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mrsD 05-20-2007 08:47 AM

New medical thoughts on Fibro:
I don't normally post here...but I want to share some information that came my way on Friday. I attended a long complex medical conference on Chronic Pain, and one portion dealt with Fibromyalgia.

The professor Daniel J. Clauw MD was just excellent.

He is currently teaching the new data about Fibro to residents and staff at the University of Michigan. There is new data about what Fibro really is, and what methods treat it most effectively.

Some searches on Google using his name will bring up papers like this:

I will try to summarize what I found important, and if you search further, you will find more on this subject.

1) "Tender" point analysis is being dropped in diagnosing Fibro. And new research into genetics and neurotransmitter actions in the brain are showing that there is an 8 fold increase in fibro among first degree relatives. And that pain perception of ANY stimulus (not just trigger points) is exaggerated in fibro sufferers.

2) The genes being looked at are 5HT2a receptor polymorphism T/T phenotype, serotonin transporter, dopamine D4 receptor exon II repeat polymorphism, and COMT (catecholamine o-methyl transferase)..which is involved in pain transmission.
In other words, the pain circuits in the brain are faulty and over-reactive.

3) Not everyone with the genes develop FM... there are triggers. A portion of the brain, that evaluates subjective sensory data, can be overactive and there can be autonomic and neuroendocrine dysfunctions.
Some of the triggers are:
a) peripheral pain syndromes
b) Infections esp with parvovirus, Epstein-Barr Virus, Lyme disease, Q fever (in Australia/New Zealand), uncommon upper respiratory infections.
c) physical trauma (automobile accidents)
d) hormone errors, such as hypothyroidism
e) some drugs (sorry he didn't list those)
f) vaccines
g) certain catastrophic events like WAR, but natural disasters and 9/11 attack did not show increase during studies. So the catastrophic event data is pretty strange IMO.

I won't go into the amazing details of neuronal functioning, but Dr. Clauw did give this list:
Facilitators in sensory processing + factors are:
Substance P
Glutamate and EAA (I don't recall what EAA is)
Serotonin 5HT2a 3a receptors
Neurotensin (a cytokine)
Nerve Growth factor
CCK (cholecystakinin)

Inhibiting factors - are:
Decending anti sensory pathways which include
Norepinephrine/Serotonin 5HT1a, b


Now this sounds very complex, but using drugs successfully in Fibro patients depends on understanding where these drugs can work.

I am going to skip now to treatments, and comment that some of you will NOT like the following. I myself, do not see reflections of these treatments in the public yet.

Strong evidence in studies for the following drugs:
a) tricyclic antidepressants-- Elavil(amitriptyline) and Flexeril--Dr. Clauw's most successful use is with Flexeril given at bedtime. He starts at 5mg/night and ramps up to perhaps 20mg if needed.

b) anticonvulsants-- gabapentin (Neurontin) and pregabalin (Lyrica). The Lyrica may need to be upwards to 600mg/day

c) Dual antidepressants with both norepi/serotonin actions:
venaflaxine (Effexor), Milnacipran (a new drug very promising with few side effects being evaluated now by FDA soon to be passed--very successful in other countries), and duloxetine (Cymbalta).

Modest Evidence:
a) tramadol (Ultram) for pain (this may interact with Flexeril care needs to be taken if both drugs are used)
b) SSRI andtidepressants like Prozac (he says this one is best), Paxil, Celexa, Zoloft

Weak Evidence:
Human Growth hormone, 5HTP (an OTC supplement), tropisetron ( I don't think this is available yet in USA), and
SAMe (s-adenosyl methionine) an OTC supplement

NO EVIDENCE of effectiveness:
Opioids (narcotics), corticosteroids (prednisone), NSAIDs like ibuprofen etc,
Benzodiazepines (Klonopin), and nonbenzo sleeping meds (Ambien/Lunesta),
and guanifenesin (Robitussin).

Now the reason given about the Opiods...and I expect this factor to be hotly responded to that studies were done on the internal receptors in the brain of Fibro patients for endorphin/enkephalin sites. It was found that these are overactive and all filled by endogenous molecules, and that there is no room for opiates to engage the receptors. Dr. Clauw said that Fibro is an upregulated condition where the body is already producing alot of internal opiates for this system.

Non-Drug therapies:

Strong evidence for improvement:
Education/understanding the condition and how it manifests
Aerobic exercise (start a few months after drugs are working)
Cognitive behavioral therapy

Modest Evidence for:
Strength training
hypnotherapy, biofeedback, and water therapy/exercise

Weak evidence:
acupuncture, chiropractic, massage therapy, electrotherapy, ultrasound

No evidence for:
tender trigger point injections, flexibility exercises.

Dr. Clauw over the years has changed his practice from where he would teach each new patient about 20 mins about fibro. He found that it was not long enough. So now he gives FREE afternoons to patients referred to him locally on the subject. If you are in SE Michigan, you can call for an appointment for one of these free lectures. He is a great speaker and very very knowledgeable and concerned.

