Mechanisms contributing to visceral hypersensitivity: focus on splanchnic afferent nerve signaling.
BACKGROUND
Visceral hypersensitivity is a main characteristic of functional bowel disorders and is mediated by both peripheral and central factors. We investigated whether enhanced splanchnic afferent signaling in vitro is associated with visceral hypersensitivity in vivo in an acute and postinflammatory rat model of colitis.


METHODS
Trinitrobenzene sulfonic acid (TNBS)-colitis was monitored individually by colonoscopy to confirm colitis and follow convalescence and endoscopic healing in each rat. Experiments were performed in controls, rats with acute colitis and in postcolitis rats. Colonic afferent mechanosensitivity was assessed in vivo by quantifying visceromotor responses (VMRs), and by making extracellular afferent recordings from splanchnic nerve bundles in vitro. Multiunit afferent activity was classified into single units identified as low threshold (LT), wide dynamic range (WDR), high threshold (HT), and mechanically insensitive afferents (MIA).


RESULTS
During acute TNBS-colitis, VMRs were significantly increased and splanchnic nerve recordings showed proportionally less MIA and increased WDR and HT afferents. Acute colitis gave rise to an enhanced spontaneous activity of both LT and MIA and augmented afferent mechanosensitivity in LT, WDR and HT afferents. Postcolitis, VMRs remained significantly increased, whereas splanchnic nerve recordings showed that the proportion of LT, WDR, HT and MIA had normalized to control values. However, LT and MIA continued to show increased spontaneous activity and WDR and HT remained sensitized to colorectal distension.


CONCLUSIONS
Visceral hypersensitivity in vivo is associated with sensitized splanchnic afferent responses both during acute colitis and in the postinflammatory phase. However, splanchnic afferent subpopulations are affected differentially at both time points.
Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
A
A
Deiteren
Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
J G
JG
De Man
Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
C
C
Keating
Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
W
W
Jiang
Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.|Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
H U
HU
De Schepper
Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.|Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
P A
PA
Pelckmans
Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.|Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
S M
SM
Francque
Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
B Y
BY
De Winter
D000818:Animals; D003092:Colitis / Q000503:physiopathology*; D003187:Compliance / Q000502:physiology; D004195:Disease Models, Animal; D004576:Electromyography; D008297:Male; D008365:Manometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013153:Splanchnic Nerves / Q000503:physiopathology*; D014781:Viscera / Q000294:innervation* / Q000503:physiopathology*
TNBS; afferent nerve signaling; colitis; mechanosensitivity; splanchnic nerves; visceral hypersensitivity