Protease-activated receptor 1 is implicated in irritable bowel syndrome mediators–induced signaling to thoracic human sensory neurons

Proteases and protease-activated receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators. Human thoracic DRG were obtained from the national disease resource interchange. Expression of PAR1, PAR2, and PAR4 was assessed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR) in whole DRG or in primary cultures of isolated neurons. Calcium signaling in response to PAR agonist peptides (PAR-AP), their inactive peptides (PAR-IP), thrombin (10 U/mL), supernatants from colonic biopsies of patients with IBS, or healthy controls, with or without PAR1 or PAR4 antagonist were studied in cultured human DRG neurons. PAR1, PAR2, and PAR4 were all expressed in human DRG, respectively, in 20%, 40%, and 40% of the sensory neurons. PAR1-AP increased intracellular calcium concentration in a dose-dependent manner. This increase was inhibited by PAR1 antagonism. By contrast, PAR2-AP, PAR4-AP, and PAR-IP did not cause calcium mobilization. PAR1-AP–induced calcium flux was significantly reduced by preincubation with PAR4-AP, but not with PAR2-AP. Thrombin increased calcium flux, which was inhibited by a PAR1 antagonist and increased by a PAR4 antagonist. Supernatants from colonic biopsies of patients with IBS induced calc...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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CONCLUSIONS: There is currently not enough evidence to assess whether biofeedback interventions are effective for controlling symptoms of IBS. Given the positive results reported in small trials to date, biofeedback deserves further study in people with IBS. Future research should include active control groups that use high provider-participant interaction, in an attempt to balance non-specific effects of interventions between groups, and report both commonly used outcome measures (e.g. IBS-SSS) and historical outcome measures (e.g. the composite primary symptom reduction (CPSR) score) to allow for meta-analysis with previ...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
AbstractIrritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and alterations in stool form and/or frequency, leading to reduced quality of life. Pharmacologic agents currently approved by the US Food and Drug Administration for treatment of IBS with diarrhea (IBS-D) in adults are the nonsystemic antibiotic rifaximin, the mixed µ- and κ-opioid receptor agonist/δ-opioid antagonist eluxadoline, and the selective serotonin 5-HT3 antagonist alosetron (the last of which is indicated only in women with severe IBS-D refractory to conventional therapy). Both eluxadoline and...
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
ConclusionsLow or very low certainty evidence indicated that there was no difference between CGEC and WCM in the treatment of IBS-D. The combination of CGEC and WCM has a better therapeutic effect than WCM alone in the treatment of IBS-D. Future large sample, multi-center and high-quality RCTs should be rigorously designed and implemented to evaluate the clinical effects and safety of CGEC for IBS-D.
Source: European Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like visceral hypersensitivity mediated by fermentation products of intestinal microbes in mice.
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research
AbstractObjectiveTo observe the clinical efficacy of acupuncture treatment for depressive symptom in diarrhea-predominant irritable bowel syndrome (IBS-D).MethodsA total of 70 patients with IBS-D accompanied by depressive symptom were randomized into a control group and an observation group, with 35 cases in each group. The control group was treated with oral intake of pinaverium bromide tablets, and the observation group was treated with regulating liver and spleen acupuncture treatment. The two groups were treated for 4 weeks. The scores of IBS symptom severity scale (IBS-SSS) and self-rating depression scale (SDS) were ...
Source: Journal of Acupuncture and Tuina Science - Category: Complementary Medicine Source Type: research
AbstractChildren with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called ‘Rapid transit constipation (RTC)’ first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment. Unexpectedly, we found that RTC occured in 29% of 1000 transit studies in a retrospective audit. Irritable bowel syndrome (IBS) occurs in 7&n...
Source: Pediatric Surgery International - Category: Surgery Source Type: research
In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch ‐clamp recording, behavioral tests, Western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out (AC1 KO) mice. Integrative approaches were used to investigate possible changes of neuronal adenylyl cyclas e 1 (AC1) in the ACC after the injury. We found that AC1, a key enzyme for pain‐related cortical plasticity, was significantly increased in the ACC in an animal model of irrit...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research
CONCLUSIONS: Patients with Chronic Fatigue Syndrome should be evaluated for current psychiatric conditions because of their impact on patient quality of life, but they do not act as a symptom multiplier for the illness. Other co-existing medically unexplained syndromes are more common than psychiatric co-morbidities in patients presenting for evaluation of medically unexplained fatigue and are also more associated with increased disability and the number and severity of symptoms. Key Messages When physicians see patients with medically unexplained fatigue, they often infer that this illness is due to an underlying psychiat...
Source: Annals of Medicine - Category: Internal Medicine Tags: Ann Med Source Type: research
Publication date: Available online 18 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): I.A.M. van Thiel, S. Botschuijver, W.J. de Jonge, J. SeppenAbstractVisceral pain, characterized by abdominal discomfort, originates from organs in the abdominal cavity and is a characteristic symptom in patients suffering from irritable bowel syndrome, vulvodynia or interstitial cystitis. Most organs in which visceral pain originates are in contact with the external milieu and continuously exposed to microbes. In order to maintain homeostasis and prevent infections, the immune- and nervous sy...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
New research discovers that receptors in the nervous system that cause itchy skin also reside in the gut, explaining chronic IBS pain.
Source: Health News from Medical News Today - Category: Consumer Health News Tags: Irritable Bowel Syndrome Source Type: news
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