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Corticosterone mediates reciprocal changes in CB 1 and TRPV1 receptors in primary sensory neurons in the chronically stressed rat Hong S; Zheng G; Wu X; Snider NT; Owyang C; Wiley JWGastroenterology 2011[Feb]; 140 (2): 627-637.e4BACKGROUND & 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.|Animals[MESH]|Benzoxazines/pharmacology[MESH]|Chronic Disease[MESH]|Colon/drug effects/metabolism[MESH]|Corticosterone/pharmacology/*physiology[MESH]|Disease Models, Animal[MESH]|Feces[MESH]|Ganglia, Spinal/drug effects[MESH]|Hyperalgesia/etiology/*metabolism[MESH]|Male[MESH]|Mifepristone/pharmacology[MESH]|Morpholines/pharmacology[MESH]|Naphthalenes/pharmacology[MESH]|Rats[MESH]|Rats, Sprague-Dawley[MESH]|Receptor, Cannabinoid, CB1/analysis/*metabolism[MESH]|Receptors, Glucocorticoid/antagonists & inhibitors[MESH]|Sensory Receptor Cells/chemistry/*drug effects/metabolism[MESH]|Stress, Psychological/*complications/metabolism[MESH]|TRPV Cation Channels/analysis/*metabolism[MESH] |
