title: Submucous rather than myenteric neurons are activated by mucosal biopsy supernatants from irritable bowel syndrome patients.
abstract: BACKGROUND
  We previously showed that colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS) activate neurons of the human submucous plexus, an area with densely packed immune cells. Based on the concept that mucosa-nerve signaling is altered in IBS, we tested in this study whether the nerve sensitizing effect of IBS mucosal biopsy supernatants is more prominent in the submucous than myenteric plexus.
  
  
  METHODS
  Fast neuroimaging with the voltage-sensitive dye Di-8-ANEPPS was used to record activity of guinea-pig submucous and myenteric neurons after application of constipation (C)- and diarrhea (D)-IBS supernatants (three each) and four supernatants from healthy control subjects. Results are based on recordings from 4731 neurons.
  
  
  RESULTS
  Control supernatants did not evoke significant responses in submucous or myenteric neurons. In contrast, all IBS supernatants evoked a significant spike discharge (median 3.6 Hz) in 46% of submucous neurons. This activation was significantly stronger than in the myenteric plexus where even twice the amount of supernatants evoked a lower spike frequency (median 2.1Hz) in only 8.5% of neurons. Pharmacological studies revealed serotonin, histamine, and proteases as components mediating neuronal activation. Individual application of these components revealed that only serotonin evoked a significantly stronger activation of submucous compared with myenteric neurons.
  
  
  CONCLUSIONS
  Direct neuronal activation by IBS mucosal biopsy supernatants is primarily a feature of submucous rather than myenteric neurons. This is associated with a stronger excitation of submucous neurons by serotonin. The plexus-specific effects support the concept that altered mucosa-nerve signaling underlies disturbances in IBS.
authors.affiliation: Human Biology, Technische Universität München, Germany. schemann@wzw.tum.de
authors.forename: S
authors.initials: S
authors.lastname: Buhner
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Berger
authors.forename: S
authors.initials: S
authors.lastname: Vignali
authors.forename: G
authors.initials: G
authors.lastname: Barbara
authors.forename: R
authors.initials: R
authors.lastname: De Giorgio
authors.forename: V
authors.initials: V
authors.lastname: Stanghellini
authors.forename: M
authors.initials: M
authors.lastname: Schemann
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000818:Animals; D001706:Biopsy; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009197:Myenteric Plexus / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D013368:Submucous Plexus / Q000187:drug effects*; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned