Repeated water avoidance stress (WAS) induces visceral hypersensitivity. Additionally, it is also known to activate corticotropin-releasing factor (CRF), mast cells and pro-inflammatory cytokines systems, but their precise roles on visceral sensation have not been determined definitely. The aim of the study was to explore this issue.
METHODS:
Abdominal muscle contractions induced by colonic balloon distention, i.e. visceromotor response (VMR) was detected electrophysiologically in conscious rats. WAS or sham stress as control for 1 hr daily was loaded and the threshold of VMR was determined before and at 24 hr after the stress.
RESULTS:
Repeated WAS for 3 consecutive days reduced the threshold of VMR, but sham stress did not induce any change. Astressin, a CRF receptor antagonist (50 µg/kg) intraperitoneally (ip) at 10 min prior to each WAS session prevented the visceral allodynia, but the antagonist (200 µg/kg) ip at 30 min and 15 hr before measurement of the threshold after completing 3-day stress session did not modify the response. Ketotifen, a mast cell stabilizer (3 mg/kg), anakinra, an interleukin (IL)-1 receptor antagonist (20 mg/kg) or IL-6 antibody (16.6 µg/kg) ip for 2 times before the measurement abolished the response.
CONCLUSIONS:
Repeated WAS for 3 consecutive days induced visceral allodynia which was mediated through mast cells, IL-1 and IL-6 pathways. Inhibition of peripheral CRF signaling prevented but did not reverse this response, suggesting that peripheral CRF may be an essential trigger but may not contribute to the maintenance of repeated WAS-induced visceral allodynia.
