Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392326 (discomfort)
 22,423 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lack of validated outcome measures is a key limitation for the evaluation of drug efficacy in the treatment of irritable bowel syndrome (IBS). In clinical trials with tegaserod, the Subject's Global Assessment (SGA) of Relief (a global measure that includes overall wellbeing, abdominal pain/discomfort, and bowel function) was used to identify responders. A total of 1680 patients with IBS with constipation were included in two clinical studies comparing tegaserod with placebo. The SGA of Relief was obtained weekly by a single, self-administered question with five possible answers. Responders for the SGA of Relief reported statistically significant (P<.001) and clinically relevant improvements in multiple IBS-related symptoms compared with nonresponders. Response was also associated with a significant improvement in quality of life. The SGA of Relief is reliable as a new outcome measure for assessing response to therapy in IBS patients and has demonstrated responsiveness and reproducibility.
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PMID:Subject's Global Assessment of Relief: an appropriate method to assess the impact of treatment on irritable bowel syndrome-related symptoms in clinical trials. 1276 7

Irritable bowel syndrome (IBS) is a common disorder with a worldwide distribution; it is characterized by abdominal pain and discomfort associated with an alteration of bowel function. The treatment approach for IBS depends on the patient's presenting symptoms at the time of diagnosis, and treatment is usually directed toward the predominant symptom. In this review we discuss the current approach to the treatment of IBS.
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PMID:New approaches to the medical treatment of irritable bowel syndrome. 1286 65

The Global Improvement Scale (GIS) assesses multiple irritable bowel syndrome (IBS) symptoms using a patient-defined 7-point Likert scale ranging from symptoms substantially worse to substantially improved. To evaluate the scale as an efficacy end point, data were collected from two 12-week randomized, double-blind, placebo-controlled studies of female nonconstipated IBS patients. GIS responders were defined as having substantial or moderate improvement in IBS symptoms. GIS responders had more days with satisfactory control of urgency, firmer stools, fewer stools per day, and fewer days with incomplete evacuation compared to nonresponders. Substantially more GIS responders (90% and 89% in studies 1 and 2, respectively) were satisfied or very satisfied with their treatment overall compared to nonresponders (13% and 11%) (r = 0.8 in both studies). GIS responders had greater satisfaction with medication relief of pain and discomfort and the time needed to return to usual activities. Favorable correlations between GIS and work and nonwork productivity losses were observed. Correlation of the GIS measure with IBS clinical end points establishes the validity of the GIS for measuring improvement in IBS symptoms. The GIS may be useful in assessing the efficacy of IBS interventions in future clinical trials.
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PMID:Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. 1287 Jul 89

Alosetron (Lotronex, GlaxoSmithKline) is a potent and selective 5-HT(3)-receptor antagonist approved by the FDA for the treatment of women with diarrhoea-predominant irritable bowel syndrome (IBS) in whom conventional therapy has failed. Studies involving healthy volunteers and IBS patients have demonstrated a beneficial effect of treatment with alosetron on global IBS symptoms, abdominal pain and discomfort, altered bowel function as well as improvement of quality of life (QOL). Data from animals studies suggest the involvement of 5-HT(3) receptors on intrinsic primary afferent neurons in the mediation of the effect of alosetron on gastrointestinal motility and secretion. While definitive proof of a visceroanalgesic action is not available, an additional central mechanism of action is suggested by findings obtained in animal models, as well as from human brain imaging studies. Alosetron shows a greater effectiveness in women, and the role of genetic factors underlying inter-individual differences in the response to alosetron is currently under investigation. The most frequent adverse event associated with the use of alosetron is constipation and in some rare cases, the development of colonic mucosal ischaemia. In the following review, the most recent reported effects of alosetron on gastrointestinal motility, visceral sensitivity and anxiety, both in terms of preclinical and clinical data will be discussed. The impact of alosetron on QOL in IBS patients and the safety of treatment with alosetron, will also be covered.
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PMID:Alosetron and irritable bowel syndrome. 1459 62

