UMLS:C0022104 - FACTA Search

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Query: UMLS:C0022104 (irritable bowel syndrome)
8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychological stress is widely believed to play a major role in functional gastrointestinal (GI) disorders, especially irritable bowel syndrome (IBS), by precipitating exacerbation of symptoms. The available data clearly demonstrate that inhibition of gastric emptying and stimulation of colonic transit is the most consistent pattern in the motility response of the GI tract to acute or short-term stress. Thus, one might propose that these alterations might play a pathophysiological role in dyspeptic symptoms and alterations in stool frequency and consistency in patients with stress-related functional GI disorders. Taken together, the above-mentioned studies suggest that the colonic motor response to stress is exaggerated in IBS. There is evidence that an increased emotional response is associated with this difference in colonic, and perhaps also gastric motor responses to certain stressors. However, almost no valid data are available so far from human studies addressing the question if differences in motility responses to stress between patients with functional GI disorders and healthy subjects are due to an altered stress response associated with an imbalance of the autonomic nervous system or increased stress susceptibility. We can summarize that in experimental animals the most consistent pattern of GI motor alterations induced by various psychological and physical stressors is that of delaying gastric emptying and accelerating colonic transit. Endogenous corticotropin-releasing factor (CRF) in the brain plays a significant role in the central nervous system mediation of stress-induced inhibition of upper GI and stimulation of lower GI motor function through activation of brain CRF receptors. The inhibition of gastric emptying by CRF may be mediated by interaction with the CRF-2 receptor, while CRF-1 receptors are involved in the colonic and anxiogenic responses to stress. Endogenous serotonin, peripherally released in response to stress, seems to be involved in stress- and central CRF-induced stimulation of colonic motility by acting on 5HT-3 receptors. Taken together, the limited data available from investigations in healthy subjects and patients with functional GI disorders provide some evidence that stress affects visceral sensitivity in humans. Acute psychological stress seems to facilitate increased sensitivity to experimental visceral stimuli, if the stressor induces a significant emotional change. In summary, studies in experimental animals suggest that stress-induced visceral hypersensitivity is centrally mediated by endogenous CRF and involvement of structures of the emotional motor system, e.g. the amygdala. Stress-induced activation or sensitization of mucosal mast cells in the GI tract seem to be involved in stress-associated alterations of visceral sensitivity.
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PMID:Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivity. 1175 38

The evaluation of a group of polyamine analogs as agents to ameliorate diarrhea-predominant irritable bowel syndrome is described. Each compound was assessed when administered subcutaneously in a psychological stress-induced model of irritable bowel syndrome in rodents for its ability to reduce stool output in a dose-dependent manner. The spermine pharmacophore is shown to be an excellent platform from which to construct compounds to treat irritable bowel syndrome. The activity of the compounds is very dependent on both the nature of the terminal alkyl groups and the geometry of the methylene spacers separating the nitrogens. In addition to the subcutaneous studies, several compounds, N1,N11-diethylnorspermine, N1,N12-diethylspermine, N1,N12-diisopropylspermine, N1,N14-diethylhomospermine, N,N'-bis[5-(ethylamino)pentyl]-1,4-butanediamine, N,N'-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane, and N,N'-bis[3-(ethylamino)propyl]-trans-1,4-cyclohexanediamine, were subsequently evaluated for oral efficacy. The remarkable activity of N,N'-bis[3-(ethylamino)propyl]-trans-1,4-cyclohexanediamine underscores the need to explore this framework further as a pharmacophore for the construction of other analogues to relieve the symptoms of diarrhea-predominant IBS.
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PMID:Control of irritable bowel syndrome with polyamine analogs: a structure-activity study. 1176 50

This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome.
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PMID:Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. 1180 52

