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Treating pain via immune pathways: Naltrexone and Fibromyalgia
Monday 12 March 2012
It's really fascinating to watch different pieces of the fibromyalgia puzzle come together in a way that starts to make sense.
New information is available about extremely low doses of the drug naltrexone, which Stanford researchers have for the past several years been investigating as a fibromyalgia treatment. When it comes to lessening fibromyalgia pain, the drug has shown real promise in early trials, so researchers are moving forward and say they're continuing to see positive results. However, the pain-relieving effect now appears to be coming from an unexpected place, according to preliminary data presented recently at a medical conference.
Naltrexone has an effect on the brain's opioid pathways, named for the impact of opioid (narcotic) painkillers, so it seemed logical that this effect was responsible for effect on pain. However, it's now looking like that mechanism of action isn't related to how this drug helps us. Instead, scientists say, it appears to be working through the brain's own immune system instead of pain or painkilling pathways.
The Brain's Immune System
Because of the blood-brain barrier (BBB), the brain is well insulated from many of the things you find circulating around the rest of the body. Most viruses and bacteria can't get in. Most toxins can't get in. Many nutrients can't even get in, or do so in miniscule amounts. Many drugs that work on the brain need a special ingredient to help them get past the BBB.
This keeps the brain in a safe, tightly control environment. That's good. However, it also isolates the brain from the body's immune system.
Because of that, the brain needs to take care of its own immunity. The job falls to specialized cells called glia. Glial cells are the white matter of the brain and are fundamentally different from gray-matter neurons, which is what usually comes to mind when we think of brain cells.
When the brain is under attack, certain types of glial cells called microglia can cause the release of inflammatory cytokines. (Those who follow chronic fatigue syndrome research are highly familiar with those things!)
Cytokines are an important part of both the brain's and the body's immune system. They lead to inflammation, which is protective in the right circumstances. However, if cytokine levels become too high, which may happen in fibromyalgia (and chronic fatigue syndrome) inflammation can become chronic. According to a different presentation at the same medical conference, cytokines may also make neurons less receptive to pain killers.
The Stanford researchers believe that drugs such as naltrexone relieve fibromyalgia pain by changing the way microglia behave. Hypothetically, this could reduce unhealthy inflammation and also make pain killers work better for us.
Want to know more about glia? See my review of The Other Brain, by R. Douglas Fields, PhD.
Inflammation in Fibromyalgia
For a long time, doctors assumed that fibromyalgia was an inflammatory condition. After all, most painful conditions are. Then it became clear that those of us with fibromyalgia generally don't test positive for high inflammatory markers, so the thinking changed. Meanwhile, millions of us (and our doctors) wondered why we consistently had test results showing slightly high markers that medical science said were too low to worry about.
In the past year, some emerging research has brought back the theory of inflammation in us. Ginevra Liptan, MD, from Oregon Health Sciences University, has demonstrated that we may have chronic inflammation of the fascia - a thin layer of connective tissue that surrounds muscles, organs and other internal structures in a complex network stretching throughout your entire body. This could explain why our pain can be anywhere and everywhere, and why we seem to have persistent low-grade inflammation.
See my review of Dr. Liptan's book, Figuring Out Fibromyalgia.
What Does This Mean for Us?
Studies of low-dose naltrexone (LDN) for fibromyalgia are in the early stages, which means it's too soon for most doctors to be comfortable prescribing it. However, it's been on the market for a long time and is relatively cheap.
The latest preliminary data from Stanford suggest that LDN makes a significant difference in almost half of us (48.5%), and made a smaller difference in another quarter. Participants reported that it was almost as tolerable as a placebo - and for a group of folks who have trouble tolerating anything, that's a big deal! The most common side effects were headache and vivid dreams.
It's worth noting that LDN doesn't appear to help with our fatigue or sleep quality. Pain has been the primary focus of the studies thus far, so we don't know what, if any, impact it may have on our other myriad symptoms. Still, when you're constantly wracked with intense pain, pain relief is probably your primary focus, too! There's also the general tendency for lowering pain levels to help our nervous systems quiet down, thus indirectly helping alleviate other symptoms.
For researchers, this points to a new direction for pain research. Medpage Today quotes Linda Watkins, PhD, of the University of Colorado as saying, "Immunologists have ignored pain, and pain people have ignored immunology. That has to end. They are intertwined."
Have you taken LDN? How did it work for you? Have you requested it and been told no? Leave your comments here.
Learn more or join the conversation!
The above originally appeared here.
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