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Pain and osteoarthritis: new drugs and mechanisms

Purpose of review This review discusses the recent literature on drugs used for symptomatic pain relief in patients with osteoarthritis (OA) as well as potential mechanisms underlying their pharmacologic action. Recent findings Recent research has shed light on the molecular mechanisms underlying the contribution of prostaglandins to pain sensation. Moreover, the role of the enzymes cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) in inflammation and subsequent structural changes of joints has been clarified. Based on the COX-1/COX-2 hypothesis, various selective COX-2 inhibitors with improved gastrointestinal tolerability as compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have been established for the symptomatic treatment of OA in recent years. Rational therapy with these compounds should be based on their diverse pharmacokinetic characteristics. Among the traditional NSAIDs, the mode of action of aceclofenac has been recently clarified in that the compound was shown to elicit preferential inhibition of COX-2 as a result of limited but sustained biotransformation to diclofenac. Novel mechanisms have also been proposed to account for the action of acetaminophen. Finally, there is evidence from animal models to suggest that the dual LOX/COX inhibitor licofelone may stop disease progression in OA. Clinical studies are under way to establish this compound for treatment of OA. Summary It is anticipated that new insights into the pathophysiology of OA as well as novel therapeutics will improve the pharmacologic options in OA.