There are approximately 4.2 million visits annually to emergency rooms for non-fatal sports and recreation related injuries in the US.¹ Sports injury leads to the release of phospholipids from cell membranes, which are converted into arachidonic acid by the action of phospholipase A₂. Arachidonic acid in turn acts as a substrate for cyclo-oxygenase (COX) resulting in the production of various prostaglandins (PGs). There are two forms of COX: COX-1 (constitutively present) and COX-2 (induced). Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit both types of COX enzymes, whereas COX-2-specific inhibitors inhibit only the COX-2 enzyme. COX-2 inhibitors were developed with the aim of reducing the incidence of serious adverse gastrointestinal effects associated with the administration of traditional NSAIDs. The assumption was that gastrointestinal side effects were COX-1-mediated. There are two major reasons for the use of NSAIDs and COX-2 inhibitors in the treatment of athletic injuries: to decrease excessive inflammation so as to increase the rate of healing, and to decrease pain associated with inflammation.

Among the PGs, PGE₂ is the predominant mediator of both peripheral and central pain sensitisation.² As the prostanoid most associated with inflammatory response, the formation of PGE₂ at an injured site is an indication of peripheral inflammation. Recently, peripheral inflammation has also been shown to induce a widespread increase in COX-2³ and PGs in the central nervous system (CNS). The proinflammatory cytokine interleukins 6 and 8 are upregulated in the CNS and play a role in inducing central PGE₂ upregulation after inflammation induced by surgical trauma. …