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

Physical and psychological stresses are widely accepted as triggers and / or modifiers of the clinical course of diverse gastrointestinal disorders such as peptic ulcer, irritable bowel syndrome or inflammatory bowel disease. Growing experimental evidence from a variety of models such as immobilization, thermal injury or early maternal deprivation in laboratory animals uniformly supports the ability of stress to induce the development of gastric ulcers, altered gastrointestinal motility and ion secretion, and increased intestinal permeability leading to the passage of antigens to the lamina propria and bacterial translocation. Stress can also synergize with other pathogenic factors such as Helicobacter pylori, non-steroidal anti-inflammatory drugs or colitis-inducing chemicals to produce gastrointestinal disease. The brain-gut axis provides the anatomical basis through emotions and environmental influences modulate the gastrointestinal function through the regulation of gastrointestinal immune system and mucosal inflammation; in this sense, mucosal mast cells - at cellular level - and corticotropin releasing factor (CRF) - at molecular level - seem to play a crucial role. On the other hand, an array of adaptive responses have been evolved in order to maintain the homeostasis and to ensure the survival of the individual. In the gut mucosa anti-inflammatory pathways counteract the deleterious effect of the stressful stimuli on the gastrointestinal homeostasis. In the present review we discuss the several experimental approaches used to mimic human stressful events or chronic stress in laboratory animals, the evidence of stress-induced gastrointestinal inflammation and dysfunction derived from them, and the involved cellular and molecular mechanisms that are being discovered during the last years.
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PMID:The effects of physical and psychological stress on the gastro-intestinal tract: lessons from animal models. 1853 37

Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin-releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF(1) and CRF(2) receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF(1) receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF(1) receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF(1) receptor antagonists in blunting these stress-related components. The importance of CRF(1) signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in a subset of patients.
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PMID:From Hans Selye's discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: implication in stress-related functional bowel diseases. 1912 89

Functional gastrointestinal disorders (FGIDs), which include irritable bowel syndrome (IBS), encompass a heterogeneous group of diseases identified by chronic or recurrent symptom-based diagnostic criteria. Psychosocial factors are key components in the outcome of clinical manifestations of IBS symptoms. Anxiogenic and endocrine responses to stress are mediated by the corticotropin-releasing factor (CRF)-CRF1 receptor pathway. Preclinical studies show that activation of the CRF1 receptor by exogenous CRF or stress recapitulates many functional symptoms of IBS diarrhea-predominant patients as related to anxiogenic/hypervigilant behavior, autonomic nervous system alterations, induction of diarrhea, visceral hyperalgesia, enhanced colonic motility, mucus secretion, increased permeability, bacterial translocation, and mast cell activation, which are all alleviated by selective CRF1 receptor antagonists. Clinical studies also support that CRF administration can induce IBS-like symptoms in healthy subjects and heighten colonic sensitivity in IBS patients. Yet to be ascertained is whether CRF1 receptor antagonists hold promise as a new therapy in IBS treatment.
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PMID:A role for corticotropin-releasing factor in functional gastrointestinal disorders. 1961 2

Irritable bowel syndrome is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterised by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of irritable bowel syndrome is multifactorial involving disturbances of the brain-gut axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, alpha-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride channel activators, guanylate cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed.
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PMID:Current and novel therapeutic options for irritable bowel syndrome management. 1966 53

The interaction between gut inflammatory processes and stress is gaining increasing recognition. Corticotropin-releasing factor (CRF)-receptor activation in the brain is well established as a key signaling pathway initiating the various components of the stress response including in the viscera. In addition, a local CRF signaling system has been recently established in the gut. This review summarize the present knowledge on mechanisms through which both brain and gut CRF receptors modulate intestinal inflammatory processes and its relevance towards increased inflammatory bowel disease (IBD) activity and post-infectious irritable bowel syndrome (IBS) susceptibility induced by stress.
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PMID:Stress-related modulation of inflammation in experimental models of bowel disease and post-infectious irritable bowel syndrome: role of corticotropin-releasing factor receptors. 1969 78

BACKGROUND A growing body of data implicates increased life stresses with the initiation, persistence and severity of symptoms associated with functional gut disorders such as irritable bowel syndrome (IBS). Activation of central and peripheral corticotropin-releasing factor (CRF) receptors is key to stress-induced changes in gastrointestinal (GI) function. METHODS This study utilised immunofluorescent and Western blotting techniques to investigate colonic expression of CRF receptors in stress-sensitive Wistar Kyoto (WKY) and control Sprague Dawley (SD) rats. KEY RESULTS No intra-strain differences were observed in the numbers of colonic CRFR1 and CRFR2 positive cells. Protein expression of functional CRFR1 was found to be comparable in control proximal and distal colon samples. Sham levels of CRFR1 were also similar in the proximal colon but significantly higher in WKY distal colons (SD: 0.38 +/- 0.14, WKY: 2.06 +/- 0.52, P < 0.01). Control levels of functional CRFR2 were similar between strains but sham WKYs samples had increased CRFR2 in both the proximal (SD: 0.88 +/- 0.21, WKY: 1.8 +/- 0.18, P < 0.001) and distal (SD: 0.18 +/- 0.08, WKY: 0.94 +/- 0.32, P < 0.05) regions. Exposure to open field (OF) and colorectal distension (CRD) stressors induced decreased protein expression of CRFR1 in SD proximal colons, an effect that was blunted in WKYs. CRD stimulated decreased expression of CRFR2 in WKY rats alone. Distally, CRFR1 is decreased in WKY rats following CRD but not OF stress without any apparent changes in SD rats. CONCLUSIONS & INFERENCES This study demonstrates that psychological and physical stressors alter colonic CRF receptor expression and further support a role for local colonic CRF signalling in stress-induced changes in GI function.
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PMID:Differential stress-induced alterations of colonic corticotropin-releasing factor receptors in the Wistar Kyoto rat. 1980 69

Irritable bowel syndrome (IBS) supports the concept of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. This study investigates the neuroendocrine and psychological responses to the acute physical stress of a lumbar puncture (LP) in women with diarrhea-predominant IBS by assessing central and peripheral HPA activity and affective measures. Blood samples have been collected at baseline and immediately post- and 1 hr following LP from 13 women with IBS and 13 controls. Plasma adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine levels are analyzed. A single measure of cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor (CRF(CSF)) and norepinephrine(CSF) is noted. Affective assessments are used to rate anxiety and depression with the Hospital Anxiety and Depression Scale (HADS) and acute mood state is rated using the Stress Symptom Rating questionnaire (stress, anxiety, anger, arousal). The women with IBS display blunted ACTH and cortisol responses to the LP along with a profile of affective responsiveness suggestive of chronic psychosocial stress, although no CRF(CSF) differences between groups are observed.
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PMID:Hypothalamic--pituitary-- adrenal axis dysregulation in women with irritable bowel syndrome in response to acute physical stress. 1985 23

Corticotropin-releasing factor (CRF) orchestrates the mammalian endocrine, autonomic, and behavioral stress response and has been implicated in the pathophysiology of illnesses ranging from irritable bowel syndrome to mood and anxiety disorders. CRF is produced and released from a variety of cell types, making it difficult to distinguish the specific role of CRF from other neurotransmitters with which it colocalizes. To clarify the basic biology of the CRF neuron, we must be able to manipulate selectively CRFergic cells. Here we describe a novel transgenic mouse using 3.0 kb of the CRF promoter to drive expression of Cre-recombinase (CRFp3.0Cre). Crossing CRFp3.0Cre with a fluorescent reporter strain results in Cre-dependent green fluorescent protein expression within CRF-producing cells. Thus, CRF cells can be identified for single-cell polymerase chain reaction and electrophysiological procedures. Furthermore, the CRFp3.0Cre transgenic can be combined with other available mouse strains containing a "floxed" gene of interest to allow unparalleled detailed analysis of the CRF system.
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PMID:A novel transgenic mouse for gene-targeting within cells that express corticotropin-releasing factor. 2030 68

It is well established that central corticotropin releasing factor (CRF) signaling mediates the gastrointestinal responses to stress. However, as shown in the brain, both CRF receptors and ligands are also widely expressed in the colon and the ileum of humans and rodents, and stress modulates their expression. Several functional studies documented that peripheral injection of CRF or urocortin stimulates colonic transit, motility, Fos expression in myenteric neurons, and defecation through activation of CRF(1) receptors, whereas it decreases ileal contractility via CRF(2) receptors. Additionally, intraperitoneal administration of CRF induces colonic mast cells degranulation via both CRF(1) and CRF(2) receptors and increases ion secretion and mucosal permeability to macromolecules, which can in turn promote intestinal inflammation and alter visceral sensitivity. Most peripheral CRF-induced alterations of colonic and ileal functions mimic effects which are observed after stress exposure, and CRF receptor antagonists given peripherally prevent stress-induced GI dysfunction. Furthermore, CRF peptides can reproduce secretomotor and mucosal alterations in vitro. Therefore, accumulated clinical and preclinical evidence supports in addition to the brain, a role for peripheral CRF signaling in mediating stress-induced effects on gastrointestinal sensorimotor, mucosal and immune functions, that may be components of underlying mechanisms involved in stress-related impact on inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).
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PMID:Corticotropin releasing factor signaling in colon and ileum: regulation by stress and pathophysiological implications. 2038 44

Life stress and mucosal inflammation may influence symptom onset and severity in certain gastrointestinal disorders, particularly irritable bowel syndrome (IBS), in connection with dysregulated intestinal barrier. However, the mechanism responsible remains unknown. Crowding is a validated animal model reproducing naturalistic psychosocial stress, whose consequences on gut physiology remain unexplored. Our aims were to prove that crowding stress induces mucosal inflammation and intestinal dysfunction, to characterize dynamics in time, and to evaluate the implication of stress-induced mast cell activation on intestinal dysfunction. Wistar-Kyoto rats were submitted to 15 days of crowding stress (8 rats/cage) or sham-crowding (2 rats/cage). We measured spontaneous and corticotropin-releasing factor-mediated release of plasma corticosterone. Stress-induced intestinal chrono-pathobiology was determined by measuring intestinal inflammation, epithelial damage, mast cell activation and infiltration, and intestinal barrier function. Corticosterone release was higher in crowded rats throughout day 15. Stress-induced mild inflammation, manifested earlier in the ileum and the colon than in the jejunum. While mast cell counts remained mostly unchanged, piecemeal degranulation increased along time, as the mucosal content and luminal release of rat mast cell protease-II. Stress-induced mitochondrial injury and increased jejunal permeability, both events strongly correlated with mast cell activation at day 15. Taken together, we have provided evidences that long-term exposure to psychosocial stress promotes mucosal inflammation and mast cell-mediated barrier dysfunction in the rat bowel. The notable resemblance of these findings with those in some IBS patients, support the potential interest and translational validity of this experimental model for the research of stress-sensitive intestinal disorders, particularly IBS.
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PMID:Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress. 2060 Aug 18


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