Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice. | Imhof et al. Arthritis Research Therapy 2011 13 R97 http content 13 3 R97 RESEARCH ARTICLE Open Access Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice 11 2 2 3 1 Anne-Katja Imhof Laura Gluck Mieczyslaw Gajda Rolf Brauer Hans-Georg Schaible and Stefan Schulz Abstract Introduction Endothelins are involved in tissue inflammation pain edema and cell migration. Our genome-wide microarray analysis revealed that endothelin-1 ET-1 and endothelin-2 ET-2 showed a marked up-regulation in dorsal root ganglia during the acute phase of arthritis. We therefore examined the effects of endothelin receptor antagonists on the development of arthritis and inflammatory pain in monoarthritic mice. Methods Gene expression was examined in lumbar dorsal root ganglia two days after induction of antigen-induced arthritis AIA using mRNA microarray analysis. Effects of drug treatment were determined by repeated assessment of joint swelling pain-related behavior and histopathological manifestations during AIA. Results Daily oral administration of the mixed ETA and ETB endothelin receptor antagonist bosentan significantly attenuated knee joint swelling and inflammation to an extent that was comparable to dexamethasone. In addition bosentan reduced inflammatory mechanical hyperalgesia. Chronic bosentan administration also inhibited joint swelling and protected against inflammation and joint destruction during AIA flare-up reactions. In contrast the ETA-selective antagonist ambrisentan failed to promote any detectable antiinflammatory or antinociceptive activity. Conclusions Thus the present study reveals a pivotal role for the endothelin system in the development of arthritis and arthritic pain. We show that endothelin receptor antagonists can effectively control inflammation pain and joint destruction during the course of arthritis. Our findings suggest that the antiinflammatory and antinociceptive
