There is evidence of effects of morphine on cell proliferation and intraarticular morphine produces analgesia and has an anti-inflammatory effect in chronic arthritis. The effects of opioids are mediated through the G-protein-coupled receptors affecting the cAMP pathway. We demonstrated that human osteoarthritic cartilage and cultured chondrocytes possess the beta-opioid receptor. The presence of the receptor was shown by immunodetection, polymerase chain reaction, and Western blotting. Stimulation of chondrocytes with beta-endorphin resulted in decreased phosphorylation of the transcription factor cAMP responsive element binding protein (CREB). The effect was reversed by naltrexone. The obtained results indicate that in human articular chondrocytes opioids affect, via the mu-opioid receptor, the transcription factor CREB which in turn can cause subsequent changes in gene expression. (C) 2003 Elsevier Inc. All rights reserved.