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The latest news on fibromyalgia syndrome and chronic fatigue syndrome is posted below in support of Fibromyalgia Network's mission to educate patients and the media with ad-free reporting.
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- Imaging the Effects of Savella - June 30, 2009
- Even Mild Exercise Can Reduce Pain - May 29, 2009
- Naltrexone Offers Novel Approach to Pain Relief - April 29, 2009
- No Power to Your Punch? - March 31, 2009
Imaging the Effects of Savella
Posted: June 30, 2009
The pain inhibitory system is the suspected area where Savella (milnacipran) works to reduce pain in people with fibromyalgia. A companion study showed that fibromyalgia patients have decreased activity in the brain regions believed to be involved in the pain inhibitory system, such as the thalamus and the anterior cingulate cortex.1 So when pain signals enter the spinal cord, the brain areas that should be actively releasing pain-fighters, such as opioids, serotonin and norepinephrine, actually become less active. This is the opposite of what happens in people without pain and provides an objective basis for why fibromyalgia patients hurt all over.
Savella increases the amount of norepinephrine and serotonin at the nerve junctions in the central nervous system, which theoretically should boost the activity of the pain inhibitory system. In turn, this should raise a fibromyalgia patient's pain threshold. Using functional MRI (fMRI), Yves Mainguy, Ph.D., of France, evaluated a small group of fibromyalgia patients before and after a nine-week trial who took either Savella (100 mg twice daily) or placebo.2 He measured their pressure pain threshold at the thumbnail and their fMRI to a subjectively determined pressure pain rating of 5 on a scale of 0 to 10. The pressure required was determined for each individual in the study at week nine, just before the end of the blinded, placebo-controlled trial.
Patients responding with a greater than a 30 percent reduction in subjective pain ratings over the treatment period were defined as pain responders (this group included mostly patients taking Savella but also some placebo responders as well). However, these two groups were easily differentiated. The patients on the active drug (i.e., Savella) were found to have a significant increase in pressure pain threshold when the stimulus was applied to the thumbnail, but this was not the case for the placebo responders. Mainguy notes that "the mechanism of drug response appears to be different from that of placebo response, indicating a true pharmacological effect of the drug."
What about fibromyalgia patients who took Savella but did not reap any improvements? The non-responders to the drug typically had their symptoms for twice as long as the Savella responder group. In addition, patients who did not respond to this drug also did not display a significant improvement in pressure pain threshold.
A random subgroup of fibromyalgia patients in the trial underwent fMRI while a pressure pain stimulus was applied to their thumbnail. Those who took Savella showed significantly greater brain activity than the placebo group in the anterior cingulate cortex and a region of the brainstem ... both areas involved in the pain inhibitory control. Activity in the thalamus also increased for the patients taking Savella, but the results were not quite significant.
Mainguy states that the lower pain threshold in fibromyalgia is due to decreased activity in the brain areas controlling the spinal pain inhibitory system, and the results of the Savella study support this claim. He also comments that fMRI may be a useful tool to demonstrate the objective effects of drugs to treat fibromyalgia and provide a better understanding of how they work.
- Jensen KB, et al. Pain 144:95-100, 2009.
- Mainguy Y. Human Psychopharmacol Clin Exp 24:S19-S23, 2009.
Even Mild Exercise Can Reduce Pain
Posted: May 29, 2009
You want to exercise, but you're afraid that the amount of exercise your doctor tells you to do might throw you into a flare. On the other hand, you want to keep your strength up to continue with your daily activities and responsibilities. Besides, exercise is not only good for your heart and other muscles, but also for your self-esteem and overall well-being.
A study presented at this year's America Pain Society (APS) meeting by Dane B. Cook, Ph.D., of the University of Wisconsin, in Madison demonstrates that you might not have to work as hard as you think to benefit from an exercise program.*
Cook noted that the APS recommends moderately intense aerobic exercise two to three times a week to help manage fibromyalgia pain. But the words "aerobic" and "intense" are scary, and patients often wonder if they'll be paying the price with more pain later.
"The guidelines for a chronic pain management exercise training program may be considered unmanageable or too intense for some fibromyalgia patients," says Cook. "Research suggests that adherence rates to high-intensity exercise are lower compared to low-intensity exercise programs."
For the study, 21 women with fibromyalgia (averaging 44 years of age) rode a stationary bike for 20 minutes on two separate occasions, each at a different level of intensity. Before and after the rides, all of the women were asked to rate their pain and their pain threshold levels were measured.
In one of the sessions, the women were allowed to ride the bike however hard they wanted. They could decrease or increase the pedal resistance (ease of pedaling) of the ride as long as they maintained the preset cycling speed.
