For release: Friday, September 17, 2010
Chronic inflammatory pain is among the most common health problems and the most difficult to treat. New research points to molecules called resolvins as a possible alternative treatment for inflammatory pain when other drugs prove inadequate.
Inflammation – sometimes visible as swelling and redness – can cause pressure on sensitive nerve endings, which produces pain.
Available treatments for inflammatory pain include opioids, such as morphine, and non-steroid anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen. These are potent painkillers, but they can cause troubling side effects when used for chronic pain. Over the long-term, opioid use is associated with addiction and blunting of normal (non-painful) sensations. Meanwhile, the newest NSAIDs, called COX-2 inhibitors, may increase the risk of heart attack and stroke.
Another problem with many painkillers is that they block natural processes in the body that help bring inflammation to an end, instead of just blocking inflammation. Resolvins – small molecules derived from the omega-3 fatty acids found in fish – are known to help resolve inflammation. But until now their role in inflammatory pain had not been explored.
A new study in Nature Medicine* shows that, in mice, injections of the resolvins RvE1 and RvD1 can alleviate inflammatory pain caused by tissue injury, nerve damage or chemical irritants such as capsaicin, the active ingredient in chili peppers. The work was funded in part by an NIH transformative R01 grant, as well as by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Dental and Craniofacial Research (NIDCR).
The research was led by Ru-Rong Ji, Ph.D., an associate professor of anesthesiology at Brigham and Women's Hospital and Harvard Medical School in Boston, and Charles Serhan, Ph.D., a professor of anesthesiology at Harvard Medical School who discovered resolvins.
The team found that RvE1 was effective at a dose 10,000 times lower than its parent omega-3 fatty acid compounds. It was also 1,000 to 10,000 times more potent than morphine or a commonly studied COX-2 inhibitor.
The team discovered that RvE1 does more than reduce the inflammation that causes pain. RvE1 also affects the way that pain-sensing nerve cells in the spinal cord respond to inflammation, an effect that could make them especially effective against chronic pain.
“We know that the transition from acute pain to chronic pain involves changes in the nervous system, but we don’t know how to stop or reverse these changes. This study is innovative in that it shows resolvins may be able to suppress cellular activity in the spinal cord that leads to chronic pain,” said Linda Porter, Ph.D., a program director at NINDS.
The study also shows that RvE1 acts through two mechanisms in the spinal cord. The compounds work partly by blocking the function of TRPV1, a receptor for capsaicin found in pain-sensing neurons. They also block the function of the NMDA-type receptor for the brain chemical glutamate. The NMDA receptor is known to contribute to the transition from acute to chronic pain, strengthening the idea that resolvins might prevent this transition.
“The data look very promising, and we are hopeful that future studies will show resolvins to be effective for pain relief in humans,” Dr. Porter said.
- By Daniel Stimson, Ph.D.
*Xu Z-Z et al. “Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions.” Nature Medicine, Vol. 16(5), May 2010, pp. 592-597.
Image: TRPV1 (green) and ChemR23 (red), a receptor for RvE1, are found together in sensory neurons.
Last Modified December 24, 2013