title: Alterations in the brain-gut axis underlying visceral chemosensitivity in Nippostrongylus brasiliensis-infected mice.
abstract: OBJECTIVE
  Visceral hypersensitivity, a hallmark of irritable bowel syndrome, is generally considered to be mechanosensitive in nature and mediated via spinal afferents. Both stress and inflammation are implicated in visceral hypersensitivity, but the underlying molecular mechanisms of visceral hypersensitivity are unknown.
  
  
  METHODS
  Mice were infected with Nippostrongylus brasiliensis (Nb) larvae, exposed to environmental stress and the following separate studies performed 3-4 weeks later. Mesenteric afferent nerve activity was recorded in response to either ramp balloon distention (60 mm Hg), or to an intraluminal perfusion of hydrochloric acid (50 mmol/L), or to octreotide administration (2 micromol/L). Intraperitoneal injection of cholera toxin B-488 identified neurons projecting to the abdominal viscera. Fluorescent neurons in dorsal root and nodose ganglia were isolated using laser-capture microdissection. RNA was hybridized to Affymetrix Mouse whole genome arrays for analysis to evaluate the effects of stress and infection.
  
  
  RESULTS
  In mice previously infected with Nb, there was no change in intestinal afferent mechanosensitivity, but there was an increase in chemosensitive responses to intraluminal hydrochloric acid when compared with control animals. Gene expression profiles in vagal but not spinal visceral sensory neurons were significantly altered in stressed Nb-infected mice. Decreased afferent responses to somatostatin receptor 2 stimulation correlated with lower expression of vagal somatostatin receptor 2 in stressed Nb-infected mice, confirming a link between molecular data and functional sequelae.
  
  
  CONCLUSIONS
  Alterations in the intestinal brain-gut axis, in chemosensitivity but not mechanosensitivity, and through vagal rather than spinal pathways, are implicated in stress-induced postinflammatory visceral hypersensitivity.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Aerssens
authors.forename: Kirk
authors.initials: K
authors.lastname: Hillsley
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Peeters
authors.forename: Ronald
authors.initials: R
authors.lastname: de Hoogt
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stanisz
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Lin
authors.forename: Ilse
authors.initials: I
authors.lastname: Van den Wyngaert
authors.forename: Hinrich W
authors.initials: HW
authors.lastname: Göhlmann
authors.forename: David
authors.initials: D
authors.lastname: Grundy
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Stead
authors.forename: Bernard
authors.initials: B
authors.lastname: Coulie
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D006851:Hydrochloric Acid / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000294:innervation*; D008643:Mesentery / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000472:pathogenicity*; D009620:Nodose Ganglion / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015282:Octreotide / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000235:genetics; D017206:Strongylida Infections / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017833:Visceral Afferents / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D017481:Receptors, Somatostatin; D012313:RNA; D002772:Cholera Toxin; C093733:somatostatin receptor 2; D006851:Hydrochloric Acid; D015282:Octreotide