Brain corticotropin-releasing factor signaling: Involvement in acute stress-induced visceral analgesia in male rats.

Abstract

BACKGROUND:

Water avoidance stress (WAS) induces a naloxone-independent visceral analgesia in male rats under non-invasive conditions of monitoring. The objective of the study was to examine the role of brain CRF signaling in acute stress-induced visceral analgesia (SIVA).

METHODS:

Adult male Sprague-Dawley rats were chronically implanted with an intracerebroventricular (ICV) cannula. The visceromotor response (VMR) to graded phasic colorectal distension (CRD: 10, 20, 40, 60 mm Hg, 20 seconds, 4 minutes intervals) was monitored using manometry. The VMR to a first CRD (baseline) was recorded 5 minutes after an ICV saline injection, followed 1 hour later by ICV injection of either CRF (30, 100, or 300 ng and 1, 3, or 5 μg/rat) or saline and a second CRD, 5 minutes later. Receptor antagonists against CRF1 /CRF2 (astressin-B, 30 μg/rat), CRF2 (astressin2 -B, 10 μg/rat), oxytocin (tocinoic acid, 20 μg/rat), or vehicle were injected ICV 5 minutes before CRF (300 ng/rat, ICV) or 15 minutes before WAS (1 hour).

KEY RESULTS:

ICV CRF (100 and 300 ng) reduced the VMR to CRD at 60 mm Hg by -36.6% ± 6.8% and -48.7% ± 11.7%, respectively, vs baseline (P < 0.001), while other doses had no effect and IP CRF (10 µg/kg) induced visceral hyperalgesia. Astressin-B and tocinoic acid injected ICV induced hyperalgesia and prevented the analgesic effect of ICV CRF (300 ng/rat) and WAS, while astressin2 -B only blocked WAS-induced SIVA.

CONCLUSIONS & INFERENCES:

These data support a role for brain CRF signaling via CRF2 in SIVA in a model of WAS and CRD likely mediated by the activation of brain oxytocin pathway.

• Authors: Muriel Larauche, Nabila Moussaoui, Mandy Biraud, Won Ki Bae, Henri Duboc, Mulugeta Million, Yvette Taché
• Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 31 Issue 2 Pg. e13489 (02 2019) ISSN: 1365-2982 [Electronic] England
• PMID: 30298965 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• Corticotropin-Releasing Hormone

Topics

• Animals
• Brain (metabolism)
• Corticotropin-Releasing Hormone (metabolism)
• Hyperalgesia (physiopathology)
• Male
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Stress, Psychological (physiopathology)
• Visceral Pain (physiopathology)