The Role of Peripheral Cannabinoid Receptors Type 1 in Rats With Visceral Hypersensitivity Induced by Chronic Restraint Stress.
- Author:
Lei SHEN
1
;
Xiao jun YANG
;
Wei QIAN
;
Xiao hua HOU
Author Information
1. Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Houxh@public.wh.hb.cn
- Publication Type:Original Article
- Keywords:
Irritable bowel syndrome;
Receptor, Cannabinoid, CB1;
Stress disorders;
Hyperalgesia
- MeSH:
Animals;
Blotting, Western;
Colon;
Hyperalgesia;
Hypersensitivity;
Injections, Intraperitoneal;
Irritable Bowel Syndrome;
Negotiating;
Piperidines;
Polymerase Chain Reaction;
Pyrazoles;
Rats;
Receptor, Cannabinoid, CB1;
Receptors, Cannabinoid;
Reflex;
Salicylamides;
Up-Regulation
- From:Journal of Neurogastroenterology and Motility
2010;16(3):281-290
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/AIMS: This study was designed to investigate the possibility that the enhanced nociceptive responsiveness associated with canabonoid type 1 receptors (CB1Rs) and identify its role in mediating visceral hypersensitivity induced by chronic restraint stress. METHODS: Rats were exposed to daily partial restraint stress or sham partial restraint stress with intraperitoneal injection of the vehicle, CB1R agonist or antagonist for 4 consecutive days. We tested the visceromotor reflex to colorectal distention at day 0 and 5. Reverse-transcription polymerase chain reaction and Western blot were used to assess the expression of CB1Rs. RESULTS: Intraperitoneal CB1 agonist (ACEA) injection significantly diminished (p < 0.05) the enhanced visceromotor reflex to colorectal distention at day 5 in stressed rats. Change in electromyogram response after ACEA over baseline, at pressure of 40 mmHg (+13.3 +/- 2.2), 60 mmHg (+15.3 +/- 2.8) and 80 mmHg (+17.0 +/- 4.0) were much lower than in the control animals, which were +35.9 +/- 5.1, +41.1 +/- 6.3 and +54.1 +/- 9.6, respectively. Whereas, CB1 antagonist (SR141716A) had an opposite effect. Compared with control group, the change in electromyogram response after SR141716A over baseline was significantly enhanced (p < 0.05) for the distending pressure of 40 mmHg (+56.0 +/- 10.3), 60 mmHg (+74.6 +/- 12.3) and 80 mmHg (+82.9 +/- 11.0), respectively. Reverse-transcription polymerase chain reaction and Western blotting demonstrated the stress-induced up-regulation of colon CB1Rs (p < 0.05). CONCLUSIONS: Our results suggest there is a key contribution of peripheral CB1Rs involved in the maintenance of visceral hyperalgesia after repeated restraint stress, providing a novel mechanism for development of peripheral visceral sensitization.
