Melatonin has potent antioxidant, analgesic, and antinociceptive properties. However, the effects of melatonin against oxidative stress-induced cytotoxicity and inflammatory mediators in human chondrocytes remain poorly understood. This study examined the effects and underlying mechanism of melatonin in hydrogen peroxide (H(2) O(2) )-stimulated human chondrocytes and rabbit osteoarthritis (OA) model. Melatonin markedly inhibited hydrogen peroxide (H(2) O(2) )-stimulated cytotoxicity, iNOS, and COX-2 protein and mRNA expression, as well as the downstream products, NO and PGE(2) . Incubation of cells with melatonin decreased H(2) O(2) -induced Sirtuin 1 (SIRT1) mRNA and protein expression. SIRT1 inhibition by sirtinol or Sirt1 siRNA reversed the effects of melatonin on H(2) O(2) -mediated induction of pro-inflammatory cytokines (NO, PGE(2) , TNF-α, IL-1β, and IL-8) and the expression of iNOS, COX-2, and cartilage destruction molecules. Melatonin blocked H(2) O(2) -induced phosphorylation of PI3K/Akt, p38, ERK, JNK, and MAPK, as well as activation of NF-κB, which was reversed by sirtinol and SIRT1 siRNA. In rabbit with OA, intra-articular injection of melatonin significantly reduced cartilage degradation, which was reversed by sirtinol. Taken together, this study shows that melatonin exerts cytoprotective and anti-inflammatory effects in an oxidative stress-stimulated chondrocyte model and rabbit OA model, and that the SIRT1 pathway is strongly involved in this effect.

This study was designed to evaluate the pain control effect by morphine injection to masticatory muscle pain patients. Patients with masticatory muscle pain visited the Department of Oral Medicine, Kyung Hee University Dental Hospital were recruited to this study and diagnosed by RDC/TMD. Experimental group were divided into four group; saline injection group (n=10), lidocaine injection group (n=10), morphine 1.5 mg injection group (n=10) and morphine 3 mg injection group (n=10). Evaluation list was the subjective pain evaluation(visual analogue scale, Mc Gill pain questionnaire, pain drawing) and the objective pain evaluation(pressure pain threshold, pressure pain tolerance) and evaluation time was injection before, after 1 hour, 24 hour, 48 hour and then it was analyzed statistically. The results were as follows : 1. The subjective pain evaluation were significantly different statistically in morphine 3 mg group after 48 hour. (VAS: p<0.01, MGQ: p<0.001, PD: p<0.05) 2. The objective pain evaluation were significantly different statistically in morphine 1.5 mg group after 1 hour. (PPT: p<0.01, PPTol: p<0.05) 3. The morphine 3 mg group were more significantly different than lidocaine group and morphine 1.5 mg group statistically in the McGill pain questionnaire evaluation. (1h: p<0.01, 24h: p<0.01, 48h: p<0.001) Therefore, it was revealed that the morphine 3 mg injection was effective to pain control for masticatory muscle pain patients within 48 hours and more effect than lidocaine injection.