From a historical perspective to the present day, all the evidence suggests that activation of cannabinoid receptors (CBRs) is beneficial for gut discomfort and pain, which are symptoms related to dysmotility and visceral perception. CBRs comprise G-protein coupled receptors that are predominantly in enteric and central neurones (CB1R) and immune cells (CB2R). In the last decade, evidence obtained from the use of selective agonists and inverse agonists/antagonists indicates that manipulation of CB1R can alter (1) sensory processing from the gut, (2) brain integration of brain-gut axis, (3) extrinsic control of the gut and (4) intrinsic control by the enteric nervous system. The extent to which activation of CB1R is most critical at these different levels is related to the region of the GI tract. The upper GI tract is strongly influenced by CB1R activation on central vagal pathways, whereas intestinal peristalsis can be modified by CB1R activation in the absence of extrinsic input. Actions at multiple levels make the CB1R a target for the treatment of functional bowel disorders, such as IBS. Since low-grade inflammation may act as a trigger for occurrence of IBS, CB2R modulation could be beneficial, but there is little supporting evidence for this yet. The challenge is to accomplish CBR activation while minimizing adverse effects and abuse liabilities. Potential therapeutic strategies involve increasing signaling by endocannabinoids (EC). The pathways involved in the biosynthesis, uptake and degradation of EC provide opportunities for modulation of CB1R and some recent evidence with inhibitors of EC uptake and metabolism suggest that these could be exploited for therapeutic gain.
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PMID:Involvement of cannabinoid receptors in gut motility and visceral perception. 1510 Jan 66

Functional bowel disorders (FBDs) are defined by symptoms of gastrointestinal (GI) dysfunction, discomfort and pain in the absence of a demonstrable organic cause. Since the prevalence of FBDs, particularly functional dyspepsia and irritable bowel syndrome, can be as high as 20%, FBDs represent a significant burden in terms of direct healthcare and productivity costs. There is emerging evidence that the discomfort and pain experienced by many FBD patients is due to persistent hypersensitivity of primary afferent neurons, which may develop in response to infection, inflammation or other insults. This concept identifies vagal and spinal sensory neurons as important targets for novel therapies of GI hyperalgesia. Sensory neuron-specific targets can be grouped into three categories: receptors and sensors at the peripheral nerve terminals, ion channels relevant to nerve excitability and conduction and transmitter receptors. Particular therapeutic potential is attributed to targets that are selectively expressed by afferent neurons, such as the transient receptor potential channel TRPV1, acid-sensing ion channels and tetrodotoxin-resistant Na + channels.
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PMID:Gastrointestinal pain in functional bowel disorders: sensory neurons as novel drug targets. 1510 53

Irritable bowel syndrome is a chronic disease involving pain or discomfort relieved by defecation and associated with a change in frequency or consistency of the stools. The effect of abdominoplasty on patients with irritable bowel syndrome has not been elucidated, so advising patients with irritable bowel syndrome about the effects of surgery on their disease was difficult. One hundred female patients from a pool of 120 patients responded to a questionnaire relating to abdominoplasty surgery. Follow-up ranged from 6 months to 2 years. Patients completed questionnaires formulated on the basis of Rome II Diagnostic Criteria. Of the 100 patients, nine had true irritable bowel syndrome, nine had moderate symptoms and were receiving medication (not true irritable bowel syndrome), 16 had mild symptoms on occasional medication, and 66 had no symptoms of irritable bowel syndrome before surgery. Of the true irritable bowel syndrome patients, all had symptomatic improvement with decreased medication, eight of the nine patients with moderate symptoms improved markedly, and five of the 16 patients with mild symptoms improved significantly. No patient had any initiation or deterioration of symptoms. It is thus concluded that the symptoms of irritable bowel syndrome are certainly not worsened, in the short term, by surgery, and may be alleviated or improved in most significant cases.
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PMID:Irritable bowel syndrome and abdominoplasty. 1510 5

