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Why don't painkillers work for people with Fibromyalgia? Research may explain why common drugs don't help

  [ 328 votes ]   [ 4 Comments ]
By University of Michigan Health System • • September 29, 2007

ANN ARBOR, Mich. Sep 27, 2007 - People who have the common chronic pain condition Fibromyalgia often report that they don’t respond to the types of medication that relieve other people’s pain. New research from the University of Michigan Health System helps to explain why that might be: Patients with Fibromyalgia were found to have reduced binding ability of a type of receptor in the brain that is the target of opioid painkiller drugs such as morphine.

The study included positron emission tomography (PET) scans of the brains of patients with Fibromyalgia, and of an equal number of sex- and age-matched people without the often-debilitating condition. Results showed that the fibromyalgia patients had reduced mu-opioid receptor (MOR) availability within regions of the brain that normally process and dampen pain signals – specifically, the nucleus accumbens, the anterior cingulate and the amygdala.

“The reduced availability of the receptor was associated with greater pain among people with fibromyalgia,” says lead author Richard E. Harris, PhD, research investigator in the Division of Rheumatology at the U-M Medical School's Department of Internal Medicine and a researcher at the U-M Chronic Pain and Fatigue Research Center.

“These findings could explain why opioids are anecdotally thought to be ineffective in people with Fibromyalgia,” he notes. The findings appear in The Journal of Neuroscience. [To read an abstract of the article, click here.] “The finding is significant because it has been difficult to determine the causes of pain in patients with Fibromyalgia, to the point that acceptance of the condition by medical practitioners has been slow.”

Opioid pain killers work by binding to opioid receptors in the brain and spinal cord. In addition to morphine, they include codeine, propoxyphene-containing medications such as Darvocet, hydrocodone-containing medications such as Vicodin, and oxycodone-containing medications such as Oxycontin.

The researchers theorize based on their findings that, with the lower availability of the MORs in three regions of the brains of people with fibromyalgia, such painkillers may not be able to bind as well to the receptors as they can in the brains of people without the condition.

Put more simply: When the painkillers cannot bind to the receptors, they cannot alleviate the patient’s pain as effectively, Harris says. The reduced availability of the receptors could result from a reduced number of opioid receptors, enhanced release of endogenous opioids (opioids, such as endorphins, that are produced naturally by the body), or both, Harris says.

The research team also found a possible link with depression. The PET scans showed that the Fibromyalgia patients with more depressive symptoms had reductions of MOR binding potential in the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.

The study subjects were 17 women with Fibromyalgia and 17 women without the condition.

The senior author of the paper was Jon-Kar Zubieta, MD, PhD, the Phil F. Jenkins Research Professor of Depression in the U-M Department of Psychiatry and a member of U-M’s Molecular and Behavioral Neuroscience Institute, Depression Center and Department of Radiology. Other authors were Daniel J. Clauw, MD; David J. Scott, PhD; Samuel A. McLean, MD, MPH; and Richard H. Gracely, PhD.

The research was supported by grants from the Department of the Army; the National Center for Research Resources, a component of the National Institutes of Health; and the NIH. Harris was supported by an NIH–National Center for Complementary and Alternative Medicine Grant. McLean was supported by an NIH grant.

Reference: "Decreased central mu-opioid receptor availability in Fibromyalgia," The Journal of Neuroscience, Sept. 12, 2007, 27(37):10000–10006. PMID: 17855614, by Harris RE, Clauw DJ, et al.

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Article Comments Post a Comment

Re: suggestions?
Posted by: limbo
Oct 3, 2007
What would be your suggestions as to meds or supplements, I'm wanting to improve my mood and fatigue. I've done a lot of work on myself to improve my mood, deal with my issue's but would really want to bump my mood up.
Reply Reply

Posted by: DiamonDie
Oct 4, 2007
Well, there are dozens of possibilities that can help, both pharmaceuticals and OTC products. I'm currently working on the English version of my book about CFS and fibromyalgia treatments which will feature over 200 different medications.

I would recommend looking into low dose naltrexone. It is cheap, safe and works for a lot of people (apparently it helps fibro a bit more often than CFS). The only culprit is that you can't take any narcotics with it (all other drugs and supplements are alright). It works particularly well with DL-phenylalanine (which is OTC and good for mood issues). If you can't take LDN, it doesn't work or your doctor doesn't want to prescribe it, a stimulating antidepressant like reboxetine, duloxetine, atomoxetine, milnacipran or bupropion would be worth a try. It could improve both mood and fatigue. I'd probably pick bupropion.

As for OTC products, 5-HTP works well for depression for many, but doesn't really tackle fatigue (except indirectly by improving sleep, if your sleep is really bad). Don't take it with Rx antidepressants without doctor's supervision! SAM-e is OTC in most countries, works well for depression and is well tolerated, but I don't think it will do much for fatigue. Rhodiola rosea is good for fatigue and depression as long as you're taking a good quality product. It is somewhat of a SNRI/SSRI in addition to immune modulating qualities, so if you can't tolerate the antidepressants be careful with it (and start out with a very low dose if you are also taking antidepressants).

Lipoic acid (preferably R lipoic acid, not alpha lipoic acid) is often great for fatigue, but not really helpful for depression - unless your mood lifts when you are able to do a bit more. It works particularly well with carnitine, which can sometimes improve the mood too. Fish oil in fairly large doses (like 4-6 capsules a day) helps many with depression. It usually doesn't relieve fatigue, but it might give a nice surprise in regards to brainfog, if you have it.

Oh, and one more suggestion. Many people with fibromyalgia are hypothyroid, which can cause both fatigue and depression (and the pain, too). Doctors don't often recognize it, as they look at supposedly normal numbers instead of listening to the patient. What is normal counts for someone else could be hypothyroid for your body. You could try to ask for a trial of thyroid supplementation.

You can email me with more questions:


OK - Now What?
Posted by: crumpton
Oct 3, 2007
This is great to find out one reason we are hurting after taking medication. This is great to know I guess, but now what? I agree with Limbo. What are the suggestions for help? Will this study enable physicians to prescribe medication or provide ideas for relief?
Reply Reply

Pain relief
Posted by: mickie378
Oct 17, 2007
Hi, In regards to your question on fybro pain and pain relief, I am a 45 year old with both fybro and CFS, I noticed with my self there are days my meds barely touch my pain but all in all i Thank God i have these options for pain control.I am a active mom with two teen boys and do lot of driving. I am also in the cleaning business for 20 years.Now i only work 3 days a week.My Drs tell me to DO NOT STOP MOVING. Know your body and rest when its tough.With a good attitude and a good nights sleep,(I also tke Paxil and Seriquil for depression and sleep) i am usually ok. If i did not have my pain meds i would barely get going in the AM. Give me a hour or so in the morning to meditate and let the meds work for you. Again DO Not Stop Moving and rest in between and you can live ok..Kathie


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