Repeated water avoidance stress induces visceral hypersensitivity: Role of interleukin-1, interleukin-6, and peripheral corticotropin-releasing factor.

Abstract

BACKGROUND AND AIM:

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, that is, visceromotor response (VMR) was detected electrophysiologically in conscious rats. WAS or sham stress as control for 1 h daily was loaded, and the threshold of VMR was determined before and at 24 h after the stress.

RESULTS:

Repeated WAS for three 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 before each WAS session, prevented the visceral allodynia, but the antagonist (200 μg/kg) ip at 30 min and 15 h 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 two times before the measurement abolished the response.

CONCLUSIONS:

Repeated WAS for three 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.

• Authors: Tsukasa Nozu, Saori Miyagishi, Rintaro Nozu, Kaoru Takakusaki, Toshikatsu Okumura
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 32 Issue 12 Pg. 1958-1965 (Dec 2017) ISSN: 1440-1746 [Electronic] Australia
• PMID: 28299830 (Publication Type: Journal Article)
• Copyright: © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Interleukin-1
• Interleukin-6
• Corticotropin-Releasing Hormone

Topics

• Abdominal Muscles (physiopathology)
• Animals
• Corticotropin-Releasing Hormone (physiology)
• Disease Models, Animal
• Hyperalgesia (etiology, physiopathology)
• Interleukin-1 (physiology)
• Interleukin-6 (physiology)
• Male
• Mast Cells
• Muscle Contraction
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Stress, Psychological (complications)
• Viscera