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New Therapies Inhibit COX-2 Enzyme, Help Relieve Pain

  [ 73 votes ]   [ Discuss This Article ] • April 9, 2003

Pain is an unfortunate and unwelcome symptom of many chronic illnesses, but scientific research has pinpointed a single enzyme in the body called COX-2 that plays a pivotal role in the way we experience pain. This research has led to the development of new and advanced therapies that inhibit COX-2, helping to bring relief to chronic pain sufferers.

What is COX?

COX is an abbreviation for the natural enzyme cyclooxygenase. There are two forms of this enzyme in the body, COX-1 and COX-2:

--COX-1 is produced throughout the body and helps manage day-to-day cellular and metabolic activities, including maintaining the health of stomach lining, regulating blood flow to the kidneys and balancing platelet function.

--COX-2 is important to initiating the pain response and is only present in the body on a limited basis; however dietary factors such as stress and injury can increase COX-2 production.

How Does COX Work?

Cell membranes of all types contain a fatty acid called arachadonic acid. As old cells die off and new cells replace them, arachadonic acid is released into the blood stream. Both the COX-1 and COX-2 enzymes react when they come into contact with the acid and form compounds called prostaglandins. These are molecules that produce a variety of hormone like actions in the body. The prostaglandins produced by the COX-1 enzyme are important to maintaining mucous production in the stomach, which protects the stomach lining from harsh digestive acids.

When the COX-2 enzyme comes into contact with arachadonic acid, it produces pro-inflammatory prostaglandins, which cause the stiffness, swelling and pain that accompanies an illness or injury. COX-2’s function in the pain process has lead researchers to develop therapies that target the enzyme and relieve pain.

COX-2 Inhibitors

Many over-the-counter pain relievers such as aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) that are generally the first line of defense against pain, inhibit both COX-1 and COX-2 enzymes. After prolonged use, and long term inhibition of COX-1, some NSAIDs can prevent prostaglandins from maintaining healthy levels of mucous in the stomach, which in turn may lead to side effects such as gastrointestinal irritation, and even serious complications such as ulcers and gastrointestinal bleeding. These complications prompted the development of new therapies that inhibit only the COX-2 enzyme, sparing COX-1 and preserving the health of the stomach.

COX-2 inhibitors are designed to attack the pathological production of pro-inflammatory prostaglandins. Many of these therapies have been developed to be highly selective in inhibiting only the COX-2 enzyme. With a low level of COX-2 in the body the production of pro-inflammatory prostaglandins is reduced, thereby helping to limit symptoms of pain, stiffness and inflammation. Many new therapies, including natural and herbal therapies, have been developed to selectively reduce the presence of COX-2 while avoiding harmfully low levels of COX-1.

There are many natural sources of COX-2 inhibitors. For example, a compound called resveratrol, a chemoprotective agent found in grapes as well as the eastern root Hu Zhang, was investigated as a COX-2 inhibitor by researchers at Cornell.(1) By exposing human mammary and oral epithelial cells to phorbol esters, COX-2 expression was induced as well as the synthesis of pro-inflammatory prostaglandins. The administration of resveratrol inhibited these effects as well as the direct activity of COX-2.


1. Subbaramaiah K, Michaluart P, Chung WJ, Tanabe T, Telang N, Dannenberg AJ. “Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells.” Ann N Y Acad Sci. 1999;889:214-23.

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