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Omega-3 DHA Derivative May Replace Opiates
A natural derivative of DHA relieved rats’ nerve pain dramatically with no adverse effects 08/01/2013 By Craig Weatherby
Opium alleviates pain better than most drugs.

But its effectiveness wears off over time and adverse effects abound ... including addiction, which yields its own anguish.

Many millions of Americans in pain take the similar, synthetic drugs called opiates … such as oxycodone, hydrocodone, oxycontin, fentynal, and vicodin.

Opiates attach to receptors in nerve cells and change the brain's perception of pain.

Sadly, they only work temporarily for chronic pain, and typically cause one or more of many adverse effects:
  • Nausea
  • Addiction
  • Confusion
  • Drowsiness
  • Constipation
  • Urinary retention
  • Itching sensations
  • Difficulty breathing
  • Sexual dysfunction
  • Low blood pressure
  • Increasing insensitivity to opiates
Opiates affect seniors and children more than adults, making them more vulnerable to side effects.
Fast, high-dose opiates hold the potential for lasting relief
Last year, researchers reported that in rats, very high doses of a morphine-like opiate (remifentanil) “reset” the nerve signals triggered by continuous pain (Drdla-Schutting R et al. 2012).
The fast, high-dose approach also appeared to help protect and repair injured nerve tissue.

To be sure, the omega-3-derived agent discussed in our main story appears to be an even better alternative … assuming either alternative is proven to work as well in people as they do in rodents.
But like the promising DHA-derived agent, the new way of using opiates should be tried (carefully) in people, because it could be uniquely effective in some circumstances.
Two high doses given one hour apart eliminated the rats' pain permanently … while using half the dose didn't work.

If confirmed in human studies, this method could reduce or eliminate agony for millions and save the nation billions spent annually on pain drugs.
The effective dose was two to four times higher than used for normal pain control.

In fact, the animals almost stopped breathing ... which explains why this wasn't tried in people.

However, an equivalent human dose of the opiate would fall well below the proven-fatal level.

Physicians often prescribe low opiate doses and slowly raise them until adequate relief is reached.
(See our sidebar, “Fast, high-dose opiates hold the potential for lasting relief”, about a possibly more effective use of opiates.)

Medical science has long looked for more effective alternative to opiates … ones that would be much safer, too.

Evidence exists that a natural compound the body makes from omega-3 DHA holds the potential to alleviate pain and inflammation alike.

Omega-3s' anti-inflammatory secret
Omega-3 DHA is essential to human life, and occurs in every cell in the body.

Seafood and algae are the only abundant food sources of DHA, and fish oil is the richest source.

The body can make the other essential omega-3 fatty acid – EPA, which also abounds only in fish and fish oil – from DHA.

Several years ago, a team led by the renowned researcher Charles Serhan, M.D., discovered potent inflammation-ending compounds called “resolvins”, which the body makes from omega-3 EPA and DHA.

The body uses resolvins to end (“resolve”) inflammation, which is part of its own immune-system response to injuries and infections.

It also uses a compound called neuroprotectin D1 (NPD1) to end inflammation … as well as to protect nerve cells (hence its name). 

People's white blood cells make NPD1 from omega-3 DHA, in response to signals from the immune system.

This probably explains much of the proven inflammation-moderating effect of consuming DHA, either from fish or fish oil.

As we reported last March, Dr. Sherhan's team discovered that aspirin triggers production of a previously unknown resolvin that the body makes from omega-3 DHA … see “Aspirin Mimics a Fishy Omega-3”.

Now, a joint Duke-Harvard study in rodents – co-authored by Dr. Serhan – reveals that NPD1 soothed and prevented damaging nerve pain caused by surgical-type injuries (Xu ZZ et al. 2013).

Study leader Ru-Rong Ji, Ph.D., underscored one reason for their study:
“Chronic pain resulting from major medical procedures such as amputation, chest and breast surgery is a serious problem.” (DU 2013)

We hope the positive results seen in rodents mean that physicians and patients soon get access to a safer – and more effective – alternative to opiates and other problematic drugs for pain.

DHA derivative eased nerve pain in rats
NPD1 was first identified as an agent able to quickly resolve abdominal and brain inflammation.

Dr. Ji noted that NPD1 and similar compounds “are derived from omega-3 fatty acids found in fish oil, but are 1,000 times more potent than their precursors in reducing inflammation.” (DU 2013)

The team subjected mice to injuries that produce pain symptoms like those associated with post-surgical nerve trauma.

They then treated the animals with NPD1 – either by topical application to the injured area or by injection into the spinal canal – to see whether it could relieve the rodent's pain.

Encouragingly, the omega-3-derived agent greatly alleviated the animals' pain and reduced their nerve swelling following the injuries.

NPD1's analgesic effect stems from its ability to retard the release of immune system messengers (cytokines and chemokines) known to trigger and maintain inflammation.

By preventing this pro-inflammatory cascade, ND1 protected nerve cells from further damage and greatly reduced nerve pain. NPD1 relieves nerve pain at very low doses … without any apparent risk of addiction or for increasing insensitivity to this DHA derivative.

“We hope to test this compound in clinical trials,” Ji said. “DHA is very inexpensive, and can be converted to NPD1 by an aspirin-triggered pathway.” (DU 2013) 

Their research was supported by National Institutes of Health.

  • Drdla-Schutting R, Benrath J, Wunderbaldinger G, Sandkühler J. Science 335, 235–238 (2012).Frood A. Nature News. High-dose opiates could crack chronic pain. January 12, 2012. Accessed at
  • Ji RR, Xu ZZ, Strichartz G, Serhan CN. Emerging roles of resolvins in the resolution of inflammation and pain. Trends Neurosci. 2011 Nov;34(11):599-609. doi: 10.1016/j.tins.2011.08.005. Epub 2011 Sep
  • Xu ZZ, Ji RR. Resolvins are potent analgesics for arthritic pain. Br J Pharmacol. 2011 Sep;164(2):274-7. doi: 10.1111/j.1476-5381.2011.01348.x
  • Xu ZZ, Liu XJ, Berta T, Park CK, Lü N, Serhan CN, Ji RR. Neuroprotectin/Protectin D1 protects neuropathic pain in mice after nerve trauma. Ann Neurol. 2013 May 18. doi: 10.1002/ana.23928. [Epub ahead of print]
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