title: Vagal afferent input from the acid-challenged rat stomach to the brainstem: enhancement by interleukin-1beta.
abstract: Exposure of the gastric mucosa to back-diffusing concentrations of HCl (0.25 M, pH 0.51) stimulates vagal afferent input to the brainstem. Here we have examined whether pretreatment of rats with the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha causes sensitization of vagal afferent pathways to HCl. Rats were pretreated i.p. with interleukin-1beta, tumor necrosis factor-alpha (10 microg/kg) or their vehicle (sterile saline) 24, 48 and 96 h before intragastric administration of HCl (0.25 M, 1 ml/100 g). Activation of neurons in the nucleus tractus solitarii was visualized by c-Fos immunohistochemistry 2 h after the HCl challenge. I.p. administration of interleukin-1beta and tumor necrosis factor-alpha alone induced c-Fos in the brainstem, an effect that was gone after 24 h. At this time, however, the effect of HCl to cause expression of c-Fos in the nucleus tractus solitarii was significantly enhanced by pretreatment with interleukin-1beta and tumor necrosis factor-alpha. The sensitizing effect of i.p.-administered interleukin-1beta was sustained for more than 48 h and prevented by the interleukin-1 receptor antagonist anakinra. Intracisternal administration of interleukin-1beta and tumor necrosis factor-alpha (100 ng) failed to amplify the HCl-evoked expression of c-Fos in the brainstem. These results show that peripheral administration of the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha induces prolonged sensitization of vagal afferent pathways to gastric HCl challenge. This effect seems to arise from a peripheral action on vagal afferents and may be of relevance to gastric chemonociception.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria. peter.holzer@meduni-graz.at
authors.forename: P
authors.initials: P
authors.lastname: Holzer
authors.forename: M
authors.initials: M
authors.lastname: Danzer
authors.forename: R
authors.initials: R
authors.lastname: Schicho
authors.forename: C
authors.initials: C
authors.lastname: Samberger
authors.forename: E
authors.initials: E
authors.lastname: Painsipp
authors.forename: I T
authors.initials: IT
authors.lastname: Lippe
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002946:Cisterna Magna; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D006851:Hydrochloric Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D007267:Injections; D007274:Injections, Intraperitoneal; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology; D007441:Intubation, Gastrointestinal; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D016760:Proto-Oncogene Proteins c-fos; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D006851:Hydrochloric Acid