Anti-Inflammatory Effect of the Endocannabinoid Anandamide in Experimental Periodontitis and Stress in the Rat

Abstract

Periodontitis is an infectious disease leading to inflammation and destruction of tissue surrounding and supporting the tooth. The progress of the inflammatory response depends on host immune system and risk factors such as stress. The aim of the present study was to investigate the role of the endocannabinoid anandamide in experimental periodontitis with restraint stress; since the endocannabinoid system is known to modulate the hypothalamo-pituitary-adrenal axis as well as immune functions and has been found in human gingival tissues. A rat model for experimental periodontitis (P) induced by ligature around first inferior molars and immobilization stress (S) for 2 hs twice a day during 7 days was used. Corticosterone plasma levels, locomotor activity, adrenal gland weight and bone loss were increased in P and S groups and also there was less weight gain. The inflammatory parameters such as PGE2 (RIA), Nitric Oxide (Radioconversion of 14C-Arginine), TNF alpha (ELISA) and IL-1 beta (Western blot) measured in the gingival tissue were significantly increased in the P groups as compared to control group. The local injection of anandamide (10-8M, 30µl) decreased corticosterone plasma levels and the content of the cytokines TNF alpha and IL-1 beta in gingival tissues in P plus S groups. These anandamide-induced inhibitions were mediated by CB1 and CB2 cannabinoid receptors since the injection of both antagonists together, AM251 (10-6 M) and AM630 (10-6 M), in 30µl, prevented those effects. In conclusion, the endocannabinoid anandamide diminishes the inflammatory response in periodontitis even during a stressfull situation.