scholarly journals Experimental Models of Irritable Bowel Syndrome and the Role of the Enteric Neurotransmission

2017 ◽  
Author(s):  
Maria Giuliana Vannucchi ◽  
Stefano Evangelista
Keyword(s):  
Irritable Bowel Syndrome ◽  
Maternal Separation ◽  
Visceral Pain ◽  
Gastrointestinal Diseases ◽  
Experimental Models ◽  
Main Role ◽  
Cellular Mechanisms ◽  
Neonatal Maternal Separation ◽  
Irritable Bowel

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animals models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.

Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome

2007 ◽  
Vol 292 (3) ◽  
pp. G849-G856 ◽  
Author(s):  
Tian-Hua Ren ◽  
Justin Wu ◽  
David Yew ◽  
Eric Ziea ◽  
Lixing Lao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Life Stress ◽  
Maternal Separation ◽  
Visceral Pain ◽  
Surrogate Marker ◽  
Sensory Response ◽  
Withdrawal Reflex ◽  
Neonatal Maternal Separation ◽  
Irritable Bowel

Early life stress has been implicated as a risk factor for irritable bowel syndrome (IBS). We studied the effect of neonatal maternal separation on the visceromotor response and the expression of c- fos, 5-HT, and its receptors/transporters along the brain-gut axis in an animal model of IBS. Male neonatal Sprague-Dawley rats were randomly assigned to a 3-h daily maternal separation (MS) or nonhandling (NH) on postnatal days 2–21. Colorectal balloon distention (CRD) was performed for assessment of abdominal withdrawal reflex as a surrogate marker of visceral pain. Tissues from dorsal raphe nucleus in midbrain, lumbar-sacral cord, and distal colon were harvested for semiquantitative analysis of c- fos and 5-HT. The expression of 5-HT expression, 5-HT3 receptors, and 5-HT transporter were analyzed by RT-PCR. Pain threshold was significantly lower in MS than NH rats. The abdominal withdrawal reflex score in response to CRD in MS rats was significantly higher with distension pressures of 40, 60, and 80 mmHg. In MS rats, the number of c- fos-like immunoreactive nuclei at dorsal horn of lumbar-sacral spinal cord increased significantly after CRD. 5-HT content in the spinal cord of MS rats was significant higher. In the colon, both 5-HT-positive cell number and 5-HT content were comparable between MS and NH groups before CRD. Post-CRD only MS rats had significant increase in 5-HT content. Protein and mRNA expression levels of 5-HT3 receptors and 5-HT transporter were similar in MS and NH rats. Neonatal maternal separation stress predisposes rats to exaggerated neurochemical responses and visceral hyperalgesia in colon mimicking IBS.

scholarly journals Peripheral Mechanisms of Symptom Generation in Irritable Bowel Syndrome

2001 ◽  
Vol 15 (suppl b) ◽  
pp. 14B-16B ◽  
Author(s):  
Stephen M Collins
Keyword(s):  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Experimental Models ◽  
Low Grade ◽  
Sensory Physiology ◽  
Somatic Pain ◽  
Inflammatory Stimuli ◽  
The Central Nervous System ◽  
Irritable Bowel

There is considerable interest in the mechanisms that underlie symptom generation in irritable bowel syndrome (IBS) and particularly those mechanisms peripheral to higher centres in the nervous system. While the central nervous system is important in IBS, it is restricted largely to the role of behaviour in stress perception and symptom reporting. The gut and the autonomic nervous system are principal areas of research in identifying mechanisms underlying symptom generation and in the identification of new targets for drug development. While motility changes occur in IBS, they are neither specific nor predictable, and this is one reason why drugs aimed at influencing motility patterns have enjoyed limited success to date. This success has prompted interest in sensory physiology to explain pain and other discomforts expressed by patients with IBS. Patients with IBS exhibit intolerance to rectal distension and other manoeuvres of the gut, while exhibiting normal or raised thresholds for somatic pain. The mechanisms underlying the development of hyperalgesia or allodynia in the gut remain to be determined. In other systems and experimental models, low grade inflammation is a predicable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.

The Role of Dietary Approach in Irritable Bowel Syndrome

2019 ◽  
Vol 26 (19) ◽  
pp. 3512-3520 ◽  
Author(s):  
Piero Portincasa ◽  
Antony Lembo ◽  
Ornella de Bari ◽  
Domenica M. Di Palo ◽  
Anna Maggio ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastrointestinal Tract ◽  
Intestinal Microbiota ◽  
Intestinal Motility ◽  
Gastrointestinal Diseases ◽  
Functional Disorder ◽  
First Line ◽  
Dietary Education ◽  
Irritable Bowel

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most frequent gastrointestinal diseases. In IBS multiple pathophysiological mechanisms including alterations in intestinal motility, permeability, nutrient absorption, and intestinal microbiota have been implicated. Foods are commonly reported by patients to be a trigger of symptoms and therefore are likely involved in the generation of symptoms in IBS. Among all possible therapeutic options, a first-line approach to IBS is dietary education and identification of foods potentially responsible for the onset or worsening of symptoms. Dietary approaches include reduction of gas-producing foods (i.e. fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)), lactose and gluten. Further studies are required to link the ultimate role of diets in different IBS subtypes.

scholarly journals Effect of TongXie-YaoFang on Cl−andHCO3-Transport in Diarrhea-Predominant Irritable Bowel Syndrome Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaofang Lu ◽  
Shengsheng Zhang ◽  
Cheng Yang ◽  
Zhengfang Wang ◽  
Luqing Zhao ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Maternal Separation ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Formula Group ◽  
Neonatal Maternal Separation ◽  
Combined Action ◽  
Irritable Bowel