On the other bike ride, the women were required to exert a "prescribed" amount of energy that maintained their heart rate at an predetermined intensity for the individual based on their maximum heart rate, weight, age, etc. In other words, the pedal resistance made them work harder (like going uphill) to maintain the preset speed over the 20-minute workout.
Every five minutes during the tests, all the women recorded how much they felt they were exerting themselves and how much muscle pain they were experiencing. In addition, the researchers kept track of their heart rate and the amount of energy they expended.
Needless to say, when the women were riding the bike at their chosen level of intensity they felt like it was easier, they actually recorded using less energy, and their heart rates also were lower than when they rode at the required settings. Overall, the women preferred the lower-intensity ride compared to the prescribed ride.
Surprisingly, the amount of muscle pain experienced by the women was significantly lower during and after both style rides, even up to four days. So it really didn't matter how hard the women rode the bike, because even the easier, self-paced exercise was equally effective at reducing the pain.
While these results are somewhat contrary to previous findings, Cook says, "The preferred exertion (self-paced) model could be promoted as an appropriate and more generalized strategy to reduce pain in patients with fibromyalgia, especially since the pain and other debilitating symptoms are highly variable."
* Newcomb L, et al. J Pain 10(4):S16, Abstract 163, 2009.
Naltrexone Offers Novel Approach to Pain Relief
Posted: April 29, 2009
Why do many medications prescribed to treat fibromyalgia offer limited benefits? The answer may have something to do with the cells that the drugs target. All meds designed to treat pain, sleep, fatigue and cognition work by altering the chemical transmissions between one neuron and the next. But other cells, called microglia, work right along side your neurons and are capable of drastically altering the way your neurons function. What if your fibromyalgia symptoms are produced by microglial cells that have gotten out of control and are raising a ruckus in your nervous system?
This possibility was put to a preliminary test by Jarred Younger, Ph.D. and Sean Mackey, M.D., Ph.D., of Stanford University, who used low nightly doses of naltrexone in a small trial of ten fibromyalgia patients.* Naltrexone is commonly used at 10 to 20 times the dose to reduce drug cravings in addicts, but at high doses it also interferes with the body’s ability to fight pain. Yet in small quantities, naltrexone should not have much effect on pain relief, but it can quiet down microglial cells that could be at the root of your pain and possibly your other symptoms as well.
Six out of ten fibromyalgia patients in the study achieved greater than a 30 percent reduction in pain. It took about a month to achieve the maximum benefits from the drug. In fact, one 39-year-old woman who had been couch-bound went back to work as an interior decorator after the naltrexone reduced her fibromyalgia pain by more than 40 percent. Daytime fatigue was also relieved.
A trial of ten patients is small, and caution needs to be used when interpreting the results. However, if you are wondering if 4.5 mg per night of naltrexone might work for you, it may depend upon your erythrocyte sedimentation rate (ESR), a blood test used as a general marker of inflammation. Those patients who had the best response to naltrexone also had a slightly elevated erythrocyte sedimentation rate (ESR). The four patients who had low or normal ESRs did not appear to respond to the drug (e.g., their ESR was 20 mm/hr or less).
The American Fibromyalgia Syndrome Association (AFSA) funded Younger and Mackey over a year ago to conduct a blinded, placebo-controlled trial with 40 fibromyalgia patients. Each patient is serving as her own control in a crossover design study (they get a placebo for eight weeks and naltrexone for eight weeks in a blinded fashion). To validate the patient response with objective testing, pain thresholds will be measured every two weeks.
Low dose naltrexone (4.5 mg) may occasionally cause vivid dreams for the first few nights, but may be eased by backing down on the dose. For the most part, the drug is benign in terms of side effects. Naltrexone does have to be specially compounded in the low dose. The lowest commercially available dose is 50 mg. The monthly cost of compounded naltrexone is $40, and is inexpensive because its drug patent expired long ago.
The decision to try naltrexone is entirely up to you and your doctor. If you are relying upon an opioid for pain relief (even mild formulas such as tramadol), naltrexone will interfere with the opioid’s ability to treat your pain. People with low ESRs may not be good candidates for naltrexone, but if you do decide to test this novel form of treatment, be prepared to give it at least four weeks before you decide if it is working for you. The Fibromyalgia Network will report the results of the larger study as it becomes available.
* Younger J, Mackey S. Pain Medicine April 2009.
No Power to Your Punch?
Posted: March 31, 2009
Why do your muscles feel weak yet they appear normal when examined? Could it be that you just don't get enough quality sleep to revitalize your body each night? Or, is there something going on within the muscles and other cells of people with fibromyalgia that leaves you in a constant state of exhaustion? Although sleep is likely to be an important factor, Placido Navas, Ph.D., a biochemist in Spain, has identified an enzyme abnormality that might shed light on your energy drain.1
Coenzyme Q10 is produced by the mitochondria inside your cells and is a key enzyme for producing the energy required by each cell. In other words, coenzyme Q10 (CoQ10) is essential for powering up your muscles and giving you that "get-up-and-go" feeling. CoQ10 also neutralizes toxic substances or nasty waste products that may damage your cells, potentially producing pain. In addition, CoQ10 can be transported outside the cells into your plasma (the nutrient-rich liquid portion of your blood) to neutralize toxic substances. These nasty chemicals can be measured and their total quantity is often referred to as the reactive oxygen species (ROS) content.
