in IBS patients and increased thresholds of perception of colonic distension without affecting colonic compliance. This latter finding would suggest that fedotozine would not affect bowel habits and thus could be administered to patients with either constipation- or diarrhea-predominant IBS for pain relief. The clinical effect of fedotozine is thought to be related to its direct action on visceral sensory pathways. Delvaux M, Louvel D, Lagier E, Scherrer B, Abitbol J-L, Frexinos J. The κ agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome. Gastroenterology 1999;116:38-45. VOL. 7, NO. 8, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S281
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