Serotonergic Integration In the Intestinal Mucosa

2020 ◽  
Vol 26 (25) ◽  
pp. 3010-3014 ◽  
Author(s):  
Jackie D. Wood
Keyword(s):  
Abdominal Pain ◽  
Mast Cells ◽  
Substance P ◽  
Serine Proteases ◽  
Enterochromaffin Cells ◽  
Mucosal Inflammation ◽  
Watery Diarrhea ◽  
Paracrine Signaling ◽  
Acute Watery Diarrhea ◽  
Spinal Afferents

Mucosal serotonin (5-HT) is a key paracrine signaling molecule in the integrated physiology of enterochromaffin cells, enteric mast cells, spinal afferent nerves and the enteric nervous system (ENS). Enterochromaffin cells release 5-HT as a paracrine signal to enteric mast cells, spinal afferents and neurons in the ENS. Enteric mast cells release multiple mediators of paracrine signaling, among which are histamine and the serine proteases, chymase and tryptase, as well as serotonin. Some of these mediators diffuse to receptors on afferent nociceptive and mechanosensitive terminals and sensitize the terminals in a manner that may underlie abdominal pain and distension induced pain in the irritable bowel syndrome. Substance P and calcitonin gene-related peptide (CGRP), released by spinal afferent innervation, degranulate enteric mast cells. Substance P and CGRP are significant factors in mucosal inflammation evoked by bacteria in the colonic microbiome. Binding of immunoglobulin antibodies to FcεRI receptors, on enteric mast cells, degranulate the mast cells and release paracrine mediators that overlay integrative microcircuitry in the ENS. An overlay of histamine “calls up” from the ENS library of programed gut behaviors, a defensive program consisting of a sequence of copious mucosal secretions, increased blood flow and powerful orthograde propulsion organized to move threats out of the colonic lumen. Symptoms of acute watery diarrhea, cramping abdominal pain and incontinence are associated with “running” of the defense program. Intestinal behavioral programs stored in the ENS library are described as working like digital “apps”.

M1221 The Role of Substance P and Mast Cells as Immunohistologic Biomarkers for Chronic Abdominal Pain in Children

2010 ◽  
Vol 138 (5) ◽  
pp. S-357
Author(s):  
Wendy A. Henderson ◽  
Tara J. Taylor ◽  
Ravi Shankar ◽  
Miriam R. Anver ◽  
Donna O. Butcher ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Mast Cells ◽  
Substance P ◽  
Chronic Abdominal Pain

scholarly journals The Evolving Role of Mucosal Histology in the Evaluation of Pediatric Functional Dyspepsia: A Review

2019 ◽  
Vol 1 (1) ◽  
pp. 176-190 ◽  
Author(s):  
Craig A. Friesen ◽  
Jennifer M. Colombo ◽  
Jennifer V. Schurman
Keyword(s):  
Abdominal Pain ◽  
Mast Cells ◽  
Children And Adolescents ◽  
Clinical Significance ◽  
Diagnostic Yield ◽  
Mucosal Inflammation ◽  
Organic Disease ◽  
Mucosal Biopsy ◽  
Rule Out

Although not required to establish the diagnosis, endoscopy with mucosal biopsy is commonly performed in the evaluation of children with dyspepsia. Traditionally, esophagogastroduodenoscopy (EGD) has been performed in children with abdominal pain to identify pathology or conversely, to “rule-out” organic disease in order to establish a diagnosis of FD. In this review, we discuss the current diagnostic yield of endoscopically-obtained biopsies in identifying disease in children and adolescents with dyspepsia including an expanded discussion of common histologic diagnoses where clinical significance has not been definitively established. In turn, we discuss the transition of endoscopy from a search for disease to a search for biologic contributors to symptom generation, while considering the growing evidence linking non-diagnostic mucosal inflammation to FD, specifically mast cells and eosinophils.

Mast cell-nerve fiber interaction: Ultrastructural studies

1990 ◽  
Vol 48 (3) ◽  
pp. 428-429
Author(s):  
E.Y. Chi ◽  
M.L. Su ◽  
Y.T. Tien ◽  
W.R. Henderson
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Nerve Fiber ◽  
Sensory Nerves ◽  
Ultrastructural Studies ◽  
Morphological Studies ◽  
Granulocyte Infiltration ◽  
Intracutaneous Injection ◽  
Recent Attention

Recent attention has been directed to the interaction of the nerve and immune systems. The neuropeptide substance P, a tachykinnin which is a neurotransmitter in the central and peripheral nervous systems produces tissue swelling, augemntation of intersitial fibrin deposition and leukocyte infiltration after intracutaneous injection. There is a direct correlation reported between the extent of mast cell degranulation at the sites of injection and the tissue swelling or granulocyte infiltration. It has previously been demonstrated that antidromic electrical stimulation of sensory nerves induces degranulation of cutaneous mast cells, cutaneous vasodilation and augmented vascular permeability. Morphological studies have documented a close anatiomical association between mast cells and nonmyelinated nerves, that contain substance P and other neuropeptides. However, the presence of mast cells within nerve fasicles has not been previously examined ultrastructurally. In this study, we examined ultrastructurally the distribution of mast cells in the nerve fiber bundles located in the muscular connective tissue of rat tongues (n=20).

