Excitation of Enteric Neurons by Supernatants of Colonic Biopsies From Irritable Bowel Syndrome Patients (IBS) is Linked to Visceral Sensitivity

Using human intestinal biopsies to study the pathogenesis of irritable bowel syndrome

“…32 This study suggested that endogenous opioid and cytokine profiles differed between IBS-D and IBS-C. 32 Although visceral hypersensitivity is not a perfect biomarker for IBS, 3,33 it is also conceivable that discrepancies observed may be the result of pooling normo-and hypersensitive IBS patients, regardless of IBS subtype. 30 A few studies have used rectal distention with a barostat to divide IBS patients into those that are normo-or hypersensitive. 30,33 Supernatants derived from hypersensitive patients evoked increased action potential discharge in guinea pig submucosal neurons compared to those derived from normosensitive patients.…”

“…30 A few studies have used rectal distention with a barostat to divide IBS patients into those that are normo-or hypersensitive. 30,33 Supernatants derived from hypersensitive patients evoked increased action potential discharge in guinea pig submucosal neurons compared to those derived from normosensitive patients. 30 These studies provide evidence for the role of peripheral mechanisms in the expression of visceral pain and suggest that measuring visceral sensitivity may also help to understand differences in effects in IBS subtypes.…”

“…For example, mucosal biopsies were taken from different sites along the gastrointestinal tract, as outlined in Table 3; thus, it is possible that regionspecific differences may account for some of the discrepant results. Enteroendocrine cells express chromogranin A (CGA), but not all CGA-expressing enteroendocrine cells contain 5HT 66,67,70 ; it is difficult to directly compare EC cell counts quantified using CGA 30 to those using 5HT. 10,33,43,48,49,67,69,70 Differences in patient selection and exclusion criteria may also explain some of the observed discrepancies.…”

“…The use of supernatants obtained from biopsies has enabled the study of the activation of enteric and dorsal root ganglia (DRG) neurons and the sensitization of their ion channels . These studies have employed a number of different techniques including multiunit afferent recording, patch clamp recordings, neuroimaging techniques with voltage‐sensitive or calcium‐sensitive dyes, muscle contractility assessment, and behavioral outputs such as the visceromotor reflex to elegantly dissect some of the integrative mechanisms underlying visceral sensation in IBS (Fig. ).…”

Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016

“…Kurze, akute Applikationen von Schleimhautbiopsie-Überständen von RDS-Patienten aller Subtypen für wenige Sekunden aktivieren enterische Nervenzellen sowie viszerale Mechanosensoren und Schmerzfasern 152 172 173 . An der nervalen Stimulation sind neben Histamin und Serotonin besonders Proteasen beteiligt.…”