scholarly journals 5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein–coupled receptor D

2018 ◽  
Vol 11 (561) ◽  
pp. eaal2171 ◽  
Author(s):  
Tereza Bautzova ◽  
James R. F. Hockley ◽  
Teresa Perez-Berezo ◽  
Julien Pujo ◽  
Michael M. Tranter ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
G Protein ◽  
Visceral Hypersensitivity ◽  
Mechanical Stimuli ◽  
Drg Neurons ◽  
G Protein Coupled Receptor ◽  
Irritable Bowel ◽  
Nerve Recordings ◽  
G Protein Coupled

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)–positive DRG neurons through a phospholipase C (PLC)– and pertussis toxin–dependent mechanism, suggesting that the effect was mediated by a G protein–coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C.

scholarly journals P2X3 Receptor in Primary Afferent Neurons Mediates the Relief of Visceral Hypersensitivity by Electroacupuncture in an Irritable Bowel Syndrome Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fang Zhang ◽  
Zhe Ma ◽  
Zhijun Weng ◽  
Min Zhao ◽  
Handan Zheng ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Receptor Protein ◽  
Resting Membrane Potential ◽  
Drg Neurons ◽  
Expression Levels ◽  
Behavioral Studies ◽  
Irritable Bowel

Background. Electroacupuncture (EA) has been confirmed effectiveness in the treatment of irritable bowel syndrome (IBS), and P2X3 receptors in the peripheral and central neurons participate in the acupuncture-mediated relief of the visceral pain in IBS. Objective. To reveal the neurobiological mechanism that P2X3 receptor of colonic primary sensory neurons in the dorsal root ganglia of the lumbosacral segment is involved in the alleviation of visceral hypersensitivity by EA in an IBS rat model. Methods. The IBS chronic visceral pain rat model was established according to the method of Al-Chaer et al. EA at the bilateral He-Mu points, including ST25 and ST37, was conducted for intervention. The behavioral studies, histopathology of colon, electrophysiology, immunofluorescence histochemistry, and real-time polymerase chain reaction assays were used to observe the role of P2X3 receptor in the colon and related DRG in relieving visceral hypersensitivity by EA. Results. EA significantly reduced the behavior scores of the IBS rats under different levels (20, 40, 60, 80 mmHg) of colorectal distention stimulation and downregulated the expression levels of P2X3 receptor protein and mRNA in colon and related DRG of the IBS rats. EA also regulated the electrical properties of the membranes, including the resting membrane potential, rheobase, and action potential of colon-associated DRG neurons in the IBS rats. Conclusion. EA can regulate the P2X3 receptor protein and mRNA expression levels in the colon and related DRG of IBS rats with visceral pain and then regulate the excitatory properties of DRG neurons.

680 Associations of Abdominal Pain and Visceral Hypersensitivity With Intestinal Microbiota in Patients With Irritable Bowel Syndrome

2015 ◽  
Vol 148 (4) ◽  
pp. S-131-S-132
Author(s):  
Yehuda Ringel ◽  
Jarkko Salojarvi ◽  
Tamar Ringel-Kulka ◽  
Ian M. Carroll ◽  
Willem M. de Vos
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Intestinal Microbiota ◽  
Visceral Hypersensitivity ◽  
Irritable Bowel

scholarly journals Age-Related Decrease in Abdominal Pain and Associated Structural- and Functional Mechanisms: An Exploratory Study in Healthy Individuals and Irritable Bowel Syndrome Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Abraham B. Beckers ◽  
Ellen Wilms ◽  
Zlatan Mujagic ◽  
Béla Kajtár ◽  
Kata Csekő ◽  
...  
Keyword(s):  
Young Adults ◽  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Visceral Hypersensitivity ◽  
Healthy Individuals ◽  
Intestinal Health ◽  
Healthy Elderly ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Irritable Bowel

Introduction: The world population is ageing, resulting in increased prevalence of age-related comorbidities and healthcare costs. Limited data are available on intestinal health in elderly populations. Structural and functional changes, including altered visceroperception, may lead to altered bowel habits and abdominal symptoms in healthy individuals and irritable bowel syndrome (IBS) patients. Our aim was to explore age-related changes in gastrointestinal symptoms and underlying mechanisms.Methods: In total, 780 subjects (IBS patients n = 463, healthy subjects n = 317) from two separate studies were included. Subjects were divided into different age groups ranging from young adult to elderly. Demographics and gastrointestinal symptom scores were collected from all participants using validated questionnaires. A subset of 233 IBS patients and 103 controls underwent a rectal barostat procedure to assess visceral hypersensitivity. Sigmoid biopsies were obtained from 10 healthy young adults and 10 healthy elderly. Expression of the visceral pain-associated receptors transient receptor potential (TRP) Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) genes were investigated by quantitative RT-PCR and immunofluorescence.Results: Both elderly IBS and healthy individuals showed significantly lower scores for abdominal pain (p < 0.001) and indigestion (p < 0.05) as compared to respective young adults. Visceral hypersensitivity was less common in elderly than young IBS patients (p < 0.001). Relative TRPA1 gene transcription, as well as TRPA1 and TRPV1 immunoreactivity were significantly lower in healthy elderly versus healthy young adults (p < 0.05).Conclusions: Our findings show an age-related decrease in abdominal pain perception. This may in part be related to decreased TRPA1 and/or TRPV1 receptor expression. Further studies are needed to reveal precise underlying mechanisms and the associations with intestinal health.

Mas‐related G protein‐coupled receptor C11 (Mrgprc11) induces visceral hypersensitivity in the mouse colon: A novel target in gut nociception?

2019 ◽  
Vol 31 (8) ◽  
Author(s):  
Samuel Van Remoortel ◽  
Hannah Ceuleers ◽  
Rohit Arora ◽  
Luc Van Nassauw ◽  
Joris G. De Man ◽  
...  
Keyword(s):  
G Protein ◽  
Visceral Hypersensitivity ◽  
G Protein Coupled Receptor ◽  
Mouse Colon ◽  
Novel Target ◽  
G Protein Coupled

scholarly journals PATOGENESIS DAN DIAGNOSIS SINDROM KOLON IRITABEL

2012 ◽  
Vol 4 (3) ◽  
Author(s):  
Edwin Jim
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Visceral Hypersensitivity ◽  
Enteric Infection ◽  
Functional Bowel Disorder ◽  
Bowel Habits ◽  
Infection Diagnosis ◽  
Rome Iii ◽  
Irritable Bowel ◽  
Bowel Disorder

Abstract: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by abdominal pain or discomfort and alterations in bowel habits. Many factors play some important roles in the development of the IBS including abnormal motility, visceral hypersensitivity, and enteric infection. Diagnosis of IBS is based on Rome III criteria.Keywords: irritable bowel syndrome, pathogenesis, diagnosisAbstrak: Sindrom kolon iritabel (SKI) adalah penyakit gastrointestinal fungsional kronik yang ditandai oleh nyeri perut atau rasa tidak enak di perut dan gangguan kebiasaan defekasi. Banyak faktor yang menyebabkan terjadinya SKI antara lain gangguan motilitas, hipersensitivitas viseral, dan pasca infeksi usus. Saat ini kriteria diagnosis yang digunakan untuk SKI ialah kriteria Roma III.Kata kunci: sindrom kolon iritabel, patogenesis, diagnosis

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