Acute distal colitis impairs gastric emptying in rats via an extrinsic neuronal reflex pathway involving the pelvic nerve.
OBJECTIVE
Patients with inflammatory bowel disease often present with abnormal gut motility away from the inflammatory site. We studied remote motility disturbances and their pathophysiology in a rat model of colitis.


METHODS
Colitis was induced 72 h prior to experiments using trinitrobenzene sulphate (TNBS) instillation. Inflammation was verified using histology and myeloperoxidase (MPO) measurements. To assess gut motility, we determined gastric emptying, distal front and geometric centre (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. The effects of hexamethonium (20 mg/kg), capsaicin (125 mg/kg) and pelvic nerve section on colitis induced motility changes were evaluated. c-Fos expression was studied in the pelvic nerve dorsal root ganglion (DRG) S1.


RESULTS
Colitis reduced gastric emptying from 38.4 (3.6)% in controls to 22.7 (4.4)% in TNBS treated rats in the absence of local gastric inflammation. Colitis had no effect on the distal front or on the geometric centre of small intestinal transit. Hexamethonium reduced gastric emptying in controls to 26.3 (4.1)% but restored it to 35.8 (4.4)% in TNBS treated rats. Capsaicin significantly impaired gastric emptying in controls from 33.1 (5.2)% to 9.5 (3.3)% while this effect was less pronounced in TNBS treated rats (from 19.2 (2.3)% to 11.5 (3.8)%; NS). In TNBS treated rats, pelvic nerve section completely restored gastric emptying from 19.8 (5.3)% to 52.5 (6.3)% without any effect on gastric emptying in control rats. TNBS colitis induced de novo c-Fos expression in the DRG S1.


CONCLUSIONS
Experimental colitis in rats delays gastric emptying via a neuronal pathway involving pelvic afferent nerve hyperactivity.
De Schepper
H U
HU
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
De Man
J G
JG
Van Nassauw
L
L
Timmermans
J-P
JP
Herman
A G
AG
Pelckmans
P A
PA
De Winter
B Y
BY
D000208:Acute Disease; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000503:physiopathology; D005730:Ganglionic Blockers / Q000494:pharmacology; D005746:Gastric Emptying / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D005772:Gastrointestinal Transit / Q000502:physiology; D018589:Gastroparesis / Q000473:pathology / Q000503:physiopathology; D018738:Hexamethonium / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010388:Pelvis / Q000294:innervation*; D009195:Peroxidase / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
D018712:Analgesics, Non-Narcotic; D005730:Ganglionic Blockers; D016760:Proto-Oncogene Proteins c-fos; D018738:Hexamethonium; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D002211:Capsaicin