Psychological stress and the severity of post-inflammatory visceral hyperalgesia

Abstract

Objectives: 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 μV) TNBS (1081 ± 227 μV), WAS (1366 ± 125 μV) and the combination of both (1477 ± 390 μV) 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