Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder defined
May 8, 2019
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF GSI-IX manufacturer and receptors might be a key molecule involving the immune and movement function brainCgut axis in IBS. and reduced to the onset IBS (1, 6). There is evidence that this luminal microbiota affects GI motility by interacting with muscularis macrophage and enteric neurons (7). In a prospective trial, IBS patients receiving showed decreased-depression scores, improved quality of life scores, and overall symptoms (8). Investigators have also suggested that small-intestinal bacterial overgrowth might contribute to IBS progression (9). There is evidence to support GSI-IX manufacturer the role of moderate intestinal inflammation in the etiology of IBS. Researchers have found alteration in inflammatory mediators in the GI tract as well as in the peripheral blood circulation of animal and patient with IBS. Patients reported the onset of postinfectious IBS, a subset of IBS, after contracting viral, bacterial, protozoa, and nematode infections (6, 9). There are experimental models showing that inflammation, even if mild, could lead to long-term changes in GI nerve and easy muscle function, resulting in dysmotility, hypersensitivity (1, 7, 9, 10). ROME IV uses a biopsychosocial conceptual GSI-IX manufacturer model to explain the susceptibility to develop IBS. This means that IBS is the product of interactions between various factors and stress (1). Psychological and physical stresses exacerbate GI symptoms. IBS patients also suffer from psychiatric disorders such as stress and depressive disorder (9, 11). Animal and human studies have exhibited that stress stimulates colonic motor function, reflected by decreased-colonic transit time, increased contractile activity, the induction of defecation, and symptoms of diarrhea. There is also evidence to support that stress affects gut-pain threshold, mucosal secretory function, barrier functions, and visceral inflammatory response (1, 4). Irritable bowel syndrome patients more often have a family history of IBS (1). A search for candidate genes to reinforce the hypothesis that environmental factors play an important role in the pathogenesis of IBS has led to the association of serotonin transporter gene and cholecystokinin A receptor gene with IBS. It has been found that patients with IBS-D have a functional polymorphism in the serotonin transporter gene (6). CRF Mechanism in IBS The hypothalamic-pituitary-adrenal (HPA) axis is crucial in maintaining homeostasis and plays an important role in responses of the endocrine system GSI-IX manufacturer and behavioral activity to various stresses. Corticotropin-releasing factor (CRF or CRH) plays a pivotal and well-established role in activating the HPA axis under basal and stress conditions (12). There is convergent evidence indicating the presence of CRF, Ucns, CRFR1, and CRFR2 in various peripheral tissues such as GI tract, heart, lungs, spleen, testis and adipose tissue, and CNS. CRF, Ucns, and CRF receptors have been identified in myenteric neuron, sensory nerve, sympathetic nerve, enterochromaffin cell, and immune cells in the intestine of animals and human. This indicates that both central and peripheral CRF systems modulate the body response to stress and modulate syndromes that GSI-IX manufacturer occurs in IBS (11C14). Early weaning stress in pigs (15C21 days) causes impaired intestinal mucosal function. A decreased-CRF protein, an increased-CRFR2 protein, and no change in CRFR1 protein was detected in jejunum of late weaned pigs. Blocking both CRFR1 and CRFR2 improved disturbances in barrier function, whereas blocking CRFR2 leads to an enhanced barrier dysfunction, showing that dysfunction and hypersecretion is mediated by CRFR1 (15). Central administration of CRF induced colonic hypersensitivity in low-anxiety rats (Fischer 344); this effect was inhibited by pretreatment with CRFR1 antagonist (16). Water-avoidance stress and injection of CRF increased fecal pellet output which Cav1.3 is inhibited by CRFR1/R2 antagonist and CRFR1 antagonist CP-154,526 (17). Therefore, CRF its CRF receptors affects smooth muscle contractility, mucosal permeability, mucosal transport, and visceral pain sensitivity, indicating possible correlation with colonic manifestations of IBS (4, 11, 13). To study the mechanism of IBS, many animal models have been developed. Various approaches using chemical, mechanical stimulation, and physiological/psychological stress such as drugs, colorectal distention,.