title: Severity of mucosal inflammation as a predictor for alterations of visceral sensory function in a rat model.
abstract: Transient inflammation is known to alter visceral sensory function and frequently precede the onset of symptoms in a subgroup of patients with irritable bowel syndrome (IBS). Duration and severity of the initial inflammatory stimulus appear to be risk factors for the manifestation of symptoms. Therefore, we aimed to characterize dose-dependent effects of trinitrobenzenesulfonic acid (TNBS)/ethanol on: (1) colonic mucosa, (2) cytokine release and (3) visceral sensory function in a rat model. Acute inflammation was induced in male Lewis rats by single administration of various doses of TNBS/ethanol (total of 0.8, 0.4 or 0.2 ml) in test animals or saline in controls. Assessment of visceromotor response (VMR) to colorectal distensions, histological evaluation of severity of inflammation, and measurement of pro-inflammatory cytokine levels (IL-2, IL-6) using enzyme-linked immunosorbent assay (ELISA) were performed 2h and 3, 14, 28, 31 and 42 days after induction. Increased serum IL-2 and IL-6 levels were evident prior to mucosal lesions 2h after induction of colitis and persist up to 14 days (p<0.05 vs. saline), although no histological signs of inflammation were detected at 14 days. In the acute phase, VMR was only significantly increased after 0.8 ml and 0.4 ml TNBS/ethanol (p<0.05 vs. saline). After 28 days, distension-evoked responses were persistently elevated (p<0.05 vs. saline) in 0.8 and 0.4 ml TNBS/ethanol-treated rats. In 0.2 ml TNBS/ethanol group, VMR was only enhanced after repeated visceral stimulation. Visceral hyperalgesia occurs after a transient colitis. However, even a mild acute but asymptomatic colitis can induce long-lasting visceral hyperalgesia in the presence of additional stimuli.
authors.affiliation: Royal Adelaide Hospital, Department of Gastroenterology, Hepatology and General Medicine, University of Adelaide, Australia.
authors.forename: Birgit
authors.initials: B
authors.lastname: Adam
authors.forename: Tobias
authors.initials: T
authors.lastname: Liebregts
authors.forename: Juergen M
authors.initials: JM
authors.lastname: Gschossmann
authors.forename: Constanze
authors.initials: C
authors.lastname: Krippner
authors.forename: Franziska
authors.initials: F
authors.lastname: Scholl
authors.forename: Marcus
authors.initials: M
authors.lastname: Ruwe
authors.forename: Gerald
authors.initials: G
authors.lastname: Holtmann
mesh_terms: D000009:Abdominal Muscles / Q000294:innervation; D000208:Acute Disease; D000818:Animals; D002404:Catheterization; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D003106:Colon; D004108:Dilatation, Pathologic / Q000503:physiopathology; D004195:Disease Models, Animal; D004576:Electromyography; D004797:Enzyme-Linked Immunosorbent Assay; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007376:Interleukin-2 / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000209:etiology / Q000503:physiopathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012007:Rectum; D012678:Sensation Disorders / Q000209:etiology*; D012720:Severity of Illness Index; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D014302:Trinitrobenzenesulfonic Acid