title: Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity.
abstract: Based on the discomfort/pain threshold during rectal distension, irritable bowel syndrome (IBS) patients may be subtyped as normo- or hypersensitive. We previously showed that mucosal biopsy supernatants from IBS patients activated enteric and visceral afferent neurons. We tested the hypothesis that visceral sensitivity is linked to the degree of neuronal activation. Normo- and hypersensitive IBS patients were distinguished by their discomfort/pain threshold to rectal balloon distension with a barostat. Using potentiometric and Ca(2+) dye imaging, we recorded the response of guinea-pig enteric submucous and mouse dorsal root ganglion (DRG) neurons, respectively, to mucosal biopsy supernatants from normosensitive (n = 12 tested in enteric neurons, n = 9 tested in DRG) and hypersensitive IBS patients (n = 9, tested in both types of neurons). In addition, we analysed the association between neuronal activation and individual discomfort/pain pressure thresholds. The IBS supernatants evoked Ca(2+) transients in DRG neurons and spike discharge in submucous neurons. Submucous and DRG neurons showed significantly stronger responses to supernatants from hypersensitive IBS patients as reflected by higher spike frequency or stronger [Ca(2+)]i transients in a larger proportion of neurons. The neuroindex as a product of spike frequency or [Ca(2+)]i transients and proportion of responding neurons correlated significantly with the individual discomfort/pain thresholds of the IBS patients. Supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons. The level of activation correlated with the individual discomfort/pain threshold pressure values. These findings support our hypothesis that visceral sensitivity is linked to activation of peripheral neurons by biopsy supernatants.
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Buhner
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Breg
authors.initials: B
authors.lastname: Braak
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany Department of Physiology, Shangdong University, Shangdong, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Kugler
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tamira
authors.initials: T
authors.lastname: Klooker
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Mira
authors.initials: M
authors.lastname: Wouters
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Jemma
authors.initials: J
authors.lastname: Donovan
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Sheila
authors.initials: S
authors.lastname: Vignali
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Gemma
authors.initials: G
authors.lastname: Mazzuoli-Weber
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: David
authors.initials: D
authors.lastname: Grundy
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands Translational Research Center for Gastrointestinal Disorders, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Boeckxstaens
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany schemann@wzw.tum.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schemann
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D020013:Calcium Signaling / Q000502:physiology; D017615:Enteric Nervous System / Q000503:physiopathology; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology; D006168:Guinea Pigs; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D017288:Pain Threshold; D055815:Young Adult