Fibro is a very complex problem, and is now overlapping with other syndromes thought to be upregulated over stimulated conditions. IBS TMJ, low back pain, tension headache are examples.

If there is a damaged peripheral area of the body, then NSAIDs and opiods may be used cautiously. Examples are Osteoarthritis, Rheumatoid arthritis, and cancer. But if the pain is CENTRAL he feels use of opiods are not indicated and not useful. And as a matter of fact, in chronic Headache, use of opiods is now being discouraged, since new data shows that they perpetuate the cycle of central pain, and it is now not uncommon to show opiods actually causing chronic headache! But that is another topic, covered in this long seminar!;)

Dr. Clauw was unusual in other respects...he had no ties to drug companies in the disclosure statements. And he did not want to discuss off label use of other drugs at length. This is for liability reasons, and also because data is lacking at this time for those other agents.

Also, I am only the messenger here, so please keep that in mind! ;)

Judy2 05-20-2007 11:17 AM

Thank you so much mrsd for sharing this information with us! First of all, it's encouraging to hear that there are medical professionals out there who actually believe in this condition and realize it's not "all in our heads"!

Alot of what you said hits the mark in my particular situation. Narcotics - tried many of them and only succeeded in feeling like a zombie. The NASAIDS did nothing as far as pain. Trigger point injections -- OUCH!! Don't know what she hit, but almost threw up and passed out from the pain with no good result as well.

Goes along with an overactive immune system -- I also have MS which is thought to be the same. Triggered by a drug -- my fibro started while on one of the injectable drugs for MS. It is interesting to note that the pain doesn't come solely from the "trigger points". For example, I've found trying to crawl on my hands and knees is impossible because of the pain. Even on carpet, it feels like my knees are on broken glass.

At my up-coming neuro appointment, I'm planning on requesting a muscle relaxant for spasticity so guess I'll try Flexeril!

Did he mention any connection with weather changes since most of us experience excessive pain then, especially when the barometer is falling?

Osteoarthritis, yes, since my 20's. Family connection? Seems like everything was called arthritis or rheumatism. So far the only thing I've found that takes the edge off is Aleve (naproxin).

Thank you again and please keep us informed if anything else new develops!

fiberowendy2000 05-21-2007 08:15 AM

Dr. Clauw is a very good researcher/doctor who does what my doc does on the east coast. They are buddies and know each other very well. Slowly they are breaking the code of FM but it is taking time and most docs are just doing what they need to do to keep their FM patients as pain free as possble.
Hopefully some use of meds available now will help. I have been down the road of all those meds and none of them worked. Only muscle relaxants and trigger point injections help so far. I am also on anti-d's and they only help so much too.
Please relief soon!

Sydney 05-28-2007 09:53 AM

Thank you Mrs. D for the information
As always you are always there to help all of us with our complex medical condition. Thank you for recognizing the need to help those of us who deal with "beast" of fibro. The info you provided was most interesting and I am relieved that someone is finally looking into the genetics of the disease. As you may remember I have both fibro and RSD as well as now TMJ and burning mouth from chloral hydrate.
I do agree with him about the use of morphine - no help. Dr. Hooshmand really was against using that drug and said it would set you up for increased levels of pain. However, the exercise part he recommends is really impossible for me as I can do only minimal walking due to both RSD and fibro in back and now burning in soles of feet.
I plan on taking this article to all of my drs. to show them so they can understand my full body sensitivity issue. Some of them just "don't get it" when I say "don't touch me". This article clarifies this.
You are truly so kind to be of so much help to so many.
I am going to also post on the medications forum to ask a question.

buckwheat 05-29-2007 11:19 AM

Hi Their,

Thanks so much for taking the time to post. Do you think PCR testing could help? I would appreciate your thoughts and wisdom on this. Much Love, Roz

coyote 06-02-2007 05:05 PM

Thanks for the new source of info for me. I'll pass it on.

FIBEROWENDY, who is the doc you see on the East Coast. Mine does as little as possible.


Originally Posted by fiberowendy2000 (Post 102761)
Dr. Clauw is a very good researcher/doctor who does what my doc does on the east coast. They are buddies and know each other very well. Slowly they are breaking the code of FM but it is taking time and most docs are just doing what they need to do to keep their FM patients as pain free as possble.
Hopefully some use of meds available now will help. I have been down the road of all those meds and none of them worked. Only muscle relaxants and trigger point injections help so far. I am also on anti-d's and they only help so much too.
Please relief soon!

fiberowendy2000 06-03-2007 05:29 AM

Coyote. The doctor I see is Dr. Don L. Goldenberg out of Newton Wellesley Hospital. I see him about once a year or so. He gives me the latest info and he keeps up with my progress on how I am feeling. He's a great guy. He doesn't prescribe anything just recommends to your primary what should be done for you. I tell you I don't know how many times that letter from my initial visit has saved me with new docs.
He knows Dr. Clauw and others doing research since he does the same things. Last time I saw him, he recommended taking vitamin D supplements along with your regular vitamins.
So there is a new fibro doc for those in the Boston area.

