Study Confirms Fibromyalgia Pain

Discussion in 'Fibromyalgia Main Forum' started by matthewson, Aug 4, 2005.

  1. matthewson

    matthewson New Member

    Something you might want to print out and show to people who don't believe in the pain of FMS.

    ANN ARBOR, MI - A new brain-scan study confirms scientifically what fibromyalgia patients have been telling a skeptical medical community for years: They're really in pain.

    In fact, the study finds, people with fibromyalgia say they feel severe pain, and have measurable pain signals in their brains, from a gentle finger squeeze that barely feels unpleasant to people without the disease. The squeeze's force must be doubled to cause healthy people to feel the same level of pain - and their pain signals show up in different brain areas.

    The results, published in the May issue of Arthritis & Rheumatism, the journal of the American College of Rheumatology, may offer the proof of fibromyalgia's physical roots that many doubtful physicians have sought. It may also open doors for further research on the still-unknown causes of the disease, which affects more than 2 percent of Americans, mainly women.

    Lead authors Richard Gracely, Ph.D., and Daniel Clauw, M.D., did the study at Georgetown University Medical Center and the National Institutes of Health, but are now continuing the work at the University of Michigan Health System. In an editorial in the same issue, Clauw and U-M rheumatologist Leslie Crofford, M.D., stress the importance of fibromyalgia research and care.

    To correlate subjective pain sensation with objective views of brain signals, the researchers used a super-fast form of MRI brain imaging, called functional MRI or fMRI, on 16 fibromyalgia patients and 16 people without the disease. As a result, they say, the study offers the first objective method for corroborating what fibromyalgia patients report they feel, and what's going on in their brains at the precise moment they feel it. And, it gives researchers a road map of the areas of the brain that are most - and least - active when patients feel pain.

    "The fMRI technology gave us a unique opportunity to look at the neurobiology underlying tenderness, which is a hallmark of fibromyalgia," says Clauw. "These results, combined with other work done by our group and others, have convinced us that some pathologic process is making these patients more sensitive. For some reason, still unknown, there's a neurobiological amplification of their pain signals."

    Further results from the study were presented last year at the ACR annual meeting. The project will continue later this year at UMHS, joining other fMRI fibromyalgia research now under way.

    For decades, patients and physicians have built a case that fibromyalgia is a specific, diagnosable chronic disease, characterized by tenderness and stiffness all over the body as well as fatigue, headaches, gastrointestinal problems and depression. Many patients with the disease find it interferes with their work, family and personal life. Statistics show that far more women than men are affected, and that it occurs mostly during the childbearing years.

    The ACR released classification criteria for fibromyalgia in 1990, to help doctors diagnose it and rule out other chronic pain conditions. Clauw and Crofford's editorial looks at the current state of research, and calls for rheumatologists to take the lead in fibromyalgia care and science.

    But many skeptics have debated the very existence of fibromyalgia as a clearly distinct disorder, saying it seemed to be rooted more in psychological and social factors than in physical, biological causes. Their argument has been bolstered by the failure of research to find a clear cause, an effective treatment, or a non-subjective way of assessing patients.

    While the debate has raged, neuroscientists have begun to use brain scan technology to identify the areas of the normal human brain that become most active during pain. A few studies have even assessed the blood flow in those areas in fibromyalgia patients during baseline brain scans. The new study is the first to use both high-speed scanning and a painful stimulus.

    In the study, fibromyalgia patients and healthy control subjects had their brains scanned for more than 10 minutes while a small, piston-controlled device applied precisely calibrated, rapidly pulsing pressure to the base of their left thumbnail. The pressures were varied over time, using painful and non-painful levels that had been set for each patient prior to the scan.

    The study's design gave two opportunities to compare patients and controls: the pressure levels at which the pain rating given by patients and control subjects was the same, and the rating that the two different types of participants gave when the same level of pressure was applied.

    The researchers found that it only took a mild pressure to produce self-reported feelings of pain in the fibromyalgia patients, while the control subjects tolerated the same pressure with little pain.

    "In the patients, that same mild pressure also produced measurable brain responses in areas that process the sensation of pain," says Clauw. "But the same kind of brain responses weren't seen in control subjects until the pressure on their thumb was more than doubled."

    Though brain activity increased in many of the same areas in both patients and control subjects, there were striking differences too. Patients feeling pain from mild pressure had increased activity in 12 areas of their brains, while the control subjects feeling the same pressure had activation in only two areas. When the pressure on the control subjects' thumbs was increased, so did their pain rating and the number of brain areas activated. But only eight of the areas were the same as those in patients' brains.

