Pharmacology of cyclooxygenase-2 inhibitors and preemptive analgesia in acute pain management

PURPOSE OF REVIEW: NSAIDs have served as analgesic, antiinflammatory, and antipyretic medicines for over a century. A novel class of NSAIDs, cyclooxygenase-2 inhibitors, was introduced in 1999. All NSAIDs and aspirin inhibit active sites of cyclooxygenase-1 and cyclooxygenase-2. Recent studies have demonstrated an important role of cyclooxygenase-2 inhibitors in the management of acute pain processes. RECENT FINDINGS: There have been many reports related to an 'imbalance theory' suggesting that cyclooxygenase-2 inhibitors create an 'imbalance' between thromboxane and prostacyclin (reduction of prostacyclin), resulting in a prothrombic state; however, these drugs were designed to have improved gastrointestinal safety profiles by being more selective of the cyclooxygenase-2 pathway. Although balance and regulation of hemostasis is influenced in part by the balance of prostacyclin and thromboxane A2, many other substances are involved in thrombosis and include the coagulation cascade, fibrinogen and plasminogen pathways, numerous endogenous substances such as adenosine, nitric oxide, and serotonin. SUMMARY: On the basis of many human studies, one may conclude that perioperative cyclooxygenase-2 inhibitors, in standard doses, decrease opioid consumption. Future investigations that include different multimodal techniques, for example combining cyclooxygenase-2 inhibitors with regional blocks, may help elucidate and clarify the true benefits of perioperative cyclooxygenase-2 inhibitors in acute pain management strategies.