Psychological stress and the severity of post-inflammatory visceral hyperalgesia.
OBJECTIVE
Lowered visceral sensory thresholds are a key finding in at least a subgroup of patients with functional bowel disorders. Stress and inflammation contribute to this altered visceral sensory function. We aimed to elucidate the role of repetitive stress and acute mucosal inflammation, alone and in combination, on sensory function.


METHODS
In randomized order, trinitrobenzenesulfonic acid (TNBS) plus the equal amount of ethanol or saline were instilled into the colorectum of female Lewis rats. Colorectal distensions (CRD) were performed with a barostat device (3 min/40 mmHg); to quantify the visceromotor response (VMR) to CRD, electromyographic activity (EMG) of the abdominal muscles was recorded. In randomized order, equal numbers of both treatment groups underwent either seven days (1 h/day) repetitive water avoidance stress (WAS) or sham WAS. CRD's were conducted 28 days later. Colonic tissue samples were obtained to characterize inflammation and blood samples were taken at day 28 to measure plasma IL-2 levels by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Compared to controls (662+/-114 microV) TNBS (1081+/-227 microV), WAS (1366+/-125 microV) and the combination of both (1477+/-390 microV) significantly augmented the VMR to CRD. TNBS and/or WAS caused significant inflammatory changes at day 5, while only TNBS+WAS also showed signs of mucosal inflammation on day 14 and significantly elevated IL-2 levels on day 28.


CONCLUSIONS
Stress and inflammation cause long lasting alterations of visceral sensory function. Concomitant stress further increases post-inflammatory visceral hyperalgesia.
Royal Adelaide Hospital, Department of Gastroenterology, Hepatology and General Medicine, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.
Tobias
T
Liebregts
Birgit
B
Adam
Anton
A
Bertel
Carolin
C
Lackner
Jens
J
Neumann
Nicholas J
NJ
Talley
Guido
G
Gerken
Gerald
G
Holtmann
D000009:Abdominal Muscles / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D003106:Colon / Q000294:innervation / Q000473:pathology; D004106:Dilatation; D004195:Disease Models, Animal; D004327:Drinking Behavior; D004576:Electromyography; D000431:Ethanol; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D007376:Interleukin-2 / Q000097:blood; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012007:Rectum / Q000294:innervation / Q000473:pathology; D012720:Severity of Illness Index; D012997:Solvents; D013315:Stress, Psychological / Q000503:physiopathology*; D014302:Trinitrobenzenesulfonic Acid; D014781:Viscera; D017833:Visceral Afferents / Q000503:physiopathology*
D007376:Interleukin-2; D012997:Solvents; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid