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Dopamine and Fibromyalgia

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PVLady

New Member
This is very interesting article about how our "autonomic nervous system" dysfunction can be the cause of fibromyalgia, anxiety attacks, sleep disorders, etc. We should take a copy of this article to your doctors who think fibro is all in your head.


By Andrew J. Holman, M.D.

Assistant Clinical Professor, University of Washington
Clinical Rheumatologist, Pacific Rheumatology Assoc.
Website: www.Pacific-Rheumatology.com


Dopamine & Fibromyalgia


After centuries of disrespect and scorn, no one questions the validity of Parkinson’s disease today. It is ironic that the same neurotransmitter, dopamine, appears to play a control role in another enigma: fibromyalgia.

The historic similarities are striking as evidence of dopaminergic control mechanisms begin to emerge with respect to pain, sleep, arousal and the autonomic nervous system. Each of these central nervous system functions are relevant to fibromyalgia, but hopefully FM will be sorted out and effectively treated more quickly compared to Parkinson’s disease patients.

Mainstream research in fibromyalgia has followed a logical and respectable pathway to establish the veracity of abnormal central brain pain processing abnormalities in fibromyalgia.2 Almost anything measurable has been measured in patients in fibromyalgia.

But, dopamine is not measurable, except in samples of cerebrospinal fluid requiring a lumbar puncture. In addition, the five newly discovered dopamine receptors and their independent functions are not yet measurable. Brain biopsies remain an unattractive option for patients and researchers.

Since it cannot be easily measured, dopamine has not attracted much attention. Dopamine is not measured in Parkinson’s disease patients, either. So, how did study of dopamine become the backbone of Parkinson’s disease research and emerge as an important issue for patients with FM?

Serendipity. A drug, Levo-dopa, the precursor for dopamine, miraculously reversed Parkinson’s disease symptoms for the first time over a half a century ago. The unexpected clinical response shook the world.

There are many examples of serendipity in medicine. It fueled another medical field when a fungal contaminant in a laboratory experiment left overnight appeared to unexpectedly kill a bacterial culture. Serendipity revealed that this particular mold naturally produced penicillin to protect itself from bacteria:

as a result, a new world of antibiotics was born. Sometimes years of selfless labor at the bench top leads to discovery and cure, and sometimes serendipity plays an equally important role.

Such an analysis of the clinical response to a specific treatment can prove very useful, especially when the medical intervention is specific. If we know enough about how a drug works, and see a dramatic clinical response to it, then we may be able to work back to understand the original disease.

So far, patients with fibromyalgia and researchers dedicated to finding an effective treatment have been deserted by serendipity. The hard work has been admirable, but there has not been much good luck or many breaks.

We have studies that demonstrate a ‘statistically significant’ benefit, but it is usually mathematical significance more than clinical significance. Our best placebo-controlled trials, such as those for tramadol,3 fluoxetine, and amitriptyline,4 only produced an average improvement of 35% in a few parameters like pain, fatigue, or function.

While some patients may respond dramatically to a variety of therapeutic options, many more are left behind.

There is no cure for fibromyalgia, but some serendipity may have surfaced somewhat analogous to that seen years ago for patients with Parkinson’s disease.

In October 2004, at the American College of Rheumatology Annual Meeting, the first randomized, placebo-controlled trial of pramipexole was reported as a late breaking abstract.5 Comparing trials by the benchmark of how many patients achieve a >50% reduction in pain, those taking pramipexole for 14 weeks achieved possibly the highest level of response to any single medication yet tested for fibromyalgia.

To be fair, not all patients responded. However, the clinical response to pramipexole and the implications for further study of dopamine were equally important.

Pramipexole is a medication with very limited human effects. Unlike many other centrally acting medications, pramipexole stimulates only one receptor family (D2) and primarily one receptor, the dopamine 3 receptor (D3).6


Consequently, we need to know much more about the role of dopamine and specifically, the role of D3 in the cause and perpetuation of fibromyalgia.

Pramipexole is FDA-approved for treatment of Parkinson’s disease and is typically dosed 0.25-1.5 mg up to three times per day. The recent fibromyalgia study dosed pramipexole in increasing doses each week up to a target dose of 4.5 mg at bedtime after 14 weeks.

Both the unique nighttime dosing and the gradual escalation to the target dose were important. While the nighttime dosing scheme was also explored in earlier reports dating back to 20027 and 2000,8,9 this study in 60 patients was the first placebo-controlled trial.

Patients with restless legs syndrome (RLS) also take pramipexole, as well as the only other available D3 receptor agonist, ropinirole, at bedtime.

Neither medication has been FDA-approved for this indication although ropinirole may be indicated for RLS within the year.

Similar to fibro-myalgia, the cause of RLS is not known, but all medications approved to treat Parkinson’s disease are generally helpful for patients with RLS. The utility of other Parkinson’s medications for fibromyalgia is unclear,10 but a large ropinirole trial for fibromyalgia is currently underway in Europe.

We need to discover the role of dopamine, and more specifically the D3 receptor, in fibromyalgia. While some may argue that no medication has only one biochemical effect, a preponderance of the basic science evidence would argue against another unforeseen effect.

Still, it would be foolish to ignore the past and make assumptions without further evidence.

Unlike the penicillin story, my patients with fibromyalgia were not left in a petri dish overnight and ‘contaminated’ with pramipexole.

The logic of considering pramipexole at heretofore inconceivably high doses at bedtime was grounded in a logical approach spanning about ten years.

While traditionalists with significant grant resources assayed and measured neurotransmitters, hormones, muscle function, and exercise parameters and tested muscle relaxants, sedative hypnotics, antidepressants, analgesics, and neutraceuticals, I was interested in an extension of what Harvey Moldofsky described in 1975.


