MGH researchers shed new light on how pain ki...( Researchers at Massachusetts Genera...)

Researchers at Massachusetts General Hospital have shown for the first time how a class of common pain-relieving agents called nonsteroidal anti-inflammatory drugs (NSAIDs) better known as aspirin and aspirin-like products work by acting both within the central nervous system as well as in the inflamed region around the source of pain. Until now, it was thought that the effectiveness of these drugs was related to action at the inflammation site only.

The study, published in the March 22, 2001 issue of Nature, has important implications for improving the way that pain may be treated in the future and for developing safer, more effective pain-killing medications and delivery systems.

NSAIDs reduce inflammatory pain by blocking the action of certain enzymes called cyclooxygenase (Cox) 1 and 2. Cox-1 is normally expressed in the stomach, where it protects against acid damage, and in platelets, where it is involved in clotting. Cox-2, while not normally found in the skin or joints, is produced in these sites after inflammation occurs. Cox-2 is necessary in manufacturing a chemical called prostaglandin E2 (PGE2), which increases the sensitivity of nerves to pain. Inhibition of PGE2 at the site of inflammation had been thought to account for both the anti-inflammatory and pain-killing actions of NSAIDs. This 1970s discovery, in fact, earned a Nobel Prize for John Vane of London.

In the recent study, MGH researchers Clifford Woolf, MD, PhD, director of the Neural Plasticity Research Group in the Department of Anesthesia and Critical Care, Tarek Samad, PhD, a research fellow in Anesthesia, and their colleagues, showed that even as Cox-2 is produced at the site of inflammation, it also begins to be expressed in nerve cells in many regions of the spinal cord and brain. This previously unknown centralized expression results in the production of PGE2 throughout the central nervous system.

PGE2 increases the excitability of nerve cel
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Contact: Georgia W. Peirce
gpeirce@partners.org
617-724-6423
Massachusetts General Hospital
20-Mar-2001