[Pain of the joint of inflammatory diseases pathobiochemistry and pharmacology.].

Pain is the leading symptom of inflammatory joint diseases. It is immediately caused by the release of prostaglandins (and potentially leukotrienes) from cells of the inflamed tissues, which sensitizes the pain receptors. The synthesis of these mediators depends on the activation of infiltrated inflammatory cells, as well as recruitment of tissue born cells, predominantly by the inflammatory cytokines Interleukin-1 (IL-1) or tumor necrosis factor (TNF). In chronic diseases such as rheumatoid arthritis the inflammatory reaction is initialized and perpetuated by (auto)-immuno reactions. The associated chronic pain is thus the end point of a complex multi-level disease process. The hierarchy of these regulatory processes is mirrored by the pharmacological interventions. Inhibitors of the key enzyme of prostaglandin synthesis, cyclooxigenase, such as the non-steroidal anti-inflammatory drugs (NSAID) are immediately analgetic. Anti-inflammatory drugs as the glucocorticoids predominantly decrease the synthesis of cytokines, and thereby the stimuli leading to prostaglandin synthesis. Together with a decrease of the synthesis of arachidonate metabolizing enzymes this leads to correction of pain. Although not directly analgetic, immunosuppressive drugs, too, by decreasing the immune reaction dependent inflammation, contribute to pain relief.