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Fibromyalgia Study Provides Possible Explanation for Reduced Efficacy of Opioid Therapy

Caroline Cassels

Medscape Medical News 2007. ? 2007 Medscape

October 3, 2007 ? A new study indicates individuals with fibromyalgia (FM) have decreased opioid-receptor?binding ability, a finding that may explain a long-held anecdotal observation that treatment with opiates has reduced efficacy in this patient population.

Using positron emission tomography (PET), investigators at the University of Michigan Health System found that compared with healthy, matched controls, FM patients had reduced μ-opioid-receptor (MOR)?binding potential (BP) in the nucleus accumbens, the anterior cingulate, and the amygdala, areas of the brain known to play a role in pain modulation.

"We found that patients with fibromyalgia have lower receptor availability, also known as binding potential, within 3 structures of the central nervous system. In practical terms, this may indicate that exogenous opiates would not be able to bind to these receptors and therefore would not be able to alleviate the chronic pain that is characteristic of this condition," Richard Harris, PhD, the study's first author, told Medscape Neurology & Neurosurgery.

"I think this study gives us a little more information on what, mechanistically, is going on in the central nervous system of these patients. It looks as though the opioid system [of FM patients] is dysfunctional and not operating at the same level as it does in pain-free individuals. If the opioid system is dysfunctional, clinicians may want to reconsider using opioid therapy to treat fibromyalgia patients," Dr. Harris added.

The study is published in the September 12 issue of the Journal of Neuroscience.

Possible Mechanism

According to Dr. Harris, previous research by his group has demonstrated that patients with FM and those with chronic low back pain have increased levels of endogenous opioids in their cerebral spinal fluid (CSF) compared with pain-free individuals. This result, he said, suggests that endogenous pain-management mechanisms in such individuals are activated. This would be consistent with the reduced MOR-receptor availability previously observed by Dr. Harris and colleagues.

Part of a larger, ongoing study investigating the impact of acupuncture on FM, the current study sought to determine whether the previous observation of increased levels of endogenous opioids in the CSF of FM patients was associated with decreased MOR-receptor availability, possibly through receptor downregulation.

Secondary end points included an investigation of the association of MOR availability with both the affective and sensory dimensions of clinical pain. In addition, researchers examined the relationship between depressive symptoms in FM patients and MOR BP.

For the study, 17 right-handed female FM patients were examined with PET and compared with 17 right-handed, age- and sex-matched healthy controls.

All analyses were performed using data acquired before acupuncture treatment. Patients were between the ages of 18 and 75 years and met the American College of Rheumatology criteria for the diagnosis of FM for at least 1 year, had pain more than 50% of the time, and were willing to forgo the introduction of any new medications or other treatment for the duration of the study.

Depressive Symptoms

Patients' clinical pain was assessed immediately before the PET scan using the Short Form of the McGill Pain Questionnaire (SFMPQ). Patients' depressive symptoms were also assessed using the Center of Epidemiological Studies-Depression Scale.

PET imaging revealed FM patients had significant reductions in MOR BP compared with controls in the bilateral nucleus accumbens, the left amygdala, and the right dorsal anterior.

In addition, researchers found that, among FM patients, MOR BP was negatively correlated with clinical pain ratings in the affective, but not the sensory, dimension of pain. "We looked specifically at the ratio between the affective and the sensory dimensions of pain and found that those people who have more of the affective dimension of pain, which is a measure of the unpleasantness of the pain sensation, have lower binding potential, mostly in the cingulate regions," he said.

Finally, the study showed that patients with more depressive symptoms had greater reductions of MOR BP, particularly in the amygdala.

Need for Alternate Therapies

Dr. Harris said he was surprised to find reductions in receptor availability were local, rather than global.

"Based on a previous study, where we found elevated opioid levels in the CSF, I anticipated we would see reductions in receptor availability throughout the brain. However, what we observed was reduced receptor binding limited to very discrete and focal brain regions," he said.

To date, said Dr. Harris, there have been no randomized, controlled trials of exogenous opioids in FM. However, he added, the findings of the current study suggest the results of such a trial could be negative.

Future research by his team will focus on gaining a better understanding of the pain mechanisms in FM as well as the development of alternative, potentially more effective, therapies for these patients.