scholarly journals A9 DORSAL ROOT GANGLIA NEURONAL RESPONSES AND SUBSTANCE P PRODUCTION ARE HIGHER IN MALE MICE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 10-11
Author(s):  
J Pujo ◽  
G De Palma ◽  
J Lu ◽  
S M Collins ◽  
P Bercik
Keyword(s):  
Abdominal Pain ◽  
Substance P ◽  
Gut Microbiota ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Neuronal Response ◽  
Neuronal Responses ◽  
Visceral Sensitivity ◽  
Germ Free

Abstract Background Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Sex also appears to play a key role in visceral sensitivity, as women report more abdominal pain than men. Thus, both gut bacteria and sex are important in the regulation of gut nociception, but the underlying mechanisms remain poorly understood. Aims To investigate the role of gut microbiota and sex in abdominal pain. Methods We used primary cultures of sensory neurons from dorsal root ganglia (DRG) of female and male conventionally raised (SPF) or germ-free (GF) mice (7–18 weeks old). To study the visceral afferent activity in vitro, calcium mobilization in DRG sensory neurons was measured by inverted fluorescence microscope using a fluorescent calcium probe Fluo-4 (1mM). Two parameters were considered i) the percentage of responding neurons ii) the intensity of the neuronal response. First, DRG sensory neurons were stimulated by a TRPV1 agonist capsaicin (12.5nM, 125nM and 1.25µM) or by a mixture of G-protein coupled receptors agonist (GPCR: bradykinin, histamine and serotonin; 1µM, 10µM and 100µM). We next measured the neuronal production of substance P and calcitonin gene-related peptide (CGRP), two neuropeptides associated with nociception, in response to capsaicin (1.25µM) or GPCR agonists (100µM) by ELISA and EIA, respectively. Results The percentage of neurons responding to capsaicin and GPCR agonists was similar in male and female SPF and GF mice. However, the intensity of the neuronal response was higher in SPF male compared to SPF female in response to capsaicin (125nM: p=0.0336; 1.25µM: p=0.033) but not to GPCR agonists. Neuronal activation was similar in GF and SPF mice of both sexes after administration of capsaicin or GPCR agonists. Furthermore, substance P and CGRP production by sensory neurons induced by capsaicin or GPCR agonists was similar in SPF and GF mice, regardless of sex. However, while the response to capsaicin was similar, the GPCR agonists-induced production of substance P was higher in SPF male mice compared to SPF females (p=0.003). The GPCR agonists-induced production of CGRP was similar in SPF male and female mice. Conclusions Our data suggest that at the level of DRG neurons, the absence of gut microbiota does not predispose to visceral hypersensitivity. The intensity of DRG neuronal responses to capsaicin and the GPCR agonists-induced production of substance P are higher in male compared to female mice, in contrast to previously published studies in various models of acute and chronic pain. Further studies are thus needed to investigate the role of sex in visceral sensitivity. Funding Agencies CIHR

Clinical Trial of Glucose-Oral Rehydration Solution (ORS), Rice Dextrin-ORS, and Rice Flour-ORS for the Management of Children With Acute Diarrhea and Mild or Moderate Dehydration

PEDIATRICS ◽  
1995 ◽  
Vol 95 (2) ◽  
pp. 191-197
Author(s):  
Susana Molina ◽  
Carolina Vettorazzi ◽  
Janet M. Peerson ◽  
Noel W. Solomons ◽  
Kenneth H. Brown
Keyword(s):  
Clinical Trial ◽  
Treatment Group ◽  
Acute Diarrhea ◽  
Oral Rehydration Solution ◽  
Rice Flour ◽  
Watery Diarrhea ◽  
Hydration Status ◽  
Oral Rehydration ◽  
Acute Watery Diarrhea ◽  
Rehydration Solution

Objective. To assess the effects of glucose (G)-oral rehydration solution (ORS), rice dextrin (RD)-ORS, and rice flour (RF)-ORS on fluid intake, rapidity of rehydration, and stool output of children with acute diarrhea and mild or moderate dehydration. Methods. The study was a randomized, double-masked clinical trial. One hundred forty-six male infants, ages 3 to 36 months, were randomly assigned to one of three treatment groups. Clinical evaluations and fluid balances were conducted every 2 to 4 hours for 48 hours. Principal outcome variables were ORS consumption, recovery of hydration status, and fecal output. Results. The groups were similar at admission with regard to age, nutritional status, history of the current episode, and clinical status. There were no differences in ORS consumption by treatment group during any period of study. During the first 6-hour period, patients in group RF had less stool output (16 ± 14 g/kg/body weight) than those in group G (22 ± 20 g/kg) or RD (21 ± 19 g/kg; P < .05). After 12 hours of hospitalization, there were no differences by treatment group. Recovery of hydration status, changes in serum sodium and potassium, and duration of diarrhea in the hospital were similar in all three groups. Conclusion. There was a 24% to 27% reduction in stool output during the first 6 hours of treatment among children who received RF-ORS compared with those who received G-ORS or RD-ORS, but this effect did not persist after the first 12 hours of therapy. Because this difference was of small magnitude and limited duration, it has minor clinical importance. Thus, we conclude that the three solutions had similar efficacy for children with acute, watery diarrhea and mild or moderate dehydration.

Comparison of Regular and Probiotic Yogurts in Treatment of Acute Watery Diarrhea in Children

2017 ◽  
Vol 05 (01) ◽  
Author(s):  
Alireza Sharif ◽  
Davood Kheirkhah ◽  
Parisa Shams Esfandabadi ◽  
Seyed Behrooz Masoudi ◽  
Neda Mirbagher Ajorpaz ◽  
...  
Keyword(s):  
Watery Diarrhea ◽  
Acute Watery Diarrhea
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