    In all, the fibromyalgia patients' brains had both some areas that were activated in them but not in controls, and some areas that stayed "quiet" in them but became active in the brains of controls feeling the same level of pain. This response suggests that patients have enhanced response to pain in some brain regions, and a diminished response in others, Clauw says.

    The study was supported in part by the National Fibromyalgia Research Association, the U.S. Army and the NIH. In addition to Clauw and Gracely, the research team included Frank Petzke, M.D.; and Julie M. Wolf, BA.

    Took your advice Jeanne and changed the title of the post.

    Take care, Sally

    [This Message was Edited on 08/06/2005]
  2. Jeanne-in-Canada

    Jeanne-in-Canada New Member

    and this article is worth doing cartwheels over, if my darn back wasn't so sore (and if 12 areas of my brain weren't lit up like a Christmas tree).

  3. Jeanne-in-Canada

    Jeanne-in-Canada New Member

    This is from the Townsend Letters:

    The Role of the Brain and Mast Cells in MCS

    by Gunnar Heuser, MD, PhD, FACP

    Multiple Chemical Sensitivity (MCS) was first described in the 1980s, yet it has remained controversial. The resistance to the concept of MCS has come from scientists who pointed out the lack of solid scientific diagnostic tests. It has also come from the industry which has trouble accepting the proposition that their products make a great number of people sick.

    My personal experience (I have evaluated several thousands of chemically injured patients) has convinced me that MCS is based on a physiological and not on a psychological mechanism. This is why I have been interested in finding objective evidence for MCS. In this paper I will present a mast cell hypothesis, a limbic system hypothesis, and an office approach to objective testing for MCS.

    Mast Cell Disorder and MCS

    Patients with mastocytosis can be exquisitely sensitive to even small amounts of chemicals. When mast cells discharge histamines and other compounds, patients often develop flushing and a metallic taste in their mouth.

    A few years ago I decided to test some of my patients for mast cell disease. Some of these patients with MCS actually turned out to have mastocytosis. Other patients were found to have a mast cell disorder.

    All diagnoses were made on the basis of skin biopsies done in an area which on inspection and palpation, showed no evidence of abnormality. It was also made on the basis of an elevated tryptase (an enzyme produced by mast cells) level. If mast cells were present in excess and/or if tryptase levels were elevated we would make a diagnosis of mast cell disease or disorder, if the clinical picture was also consistent with that diagnosis. In a few patients we also used a bone marrow biopsy to assist in the diagnosis.

    Mastocytosis is considered to be a very rare disease. Yet, I have accumulated more then 20 patients with that diagnosis in a matter of two to three years.

    At this time our testing is done on a random basis. We are now developing a protocol by which we will introduce a challenge (e.g. perfume, nail polish, chemicals found in a carpet store, etc.) and then test at a time when the patient is symptomatic from that challenge.

    We also hope to work with the Mastocytosis Society1 in further developing diagnostic approaches to the overlapping syndromes of mastocytosis and MCS.

    At this time the diagnosis of MCS is considered justified only in the absence of diseases such as mastocytosis and porphyria.2 This exclusion will require that all patients with MCS be tested for mast cell disorder and porphyrinopathy. I believe that this indeed should be done.

    In summary I postulate that chemical injury can trigger a mast cell disorder which in turn can cause MCS. This concept was recently published.3

    Limbic Hypermetabolism and MCS

    Patients with MCS often show emotional instability during their reactions to small amounts of chemicals. This has been likened to the epileptogenic effects of kindling which is particularly effective in the limbic system of the brain. Yet no proof of this concept has come forward to date.

    We started doing PET brain scans on some of our patients with MCS and found that the limbic, hypothalamic and brain stem areas are hypermetabolic (in terms of their radioactive glucose uptakes) and therefore hyperactive (almost as seen during focal seizure activity).

    Since the limbic system contributes emotional reactions and interpretations to sensory input, and since patients with amygdaloid (the amygdala is part of the limbic system) seizures can develop panic and related attacks during an amygdaloid seizure, our data appear to explain the emotional instability during a reaction to chemicals.

    The previously mentioned structures also serve memory and cognitive as well as neuroendocrine and autonomic nervous system functions, all of which can be deranged in a patient with MCS.

    In summary, I have shown that patients with MCS can develop hyperactivity in deep structures of the brain and that this may explain their emotional instability which therefore develops on a physiological rather than psychological basis.

    It should be mentioned at this time that patients who are impaired and/or disabled from chemical injury and resultant MCS often become depressed. This depression would obviously be a natural reaction to their impairment and/or disability and therefore be a secondary depression.

