"There clearly is a major central nervous system component in the way that the body responds to inflammation and this has a key role in the production of pain," says Woolf. "Now that we are starting to understand how local inflammation acts centrally, we need to go down a parallel track and find ways to manage pain hypersensitivity more effectively."
In the study, Woolf and his team also shed light on the complex pathway from inflammation to pain. The journey begins when peripheral inflammation stimulates production of a molecule called interleukin 1 beta (IL-1b). IL-1b acts as the trigger that signals nerve cells to switch on the Cox-2 gene. This expression of Cox-2 in turn causes the production of PGE2, which excites nerve cells and leads to pain.
Researchers determined that this chain of events could be interrupted at several points along the way to limit the sensation of pain. Drugs targeted at blocking production of IL-1b by inhibiting IL-1b-converting enzymes or ICE, as well as agents that inhibit Cox-2 expression can break this cycle and provide effective pain relief. The researchers also found that because of the central nervous system involvement, drugs delivered directly into the spinal cord required significantly lower doses than drugs administered systemically.
Finally, the research team reported that data from the study indicate that the widespread presence of Cox-2 in the central nervous system may help address the question of why symptoms such as aches and pains, appetite loss and depression are often associated with infection and inflammation.
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Contact: Georgia W. Peirce
gpeirce@partners.org
617-724-6423
Massachusetts General Hospital
20-Mar-2001