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Pain May be Relieved by Omega-3 Byproducts
6/7/2010
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Study in mice suggests that omega-3s from fish could ease pain… and form the basis of a safer new class of potent analgesic drugs
by Craig Weatherby


Non-prescription analgesic drugs like aspirin and ibuprofen make life more bearable for millions of people suffering from all sorts of pain.

But these so-called “non-steroidal anti-inflammatory drugs”
NSAIDs for shortcome with serious side effects that kill or injure thousands of Americans every year.

Key Points
  • Mouse study shows that resolvins—compounds the body produces from omega-3s—possess powerful pain-reducing properties.
  • Omega-3-dreived resolvins could present a safer new class of analgesic drugs.
  • Fish oil cannot produce quick, noticeable pain relief, but the new findings suggest that diets rich in omega-3s may help blunt pain over time.
Estimates of the annual deaths in the United States attributable to NSAIDs vary from 3,200 to higher than 16,500 (Cryer B 2005; Lanas A et al. 2005).

And among elderly Americans alone, there are an estimated 41,000 hospitalizations related to NSAIDs each year (Griffin MR 1998).

Current NSAIDs alleviate pain and inflammation by blocking the action of one or both of two cyclooxygenase (COX) type enzymes… either the COX-1 enzyme and/or the COX-2 enzyme, depending on the drug.

The COX-1 enzyme promotes inflammation, but drugs
 such as aspirin, ibuprofen (e.g., Advil), and naproxen (e.g., Aleve) that block it can produce gastric bleeding, duodenal ulcers, kidney problems, and cardiovascular complications.

Scientists developed COX-2 drugs such as Celebrex and Vioxx to get around the adverse gastric effects of COX-1 drugs… but it turned out that they, too, can cause gastric injury.

And sharp increases in cardiovascular complications led to withdrawal of Vioxx from the market in 2004.

Clearly, it behooves the medical community to find alternative analgesics that do not work in the same way.

We’ve reported on the recent discovery that when we metabolize omega-3s from fishespecially DHAthey yield critical anti-inflammatory compounds called resolvins.

Now, the analgesic potential of omega-3-derived resolvins has gained significant support in a mouse study from the Pain Research Center at Brigham and Women's Hospital… a teaching hospital of Harvard Medical School in Boston.

Mouse study yields encouraging findings on an omega-3 fat’s analgesic potential
A research team at Brigham and Women’s Hospital reports that resolvins that the body produces from the two key omega-3s in fish fat and human cellsDHA and EPAmay serve as a new class of painkillers for treating inflammatory pain (Xu ZZ et al. 2010).

The Boston-based group believes that resolvins reduce pain both by damping inflammation and by acting in the spinal cord to prevent and reverse chronic pain.

Inflammatory pain, such as arthritic and post-operative pain, is triggered by tissue injury, leading to the release of compounds that increase inflammation and also act within the spinal cord to promote persistent pain.

The researchers found that two resolvinsRvE1 (derived from EPA) and RvD1 (derived from DHA)reduced inflammatory pain symptoms in mice.

The results showed that RvE1 was 10,000 times more potent at alleviating pain than omega-3 EPA itself, which suggests that resolvins should be targets for drug development.

Confirming the mechanism by which omega-3s can relieve pain indirectly, an artificial compound called Chemerinwhich binds to the same cell receptor as RvE1 and RvD1also significantly reduced pain symptoms.

Aside from its proven anti-inflammatory effects, they also found that RvE1 acts in the spinal cord to prevent the persistent activation of nerve cells that underlies chronic pain.

Importantlyand unlike powerful analgesic opiate-class drugs like codeine or oxycontinthe analgesic effects of the omega-3-derived resolvins did not alter the animals’ normal sensitivity to pain.

We hope that findings like these will lead to a new class of analgesic drugs that are much safer but just as effective as NSAIDs.

The study was funded by grants from the National Institutes of Health.


Sources
  • Cryer B. NSAID-associated deaths: the rise and fall of NSAID-associated GI mortality. Am J Gastroenterol. 2005 Aug;100(8):1694-5.
  • Griffin MR. Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Am J Med. 1998 Mar 30;104(3A):23S-29S; discussion 41S-42S. Review.
  • Lanas A, Perez-Aisa MA, Feu F, Ponce J, Saperas E, Santolaria S, Rodrigo L, Balanzo J, Bajador E, Almela P, Navarro JM, Carballo F, Castro M, Quintero E; Investigators of the Asociación Española de Gastroenterología (AEG). A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol. 2005 Aug;100(8):1685-93.
  • Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 1999;26(suppl):18–24.
  • Tarone RE, Blot WJ, McLaughlin JK. Nonselective nonaspirin nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding: Relative and absolute risk estimates from recent epidemiologic studies. Am J Ther 2004;11(1):17–25.
  • Tenenbaum J. The epidemiology of nonsteroidal anti-inflammatory drugs. Can J Gastroenterol. 1999 Mar;13(2):119-22. Review.
  • Xu ZZ, Zhang L, Liu T, Park JY, Berta T, Yang R, Serhan CN, Ji RR. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat Med. 2010 May;16(5):592-7, 1p following 597. Epub 2010 Apr 11.

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