TongXie-YaoFang (TXYF) can effectively alleviate the symptoms of diarrhea-predominant irritable bowel syndrome (D-IBS) patients. However, the curative mechanism has not been fully clarified. The study was designed to investigate the effect of TXYF on the colonic ion transport induced by serotonin (5-HT) in D-IBS rats. A method of multiple stress (neonatal maternal separation (NMS) combined with restraint stress (RS)) was used to induce the D-IBS model. The model rats were randomly divided into two groups: NMS + RS group and TXYF-formula group, and the normal control (no handling) rats were classified as NH group. In the NMS + RS group, the change of short-circuit current (ΔIsc) induced by 5-HT was lower than that in the NH and TXYF-formula groups. After removing of the extracellular Cl−orHCO3-or basolateral Na+or blocking the cystic fibrosis transmembrane conductance regulator (CFTR), Na+-K+-2Cl−cotransporter (NKCC),Na+-HCO3-cotransporter,Cl-/HCO3-exchanger, K+channel, or Na+/K+-ATPase, respectively, there was no difference in 5-HT-inducedΔIscamong the three groups. These data suggest that TXYF can regulate 5-HT-induced Cl−andHCO3-secretion, possibly mediated by the combined action of CFTR, NKCC, Na+-HCO3-cotransporter,Cl-/HCO3-exchanger, K+channel, and Na+/K+-ATPase.

scholarly journals Importance of Non-pharmacological Approaches for Treating Irritable Bowel Syndrome: Mechanisms and Clinical Relevance

2021 ◽  
Vol 1 ◽  
Author(s):  
Albert Orock ◽  
Tian Yuan ◽  
Beverley Greenwood-Van Meerveld
Keyword(s):  
Irritable Bowel Syndrome ◽  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Visceral Pain ◽  
Behavioral Therapy ◽  
Functional Gastrointestinal Disorders ◽  
Experimental Models ◽  
Environmental Signals ◽  
Irritable Bowel ◽  
And Behavior

Chronic visceral pain represents a major unmet clinical need with the severity of pain ranging from mild to so severe as to prevent individuals from participating in day-to-day activities and detrimentally affecting their quality of life. Although chronic visceral pain can be multifactorial with many different biological and psychological systems contributing to the onset and severity of symptoms, one of the major triggers for visceral pain is the exposure to emotional and physical stress. Chronic visceral pain that is worsened by stress is a hallmark feature of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Current pharmacological interventions for patients with chronic visceral pain generally lack efficacy and many are fraught with unwanted side effects. Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain; however, the molecular mechanisms underlying CBT remain incompletely understood. Preclinical studies in experimental models of stress-induced visceral pain employing environmental enrichment (EE) as an animal model surrogate for CBT are unraveling the mechanism by which environmental signals can lead to long-lasting changes in gene expression and behavior. Evidence suggests that EE signaling interacts with stress and nociceptive signaling. This review will (1) critically evaluate the behavioral and molecular changes that lead to chronic pain in IBS, (2) summarize the pharmacological and non-pharmacological approaches used to treat IBS patients, and (3) provide experimental evidence supporting the potential mechanisms by which CBT ameliorates stress-induced visceral pain.

scholarly journals Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome

2019 ◽  
Vol 316 (3) ◽  
pp. G338-G349 ◽  
Author(s):  
D. Balemans ◽  
J. Aguilera-Lizarraga ◽  
M. V. Florens ◽  
P. Jain ◽  
A. Denadai-Souza ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Pain Perception ◽  
Transient Receptor Potential ◽  
Visceral Pain ◽  
Receptor Potential ◽  
General Role ◽  
Transient Receptor ◽  
Irritable Bowel ◽  
Rectal Biopsies

Previously, we showed histamine-mediated sensitization of transient receptor potential (TRP) vanilloid 1 (TRPV1) in patients with irritable bowel syndrome (IBS). Sensitization of TRP ankyrin 1 (TRPA1) and TRP vanilloid 4 (TRPV4) are also involved in aberrant pain perception in preclinical models of somatic pain. Here, we hypothesize that in parallel with TRPV1, histamine sensitizes TRPA1 and TRPV4, contributing to increased visceral pain in patients with IBS. Rectal biopsies were collected from patients with IBS and healthy subjects (HS) to study neuronal sensitivity to TRPA1 and TRPV4 agonists (cinnamaldehyde and GSK1016790A) using intracellular Ca2+ imaging. In addition, the effect of supernatants of rectal biopsies on patients with IBS and HS was assessed on TRPA1 and TRPV4 responses in murine dorsal root ganglion (DRG) sensory neurons. Finally, we evaluated the role of histamine and histamine 1 receptor (H1R) in TRPA1 and TRPV4 sensitization. Application of TRPA1 and TRPV4 agonists evoked significantly higher peak amplitudes and percentage of responding submucosal neurons in biopsies of patients with IBS compared with HS. In HS, pretreatment with histamine significantly increased the Ca2+ responses to cinnamaldehyde and GSK1016790A, an effect prevented by H1R antagonism. IBS supernatants, but not of HS, sensitized TRPA1 and TRPV4 on DRG neurons. This effect was reproduced by histamine and prevented by H1R antagonism. We demonstrate that the mucosal microenvironment in IBS contains mediators, such as histamine, which sensitize TRPV4 and TRPA1 via H1R activation, most likely contributing to increased visceral pain perception in IBS. These data further underscore H1R antagonism as potential treatment for IBS. NEW & NOTEWORTHY We provide evidence for histamine-mediated transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 sensitization in irritable bowel syndrome (IBS) via histamine 1 receptor (H1R) activation, most likely contributing to increased visceral pain perception. Our results reveal a general role of sensory TRP channels as histamine effectors in the pathophysiology of IBS and provide novel mechanistic insights into the therapeutic potential of H1R antagonism in IBS.

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