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Corticosterone mediates reciprocal changes in CB 1 and TRPV1 receptors in primary sensory neurons in the chronically stressed rat.

AbstractBACKGROUND & AIMS:
Chronic stress is associated with visceral hyperalgesia in functional gastrointestinal disorders. We investigated whether corticosterone plays a role in chronic psychological stress-induced visceral hyperalgesia.
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.
AuthorsShuangsong Hong, Gen Zheng, Xiaoyin Wu, Natasha T Snider, Chung Owyang, John W Wiley
JournalGastroenterology (Gastroenterology) Vol. 140 Issue 2 Pg. 627-637.e4 (Feb 2011) ISSN: 1528-0012 [Electronic] United States
PMID21070780 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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)

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