This 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 (NIH); and the NIH. Dr. Harris was supported by an NIH?National Center for Complementary and Alternative Medicine grant.

J Neurosci. 2007;27:10000 -10006. Abstract

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I've had fibro for 32 years now and have never used anything for the pain, which at times, has been pretty darn awful. I guess I'm glad now, because it probably wouldn't have helped and I would have become dependent on something that wasn't very useful to begin with.

One of the reasons I have never taken pain meds is because of the stigma associated with fibro, and the "addictive" behavior of us. It is refreshing to see more and more research disproving the stereotyping. Thanks doctorguest! I know we still have a ways to go, but every milestone, no matter how small, is a good thing. morgan

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I've had fibromyalgia since I was 17, which would be 16 years now. Darvocet was the only thing that helped me for YEARS. I only used it for pain that ranked from 7 - 8 on a scale of 10 (...never rated myself higher than that, as I believe my pain has never been as bad as it could possibly be). I always found it dulled the pain to the point that it was manageable. Although, it could very well be that I just didn't CARE about the pain anymore.

I still use it today for severe breakthrough pain, but, thank God, my UConn doctor, and Eli Lilly & Co., Cymbalta has been a miracle for my pain. My script of Darvocet is for 20 pills, and that lasts me four months or more, now.

This study is actually a little disconcerting. Results like these could be used to justify withholding pain medication from those in pain.

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I hope the results are not used to withhold opiates from patients. I also take these studies with a grain of salt - yes, 'possibly' the opiates may not be effective in some patients with fibromyalgia - they did study only 17 patients! But this is not a reason not to prescribe it, in my opinion; it may actually help, and if used appropriately, would not be addictive.

Lately, I've been seeing more and more studies being published on fibromyalgia, a disorder which is probably rooted in the autonomic dysfunction as well - though we don't have the actual proof of this yet. Some of their findings may also apply to POTS patients although one needs to be careful not to overinterpret these (note to self ;).

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I read this article awhile ago. I found it very interesting. After 30 years of working in the health care field, I know there is a fair amount of friction between many "traditional" and "holistic" practitioners.

I thought the same thing you did DG, as did my doctor. He is very much a believer in Fibro, so I am fortunate in that regard, but I don't even tell other doctors I have it. I wondered why he was so vague, but my thoughts were, he must have a book or online stuff. Not that I don't think he's pretty spot on, just that he was so vague about remedies.

Holistic and traditional medicine is like these bizarre illnesses. They have a long way to go before they come together. So, as much sense as he makes on much of this, I would have to wonder how many doctors would be open to his treatments, if he had listed them. I have a very open and liberal doctor, but even he is a bit hesitant about holistic approaches. Like everything else, we have a ways to go on this front. morgan

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Alternative and Holistic health treatments have their place but I think it's how one INTERPRETS what is holistic and is valid.

For instance, Reiki treatments seem real to many who get them in treatment.

Others do Reikie "long distance by phone" ? My ANS endocrinologist doc is into western and easter medicine philosophies and even that LONG DISTANCE REIKI does not fly with him.

That would be like acupuncture by phone and we know acupuncture can be VERY beneficial for pain and other ailments.

Herbs and supplements from health food stores are a double edges swords. If you take the SALESPERSON word for granted, you can be in trouble and take too much of a substance NOT REGULATED by dose per capsule or pill.

So, unless you have been reading about nutrition, health and herbs for 20 years, as I have, you may be SWAYED by the HYPE and Baloney much like the drug companies ADVERTISES to the public on the tv.

Also, if a doc wants HUNDREDS or THOUSANDS of dollars for a "HOLISTIC TREATMENT" or "nutritional guidance", RED FLAG! RED FLAG.

I have tried many things for Fm and sometimes it's ok, other times it's just hovering in the background and other times I am flat on my back on the floor on a comforter with an ice pack under my neck. PAINFUL. Pain meds sometimes have worked and sometimes make me sick.

But with the worsening POTS, I have to get the pain under control or I get so tachy and blackouts when I stand...

No easy ONE SIZE FITS ALL for anybody but I HATE articles or docs that "with hold pain meds" to those desperately in neeed.

I had another point but it just went out my head. :)

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