Abstract | BACKGROUND & AIMS: METHODS: Male rats were subjected to 1-hour water avoidance (WA) stress or subcutaneous corticosterone injection daily for 10 consecutive days in the presence or absence of corticoid-receptor antagonist RU-486 and cannabinoid-receptor agonist WIN55,212-2. The visceromotor response to colorectal distension was measured. Receptor protein levels were measured and whole-cell patch-clamp recordings were used to assess transient receptor potential vanilloid type 1 (TRPV1) currents in L6-S2 dorsal root ganglion (DRG) neurons. Mass spectrometry was used to measure endocannabinoid anandamide content. RESULTS: Chronic WA stress was associated with visceral hyperalgesia in response to colorectal distension, increased stool output and reciprocal changes in cannabinoid receptor 1 (CB1) (decreased) and TRPV1 (increased) receptor expression and function. Treatment of WA stressed rats with RU-486 prevented these changes. Control rats treated with serial injections of corticosterone in situ showed a significant increase in serum corticosterone associated with visceral hyperalgesia, enhanced anandamide content, increased TRPV1, and decreased CB1 receptor protein levels, which were prevented by co-treatment with RU-486. Exposure of isolated control L6-S2 DRGs in vitro to corticosterone reproduced the changes in CB1 and TRPV1 receptors observed in situ, which was prevented by co-treatment with RU-486 or WIN55,212-2. CONCLUSIONS: These results support a novel role for corticosterone to modulate CB1 and TRPV1-receptor pathways in L6-S2 DRGs in the chronic WA stressed rat, which contributes to visceral hyperalgesia observed in this model.
|
Authors | Shuangsong Hong, Gen Zheng, Xiaoyin Wu, Natasha T Snider, Chung Owyang, John W Wiley |
Journal | Gastroenterology
(Gastroenterology)
Vol. 140
Issue 2
Pg. 627-637.e4
(Feb 2011)
ISSN: 1528-0012 [Electronic] United States |
PMID | 21070780
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Benzoxazines
- Morpholines
- Naphthalenes
- Receptor, Cannabinoid, CB1
- Receptors, Glucocorticoid
- TRPV Cation Channels
- Trpv1 protein, rat
- Mifepristone
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
- Corticosterone
|
Topics |
- Animals
- Benzoxazines
(pharmacology)
- Chronic Disease
- Colon
(drug effects, metabolism)
- Corticosterone
(pharmacology, physiology)
- Disease Models, Animal
- Feces
- Ganglia, Spinal
(drug effects)
- Hyperalgesia
(etiology, metabolism)
- Male
- Mifepristone
(pharmacology)
- Morpholines
(pharmacology)
- Naphthalenes
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Cannabinoid, CB1
(analysis, metabolism)
- Receptors, Glucocorticoid
(antagonists & inhibitors)
- Sensory Receptor Cells
(chemistry, drug effects, metabolism)
- Stress, Psychological
(complications, metabolism)
- TRPV Cation Channels
(analysis, metabolism)
|