    Our findings were first published in 19994 and will soon be published5 in proceedings of a meeting on Chemical Intolerance. In this volume, kindling and related mechanisms are also discussed.

    Challenge Testing in the Medical Office

    A few years ago, at a meeting on MCS, testing of patients in an environmental chamber was suggested as the most scientific approach to proving MCS. This suggestion proved impractical which is why so few publications exist which provide a protocol for testing a patient for MCS.

    In my office we have developed a protocol by which a patient first undergoes baseline testing of pulmonary and immune functions as well as 24-hour urine collection for porphyrin fractions. Then the patient voluntarily inhales (via mouth and nose) nail polish, perfume, or exposes himself/herself to a chemical environment. Once symptomatic from that exposure, the patient undergoes follow-up testing of the same parameters and of course, undergoes a follow-up physical examination with special attention to neurological abnormalities and/or changes on auscultation of the lungs.

    Ideally, the patient brings a non-sensitive person (age and sex matched) who undergoes the same testing. Patient and volunteer (control) are carefully observed by my office staff who make detailed notes.

    Table 1 shows comparison of some immune parameters with regard to the above-mentioned tests. So far, we have found that MCS patients indeed respond more to chemical exposure than their controls. This is also true of pulmonary function which is more impaired when the patient becomes symptomatic after exposure to a small amount of chemicals (see table 2).

    We addressed elevation of TA1 (CD3+CD26+) cells in an earlier publication.6 Our data on T3+ (CD3) cells are unpublished. These cells can, in my opinion, be used as indicators of reactions to chemicals although they do not seem to contribute to any symptomatology.

    We are in the process of adding additional measurements (e.g. cerebral blood flow, tryptase blood levels, and others) to our protocol. Naturally, we do challenge testing only when the patient needs to prove MCS to Social Security, insurance carriers (long-term disability) and the courts. We are slowly accumulating data for future publication in a peer-reviewed journal.

    If other interested physicians were to use our approach, data would quickly accumulate and hopefully become statistically significant much sooner than using an environmental chamber approach in an academic setting.

    In summary, I have shown approaches to MCS which in my opinion are promising and will help to further define the mechanisms underlying the development of MCS.


    Gunnar Heuser, MD, PhD, FACP, FACFE, BCFE

    NeuroMed and NeuroTox Associates

    A Medical Group

    28240 W. Agoura Rd., Suite 203

    Agoura Hills, California 91301 USA


    Fax 818-865-8814


    1. The Mastocytosis Society, Inc. 2010 North Grand Avenue, Connersville, IN 47331.

    2. Bartha L, et al, Multiple chemical sensitivity: A 1999 consensus. Arch Environ Hlth 1999; 54:147-149.

    3. Heuser G, Letter to the editor regarding Mast cell disorder to be ruled out in MCS. Arch Environ Hlth 2000; 55:284-285.

    4. Heuser G, Wu JC, Subcortical hypermetabolism and cortical hypometabolism after neurotoxic exposure. Human PET studies. 7th International symposium on neurobehavioral methods and effects in occupational and environmental health. Stockholm, Sweden June 20-23, 1999.

    5. Heuser G, Wu JC, Deep subcortical (incl. limbic) hypermetabolism in patients with chemical intolerance. Human PET studies. Annals of the NY Academy of Sciences. 2001(in press).

    6. Heuser G, Wojdani A, Heuser S, Diagnostic markers of multiple chemical sensitivity. In: Multiple Chemical Sensitivities, Addendum to Biologic Markers in Immunotoxicology. National Academy Press, Washington, D.C. 1992; 117-138.

    Baseline + 4 hours + 20 hours

    TA1 # 820 1170 820 pt 1

    570 760 680 pt 2

    580 588 660 control

    T3 + # 1460 1880 1280 pt 1

    1460 1650 1440 pt 2

    1030 1170 1090 control

    Table 1 shows changes from baseline in two chemically sensitive patients exposed to perfume. Note lesser or no change in age and sex matched control when counting TA1 and T3 + cells four and twenty hours after exposure.

    pt. 1 pt. 2 control

    FEV 0.5 -25 +11 +37

    FEV 1 -11 -5 +5

    FEV 1/FVC -3 -4 +3

    FEF 25-75% -33 -14 -5

    Table 2. % changes in some parameters of pulmonary function in two chemically sensitive patients in comparison with an age and sex matched control after exposure to perfume.

  4. matthewson

    matthewson New Member

    I like Dr. Clauw's work also! He has a few studies going on right now and is looking for control patients and FMS patients. I just printed out the forms last night to participate in a trial.