AUGOLDMINER 06-04-2007 01:14 AM

My view is he is missing a subset of fibro. That is the people that have fibro due to autoimmune disorders.
I have been through the anti depressants and none of them work. And the dose was to the level that i started to get serotonin syndrome.

I do not have depression. My fibro is due to damage by autoantibodies and high levels of INTERLEUKIN 6 from castleman's disease.

I do not believe that fibro is one disorder i believe that it is a group of disorders.
in many ways it is like MS or diabetes
In MS you have 4 different types. An diabetes you have type 1 and type 2

I believe that my fibro is due to low levels of GABA and/or Glycine in the CNS
The best meds i have found for my fibro are Gabapentin and a over the counter GABA supplement.
TO THIS DAY I HAVE DOCTORS THAT STILL WANT TO PUT ME BACK ON ANTI DEPRESSANTS. even through they do not work and the side affects are worse then the fibro. why because most doctors are trained that anti depressant are the best meds for fibro. even if they dont work.

mrsD 06-04-2007 05:01 AM

I am glad this thread is being read and
generating questions.

It was difficult for me to condense the information presented by Dr. Clauw which
was a power point type thing... my syllabus does not have text, only power point slide copies.

First off... the main thrust of his lecture was the definition of fibro.
This syndrome is basically an overresponse by the nervous system to sensory and pain stimuli. In a fibro person (who inherits this tendency) is like a radio turned up to full volume all the time. In normal people there are feedback loops in the brain to turn DOWN stimuli, after they are perceived. In fibro this does not happen. So ALL stimuli tend to be preceived as noxious.

The facilitator compounds listed:

Facilitators in sensory processing + factors are:
Substance P
Glutamate and EAA (I don't recall what EAA is)
Serotonin 5HT2a 3a receptors
Neurotensin (a cytokine)
Nerve Growth factor
CCK (cholecystakinin)
are in excess in fibro. So Pharma is looking at antagonists to these receptors.
For example a substance P antagonist is in phase II or III trials right now. Its target is depression, but it may prove helpful to fibro patients. I posted this on our Depression forum.

The inhibitor compounds:

Inhibiting factors - are:
Decending anti sensory pathways which include
Norepinephrine/Serotonin 5HT1a, b
Opioids (endorphins)
are being looked at as reducers of fibro symptoms by increasing their activity at receptor level.

The pain loop is a complex circuit of ascending and descending fibers, and is really too complex to go into here.

Now if you look at the Most valuable treatments... gabapentin and Lyrica are listed as primary interventions at this time. Both do NOT affect GABA per is there pharmacology:

Mechanism of Action

LYRICA (pregabalin) binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin’s antinociceptive and antiseizure effects in animal models. in vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.

While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
The GABA functions are not primary but peripheral, and still not understood.

I would like to comment to Augoldminer...that some patients over the years on this board and Braintalk, have seen improvement in MS type symptoms and fibro by going on the gluten free diet. Gluten is a primary trigger for autoimmune issues in some patients. Some even do casein and corn elimination diets and find response to those as well.

Autoimmune issues can be triggered by viruses, and vaccines as well.
And they may exist in patients IN ADDITION to fibro..often people have several issues, which may or may not overlap.

Dr. Clauw believes that fibro is a genetically transmitted syndrome, and does not occur in certain people, because they lack the genetic error that allows the pain receptors to go into overdrive. That is his opinion at this time.

L-glutamine is thought to inhance GABA functions, and I have seen Inositol also recommended for this (it improves glucose utilization in the brain).

While Dr. Clauw does not work for drug companies, he did suggest that the combination SSNi and SSRi drugs help more than plain SSRi types. The new drug Milnacipran is very effective with very few side effects now used in other countries. It is very close to FDA approval here and may be available in one year or so.

I will also add that Dr. Clauw said that Fibro is the "last great frontier" that the drug companies are looking towards...
they want to find effective pharma agents because...well, frankly there is a huge financial gain to it. He predicts "blockbuster"
agents in the near future.

Here is the link to the new agent that may help with blocking excess substance P:

Midge 06-10-2007 12:34 AM

I was a volunteer in the milnaciprin study and had a bad reaction to it. I broke out in huge welts on my thighs a few hours after half an initial dose. It's obvious I was on the drug - not placebo. It was a long hassle to get into the study and once in they tried to keep me in even though I reacted badly. Have also been in lyrica study that made me feel terrible. Started throwing it out. I'm not sure how well the adverse reactions are really recorded. I've been diagnosed w/mild fibro but think it's getting worse and/or I have other disease. I thought the glucosamine chondroitin was some help but gave me terrible stomach ache and diarrhea - of course I'm allergic to iodine. The anti depressants really scare me - have refused that route. No narcs either. Hope to find something!

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