Given that fatigue and muscle pain are primary symptoms of fibromyalgia, Navas reasoned that patients might have some abnormality with their CoQ10. Blood was drawn from 40 fibromyalgia patients for measuring CoQ10 and ROS, and the results were compared to 30 healthy control subjects (matched for age and gender). Keep in mind that the blood cell findings tend to mimic what is happening in the muscles.
Looking at the level of CoQ10 inside the cells and outside the cells in the plasma fraction of the blood, Navas made two interesting observations:
- the cell content of CoQ10 in the fibromyalgia group was 40 percent less than that of the control group
- the amount of CoQ10 in the plasma of fibromyalgia patients was double that of the healthy controls
Despite the high enzyme content in the plasma, the concentration of ROS was substantially higher in the patient group.
At first it may seem odd that patients have an abundance of CoQ10 in their plasma (the liquid portion of their blood) and an inadequate amount in their blood cells. However, Navas confirmed this imbalance by another method. The blood cells were isolated in a dish and the ROS content within them was measured. The ROS of the fibromyalgia group was significantly higher compared to the controls. Then CoQ10 was added to the dishes of isolated blood cells. Those from the fibromyalgia group sucked up the enzyme and the ROS content dropped to the level of the control group. This experiment demonstrated that the cells are deficient in CoQ10 and offers at least one explanation for why your muscles have no power to their punch.
"There is a contradictory situation in these patients," says Navas, referring to people with fibromyalgia. "Clearly the cells need more CoQ10, but the high content in the plasma is not working." What could this possibly mean? CoQ10 should be able to travel back and forth across the cell membrane so that it can be where it is most needed. Yet, there is an imbalanced distribution with too much CoQ10 in the plasma and a serious deficiency within the cells. As a result, your cells, (particularly those in your muscles) cannot produce the energy that they need to power up your body's activities.
Referring to the accumulation of CoQ10 in the plasma, Navas offers an analogy. "The picture is similar to that observed in patients with CoQ10 deficiency syndrome treated with CoQ10. If the enzyme is dissolved in oil before administering, the levels in the plasma are normal, the cells properly incorporate it, and the muscle pain/fatigue symptoms decrease significantly. However, if CoQ10 is provided as a powder, the plasma content becomes very high and no benefits are observed." The ability of CoQ10 to travel across the cell membrane depends upon the presence of fat-containing carrier molecules in the plasma.
It's possible that the carrier molecules in the plasma are defective or that CoQ10 is somehow tied up with another molecule that renders it useless. There are also multiple reports in the literature of genetic glitches that can alter the way CoQ10 functions in the body, producing a variety of symptoms such as fatigue, muscle pain, shortness of breath, gastrointestinal problems, etc.2 Navas plans to study the chemical condition of CoQ10 in the plasma and skin cells of fibromyalgia patients to gain a better understanding of why the enzyme imbalance exists and how it can be corrected.
In the meantime, you should know that the more a person exercises, the more mitochondria their cells make. An increase in the number of mitochondria per cell could possibly raise the CoQ10 level within your cells and this might be one of many ways in which gentle, aerobic exercise improves physical function in people with fibromyalgia.3 Studies have also shown that the best way to ease into a fitness program is to begin with a warm water exercise routine because you are less likely to strain your muscles.4 Take advantage of the warmer climate ahead so that you do not shiver and cramp your muscles the instant you get out of a heated pool.
Navas' research may also help explain why beginning or restarting an exercise program is so difficult. The initial activity may further drain your cells of CoQ10 and energy, but once you make more mitochondria, you may slowly start to feel better. Of course, the moment you stop exercising for any reason (such as a bad cold), your muscles may decondition rapidly, so you may not be able to pick up where you left off.
As an aside, medications that lower cholesterol, called statins, also reduce the availability of CoQ10. Based on Navas’ findings, fibromyalgia patients may be more susceptible to the muscle-pain enhancing side effects of statins and will need to discuss alternative therapies with their doctor.
- Cordero MD, et al. Clin Biochem Dec 25 [Epub ahead of print] 2008.
- Quinzii CM, et al. FASEB J 22:1874-1885, 2008.
- de Andrade SC, et al. Rheumatol Int 29:147-52, 2008.
- Evcik D, et al. Rheumatol Int 29:885-90, 2008.
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