Approximately 697000 United States military personnel participated in the Persian Gulf War (PGW) between August 1990 and March 1991. By April 1997, over 25% of veterans reported chronic health complaints of underdetermined etiology. Gastrointestinal symptoms were among the most frequently reported symptoms including abdominal pain and diarrhea. The objectives of this study were (1). to determine if PGW veterans chronic abdominal pain and diarrhea exhibit visceral and cutaneous hypersensitivity, (2). to determine if these differences in pain sensitivity are significantly associated with psychological stress. A total of 12 veterans (ten males, two females) (39+/-9 years) who were deployed to the Persian Gulf were enrolled. Seven civilians without prior military experience (five males, two females) and five veterans (five males) who had previously been deployed for active combat were enrolled as controls (35+/-9 years). All 12 PGW veterans reported chronic abdominal pain and diarrhea (negative diagnostic workup) that developed during their tour of duty in the Persian Gulf region. All patients completed a battery of psychological assessments and then randomly received experimental visceral (rectal distension of 35 and 55 mmHg for 30s) and cutaneous (immersion of right foot in 45 and 47 degrees C water for 30s) pain stimuli after which they rated their pain intensity and pain unpleasantness on a continuous visual analogue scale (M-VAS) scale. The trials were repeated and the mean M-VAS scores for the two trials were recorded for each subject. In comparison to controls, PGW subjects reported statistically significant higher mean ratings of pain intensity and pain unpleasantness in response to 35 and 55 mmHg rectal distention (P<0.001) and in response to 45 and 47 degrees C water immersion (P<0.001) of the hand and foot. Results of the hierarchical regressions indicated that the psychological measures (i.e. anxiety, somatic focus) accounted for a significant amount of variance in each of the pain measures. PGW veterans who developed chronic abdominal pain and diarrhea during their tour of duty exhibit visceral hypersensitivity similar to patients with the irritable bowel syndrome. These veterans also have cutaneous hypersensitivity and higher levels of anxiety and somatic focus accounting for these differences in pain reporting.
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PMID:Visceral and cutaneous hypersensitivity in Persian Gulf war veterans with chronic gastrointestinal symptoms. 1262 May 99

Activation of serotonin 5-HT(4) receptors has been proposed as treatment for irritable bowel syndrome, a common, complex and distressing gastrointestinal disorder. Abnormal intestinal motility and sensitivity in irritable bowel syndrome patients can result in diarrhea, constipation, abdominal pain, bloating, headache and fatigue; these and other symptoms can lead to exacerbation of psychological stress, which may in turn induce further physiological abnormalities and patient discomfort. The serotonin agonist tegaserod binds with high affinity to 5-HT(4) receptors and has demonstrated potent pharmacological effects on the mid- and distal gut. Tegaserod has been safely employed in clinical trials where it has demonstrated efficacy in normalizing intestinal function, thereby improving irritable bowel syndrome symptoms.
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PMID:Tegaserod: a serotonin 5-HT4 receptor agonist for treatment of constipation-predominant irritable bowel syndrome. 1564 12

Irritable bowel syndrome (IBS) is a debilitating disease, which is characterised by recurrent abdominal cramping and pain, and is associated with either constipation and/or diarrhoea. It is approximately twice as prevalent in women as it is in men and is among the most common gastrointestinal (GI) disorders encountered in primary care. The aetiology of the disease is poorly understood but may include motility dysregulation, visceral sensitivity, inflammation, bacterial infection, dietary antigens, psychological stress, GI surgery or a gut-brain phenomenon. At present, there is no acceptable treatment for IBS, although recent advances indicate that some relief may be achieved by the administration of compounds that act on 5-HT (serotonin) receptors. This suggestion is the result of numerous studies which have shown that 5-HT may exert a number of diverse effects on human GI tissues. In addition, it has emerged that the levels of the 5-HT metabolite (5-HIAA) are raised in the plasma of IBS patients and that administration of 5-HT-like compounds may mimic the symptoms of IBS. It has therefore been proposed that therapy with compounds that act at 5-HT receptors will return the intestine to normal activity and alleviate the pain experienced by these patients. One compound (alosetron, a 5-HT3 receptor antagonist) has already been released onto the market but showed benefit in female patients only and only in those whose primary symptom was diarrhoea. In addition, the compound was recently withdrawn following concerns over its safety. The reasons why alosetron only appears to show efficacy in females, why these treatments are only effective in a subset of the population of IBS patients and why alosetron elicits its particular side effect profile have not been elucidated. One further serotonergic compound, tegaserod (Zelmac, a 5-HT4 receptor agonist), has shown promise for the treatment of patients with constipation-predominant IBS and is currently in pre-registration for this indication. It is clear, however, that further research will have to take place before the utility of serotonergic modulation in the treatment of IBS can be fully validated.
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PMID:Serotonergic modulation and irritable bowel syndrome. 1598 96

Irritable bowel syndrome (IBS) is presumed to be a gastrointestinal motility disorder with the brain-gut interaction. Psychological stress and stimuli of the colonic lumen increase colonic motor function which is exaggerated in IBS patients. Corticotropin-releasing hormone (CRH) is considered to be a major mediator of stress responses in the brain-gut interaction. Similarly, peripheral administration of CRH affects colonic motility, induces abdominal symptoms and stimulates ACTH secretion, all of which are exaggerated in IBS patients. CRH antagonist blocks the greater responses of colonic motility in IBS. CRH is a key peptide in the pathophysiology of IBS with the brain-gut interaction.
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PMID:[The gastrointestinal motor function in irritable bowel syndrome (IBS)]. 1689 9

