COX is a major enzyme involved in the metabolism of arachidonic acid. This metabolism gives rise to the eicosanoids (leukotrienes, thromboxanes, prostacyclins, and prostaglandins). These chemicals reduce the C fiber threshold and thus sensitize them to other pain-producing chemicals and stimuli. Inhibition of COX by nonsteroidal anti-inflammatory drugs (NSAIDs) prevent such sensitization and contribute to pain relief.

There are two varieties of this enzyme in the human body:
- COX1 is the constitutive enzyme normally necessary for integrity of gastric mucosa. Its inhibition can result in gastric erosions.
- COX2 is an inducible enzyme liberated in sites of inflammation; blocking it can cause pain relief. COX2 is normally present in the brain and spinal cord, and its inhibition may contribute to some of the central analgesic action of NSAIDs.

Suzuki R, Sikandar S, Dickenson AH. Nociception: basic principles. In: Bruera ED, Portenoy RK (eds) Cancer Pain Assessment and Management. Cambridge University Press. Cambridge. 2010. p. 4.