The neurocognitive pathways by which placebo effects operate are poorly understood. Positron emission tomography (PET) imaging was used to assess the brain response of patients with chronic abdominal pain (irritable bowel syndrome; IBS) to induced intestinal discomfort both before and after a 3-week placebo regimen. A daily symptom diary was used to measure symptom improvement. Increases in right ventrolateral prefrontal cortex (RVLPFC) activity from pre- to post-placebo predicted self-reported symptom improvement, and this relationship was mediated by changes in dorsal anterior cingulate (dACC), typically associated with pain unpleasantness. These results are consistent with disruption theory [Lieberman, M.D., 2003. Reflective and reflexive judgment processes: a social cognitive neuroscience approach. In: Forgas, J.P., Williams, K.R., von Hippel, W. (Eds.), Social Judgments: Explicit and Implicit Processes. Cambridge Univ. Press, New York, pp. 44-67], which proposes that activation of prefrontal regions associated with thinking about negative affect can diminish dACC and amygdala reactivity to negative affect stimuli. This is the first study to identify a neural pathway from a region of the brain associated with placebos and affective thought to a region closely linked to the placebo-related outcome of diminished pain unpleasantness.
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PMID:The neural correlates of placebo effects: a disruption account. 1511 38

Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder, affecting about 20% of the world's population. Chronic abdominal pain or discomfort relieved by defecation and associated with altered bowel habits are the mainstay in diagnosis. The pathophysiology of IBS remains unknown. This biopsychosocial disorder involves dysregulation of the nervous system, altered intestinal motility, and increased visceral sensitivity. All of these result from dysregulation of the bidirectional communication between the gut with its enteric nervous system and the brain (the brain-gut axis), modulated by various psychosocial and environmental factors (e.g. infection, inflammation). Numerous neurotransmitters are found in the brain and gut that regulate GI activities, including 5-hydroxytryptamine (5-HT, serotonin) and its 5-HT3 and 5-HT4 receptors. The current approach to IBS patients is based on a positive diagnosis of the symptom complex, exclusion of underlying organic disease, and institution of a therapeutic trial. Traditional symptomatic treatment has included antidiarrheals, laxatives and bulking agents/fiber, low-dose tricyclic antidepressants, antispasmodics for pain, and "alternative" therapies (e.g. psychotherapy, hypnotherapy). The scientific evidence supporting this therapy is limited. Novel approaches include visceral analgesics and serotonin agonists and antagonists. In patients with severe diarrhea, 5-HT3 receptor antagonists (e.g. alosetron) and selective M3-type anticholinergics are indicated, in constipation 5-HT4 agonists (e.g. tegaserod), and in pain alfa2-adrenergics (e.g. clonidine), cholecystokinin antagonists, kappa-opioid agonists (e.g. fedotozine), and neurokinin antagonists; some of these agents are still being investigated. Understanding the brain-gut axis is crucial in the development of effective therapies for IBS.
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PMID:The brain-gut axis in irritable bowel syndrome--clinical aspects. 1517 82

Despite many studies on pain of functional gastrointestinal disorders (FGID), the pain mechanism of FGID is not well understood, and pain treatment of FGID is not established. Following our former functional dyspepsia (FD) study, we proposed two subgroups of patients with irritable bowel syndrome (IBS), pain and discomfort (not pain). The duration of disease of discomfort IBS patients was longer than that of pain IBS patients (P < 0.05) The rate of anxiety disorder of pain IBS patients tended to be higher than that of discomfort IBS patients (P = 0.07172). Fifteen (15.2%) of 99 pain IBS patients and 1 (3.4%) of 29 discomfort IBS patients overlapped FD (P < 0.1). We expected that a common psychosocial mechanism would influence both pain dyspepsia patients and pain IBS patients, however, there were some differences between these FGID patients with pain. Anxiety in IBS patients with lower gastrointestinal pain seems to be important in their treatment.
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PMID:What does pain or discomfort in irritable bowel syndrome mean? 1518 60


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