Irritable bowel syndrome (IBS) is a disease of unclear, complex pathophysiology characterised by abdominal pain and discomfort and altered bowel activity. It affects an estimated 10-15% of individuals worldwide and has a large impact on quality of life (QOL) and both direct and indirect healthcare costs. Symptoms of IBS are usually triggered by disruption of gastrointestinal (GI) function secondary to infection, dietary factors, lifestyle changes or psychological stress. While most currently available pharmacological treatments of IBS focus on symptomatic treatment of the syndrome, agents that attempt to address the pathophysiology of the disease, in particular the role of serotonin, have received much attention in recent years. However, there is growing concern that serotonergic agents as a class may be associated with rare, but serious, episodes of ischaemic colitis, with several cases of this complication having been reported in association with use of serotonergic agents that have reached the market. Thus, there remains an important need for safe and effective agents that treat the symptoms of IBS. Otilonium bromide, a spasmolytic agent, has been widely used worldwide and has been found to be effective and safe for managing abdominal pain. Clinical trials indicate that it improves baseline abdominal pain and distension, and is particularly effective in reducing diarrhoea. Combining otilonium bromide with benzodiazepines, such as diazepam, may improve the efficacy of the agent with respect to GI symptoms, while also treating underlying anxiety disorders. More research is required to confirm the efficacy and mechanisms of action associated with this combination therapy in IBS. Safety data from clinical trials and postmarketing sources indicate that otilonium bromide is well tolerated, with a safety profile comparable to placebo in clinical trials and only two reported cases of adverse reactions (urticaria) among 10-year postmarketing data. This article reviews the pathophysiology and treatment of IBS with a particular focus on the role of otilonium bromide in the management of this condition.
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PMID:Irritable bowel syndrome. 1717 77

Psychological stress experienced in early life plays an important role in the development of visceral hyperalgesia in irritable bowel syndrome (IBS). Neonatal maternal separation has been shown to trigger a long-term alternation in stress-induced responses to visceral nociceptive stimuli in rats. The aim of the present study was to show a direct evidence of stress-induced alteration in central neuronal responses to colorectal distention (CRD) in rats by a quantitative study of c-fos expression in relevant brain structures. Male Wistar rat pups were subjected to 180-min daily neonatal maternal separation (NMS) for 13 consecutive days (from PND 2 to PND 14). The expression of c-fos was examined by using immunohistochemistry. Increased c-fos expression was observed, for the first time, in the cingulate cortex (3-fold) in NMS rats in comparison with the control group at basal condition. At noxious CRD (80 mm Hg), c-fos expression was induced in the supraspinal centers and in both the superficial (laminae I-II) and the deeper laminae (laminae V-VI and X) of the spinal cord in rats. Significantly more Fos-IR nuclei were found in the laminae I and II, and laminae V-VI of the lumbarsacral spinal cord, the paraventricular thalamic nucleus, the cingulate cortex, the amygdaloid central nucleus in NMS rats, but not in the solitary tract, the central medial thalamic nucleus, the ventromedial hypothalamic nucleus, and the periaquaductal gray. The present results indicate that NMS has sensitized the cingulate cortex and upregulated the activity of the ascending pathway at spinal level as well as the thalamo-cortico-amydala pathway to CRD. The upregulation and sensitization of these pathways may be responsible for the development of visceral hypersensitivity in IBS.
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PMID:Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat. 1743 64

Irritable bowel syndrome (IBS) is a ubiquitous but heterogeneous syndrome characterized by abdominal pain and erratic bowel habits that affects 5% to 10% of the population. Although current definitions specify that there are no structural or biochemical abnormalities to account for the symptoms, there is growing evidence that in at least a subset of IBS patients, there is low-grade inflammation characterized by increased T lymphocytes and mast cells. Whether this is cause or effect is uncertain, as there is also clear evidence of bidirectional communication between the immune and nervous systems, and at least some of the mucosal changes could be secondary to psychological stress. A small percentage (6%-17%) of patients develop IBS symptoms for the first time after an acute episode of infective gastroenteritis (postinfective IBS), which appears to be directly responsible for low-grade immune activation. However, even in this group, preexisting psychological factors are as important as mucosal ones. Specific anti-inflammatory treatments have not been systematically evaluated, but there is no evidence of benefit currently.
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PMID:Irritable bowel syndrome: bacteria and inflammation--clinical relevance now. 1776 Nov 24

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