    It is one to see if acupuncture can help with the pain of FMS. You either get fake acupuncture or real, you won't know. I figure I would be an impartial candidate because I have never had acupuncture, so I wouldn't know if they were giving me fake acupuncture or not!

    The other one I am interested in is Auditory perceptions of Fibromyalgia patients. I can not STAND loud music anymore! I don't know if that is particularly related to FMS or just getting older.

    The testing is done about 10 minutes from my house, so I don't have to drive far. And they pay you, although I would do it for free to help with the research.

    I had been thinking about going back for a master's in clinical research techniques in order to actually work on clinical testing, but my cognitive functions seem to be getting worse, and I don't know if I could make it through the program!

    Take care, Sally
  5. Jeanne-in-Canada

    Jeanne-in-Canada New Member

    It has to do w/ impaired adrenals and causes sensory distortion. I get it all, sound, vision, smell, touch (of course),I think I'm forgetting one, but I know I get them all. From what I see here, most get them too.

    These are important studies and everyone should see them. You might garner more interest if you change the title. Just a thought.

  6. matthewson

    matthewson New Member

  7. Mikie

    Mikie Moderator

    For these articles.

    Love, Mikie
  8. tansy

    tansy New Member

    I have not been Dx with FM, never had it checked for, but I was given the dustbin Dx of chronic pain syndrome when they failed to check for the sources of my most severe pain. I have ME/CFS, lyme, and problems with my spine; the pain (including neuropathic) gives me some insight into what living with severe FM day in day out must be like.

    Sally I have traditional acupuncture but not specifically for pain. There was a study in the UK published recently, physiological changes were confirmed by PET scans. If a trial of acupuncture proves effective for pain relief in FM, or an indentifiable subset with FM, then hopefully it would lead this treatment being funded for everyone who would benefit.



    Acupuncture 'more than a placebo'

    Scientists say they have proof that acupuncture works in its own right.

    Sceptics have said that any benefits gained from acupuncture are merely down to a person's expectation that the treatment will work.
    But researchers at University College London and Southampton University say they have separated out this placebo effect.
    Their findings, based on a series of experiments and brain scan results, are published in the journal NeuroImage.

    Dummy treatment

    The researchers used positron emission tomography (PET) scans to see what was happening in the brains of people having acupuncture treatment for arthritis pain.

    Each of the 14 volunteers underwent each of three interventions in a random order.
    In one intervention, patients were touched with blunt needles but were aware that the needle would not pierce the skin and that it did not have any therapeutic value.
    Another intervention involved treatment with specially developed "trick" needles that give the impression that the skin was being penetrated even though the needles never actually pierced the skin.

    The needles worked like stage daggers, with the tip disappearing into the body of the needle when pressure is applied. This was designed to make the patients believed that the treatment was real.

    The third intervention was real acupuncture.

    Brain activity

    When the researchers analysed the patients' PET scan results they found marked differences between the three interventions.

    Only the brain areas associated with the sensation of touch were activated when the volunteers were touched with the blunt needles.

    During the trick needle treatment, an area of the brain associated with the production of natural opiates - substances that act in a non-specific way to relieve pain - were activated.

    This same area was activated with the real acupuncture but, in addition, another region of the brain, the insular, was excited by the treatment.
    This was a pathway known to be associated with acupuncture treatment and thought to be involved in pain modulation.

    Sarah Williams of the British Acupuncture Council said: "This is very positive news for acupuncture and this latest research is an exciting illustration of what acupuncturists have known for a long time - that acupuncture works and its effectiveness goes beyond the placebo effect."

    Professor Henry McQuay, professor of pain relief at the University of Oxford and member of the Bandolier group that looks at the evidence behind different medical treatments, said: "The great bulk of the randomised controlled trials to date do not provide convincing evidence of pain relief over placebo.
    "Some people do report that acupuncture makes them feel better.
    "But it is extremely difficult, technically, to study acupuncture and tease out the placebo effect."

    Story from BBC NEWS:
    Published: 2005/04/30 22:57:58 GMT

    [This Message was Edited on 08/06/2005]
  9. fivesue

    fivesue New Member

    online, about FM and Depression together. The results of the study showed that FM affects one part of the brain in relation to feeling pain while depression affects another; therefore, it concludes that just treating for depression will not automatically cure the pain in FM.'s in the head, but not the part of the head people accuse of us of being sick in, if you get my drift. (-:

    Great articles. I'm thinking of sending the article to the rheumy I just saw...and my PCP...and maybe print it in the local paper...well, maybe not the last, but certainly the first two mentioned.

    Thank you again for the materials.