The Autonomic Nervous System


Moldofsky essentially reproduced symptoms of fibromyalgia 15 years before the American College of Rheumatology established specific criteria.

11 Patients developed global pain and tenderness after a few nights of sleep interrupted by a loud, auditory arousal during their deepest sleep stages (III/IV).12 A similar disruption of REM sleep did not cause fibromyalgia.13 Consequently, clinicians attempted to restore deep sleep with amitriptyline, cyclobenzaprine, and other anti-depressants and muscle relaxants with modest success.

However, many patients did not respond to this approach, and so research turned elsewhere abandoning the pivotal role of sleep deprivation. Increasingly, it seems that our usual pharma-cologic attempts to restore deep sleep fail, since these medications do not address the underlying excessive autonomic arousal.

At about the same time, in the late 1990’s, Martínez-Lavín described a fundamental abnormality of the autonomic nervous system inherent in fibromyalgia.14 Yunus also reviewed this concept15 and confirmed a much higher incidence of RLS in patients with fibromyalgia (30%) compared to controls (2%).16 I believed that Moldofsky was right, but there were two unforeseen problems.

First, his study preceded the establishment of criteria so readers were unsure if he had actually reproduced fibromyalgia. Secondly, we did not yet understand the role of his auditory arousal fragmenting deep sleep or the autonomic nature of arousal inherent in us all.

To make matters worse, Russell was unable to reproduce Moldofsky’s result in 1998.17 These events, and our ineffective attempts to induce ‘normal’ sleep encouraged most of my peers to believe that pain led to poor sleep and that we should focus more research on central pain processing errors, spinal cord neurotransmission, NMDA receptor dynamics affecting pain, and anything but sleep physiology.

I believe that they are all correct: Bennett, Martínez-Lavín, Russell, Moldofsky, Crofford, Clauw, and Yunus. They can all be correct if dopamine plays a pivotal role. The results of the Russell study can be rationalized by the fact that he did not completely duplicate Moldofsky’s experimental protocol.

While Moldofsky employed a startling, computer generated arousal, Russell allowed subjects to choose music. Both studies achieved fragmentation of deep sleep stages, but the arousal was important.

Music would not generally be considered startling, barring my children’s music. Interestingly, Lentz did reproduce Moldofsky’s findings and cause fibromyalgia in middle-aged women deprived of stage III-IV sleep in 1999.18

The startling nature of the arousal matters if one envisions that Martínez-Lavín and Yunus are right. Patients with fibromyalgia describe so much more than just sleep disturbance, fatigue, muscle spasm, and pain. Many other organ systems under the control of the autonomic nervous system are misbehaving.

Temperature regulation, sweat glands, gastric acidity, bowel motility, heart rate, blood pressure, and stress responses are often problematic. The role of the autonomic nervous system in fibromyalgia was already reviewed by Martínez-Lavín in a past issue of Fibromyalgia Frontiers (2002, Volume 10, #1).

When Moldofsky administered his auditory arousal, he activated a startle reflex, which arises from the autonomic nervous system. Consequently, we can either make patients sleep (overwhelm the arousal with sedating medications) or let them sleep (reduce the arousal).

Discovering a medication capable of turning down the autonomic arousal that fragments sleep to ‘let patients sleep’ is an intuitive but uncommon approach to fibromyalgia.

We have failed in our past attempts to induce proper, restorative sleep, but this theoretical approach to address unwanted nighttime arousal may be reasonable. Restore normal sleep, and we will all see if Moldofsky was indeed correct.

This theory of arousal fragmenting sleep led to another therapeutic pathway for patients with FM. Initially, I started to add medications capable of treating RLS to the medications of those fibromyalgia patients who had both FM and RLS. Both benzodiazepines, lorazepam, and clonazepam effectively treat RLS.

When added to a second medication able to deepen sleep, like a muscle relaxant or sedating antidepressant, fibromyalgia tender point scores decrease significantly.19,20 As a caveat, I initially met Harvey Moldofsky at my first poster presentation of this very data in 1998.

He encouraged me to consider this approach in patients with fibromyalgia who did not exhibit RLS symptoms. He intimated that some have EEG arousal similar to RLS and periodic limb movement, yet they do not move at night. He was correct.

Apparently, one can have RLS EEG activity and have no clinical features of RLS to report when interviewed. While colleague neurologists have no clear understanding of the actual pathogenesis of RLS, an excessive autonomic arousal state seems possible.

Other arousals that may reflect abnormal autonomic activity at night may include bruxism (grinding teeth), racing thoughts, and disruptive dreams. The sleep disturbance responsible for pain, fatigue, cognitive problems, and muscular spasm may simply be another consequence of excessive autonomic activity, a consequence attributable to its abnormal activity at night blocking the restorative benefits of deep sleep stages.

Therefore, controlling autonomic arousal becomes critical, and if RLS is one of many potential expressions of excessive autonomic arousal, then new RLS options should be considered for treatment of fibromyalgia. The best clinical response demonstrated in a RLS trial was attributable to the dopamine agonists, pramipexole21 and ropinirole.22 The doses used to treat RLS are generally lower, about 15% of those studied in fibromyalgia.

The higher doses of pramipexole appear to address fibromyalgia more effectively. The European study may provide additional insight regarding a therapeutic role for ropinirole.

The autonomic nervous system deals with housekeeping functions in the body, including survival. Crofford23 is correct to point out the many influences of the endocrine system on fibromyalgia, but each system, endocrine and autonomic, cannot work in isolation.

Both systems, the autonomic and the endocrine, coordinate their effects to work in concert to address endogenous and exogenous stressors. Eventually, we will be able to measure the autonomic nervous system at a biochemical level to see which system plays the primary role and which system follows the lead of the other.

Thyroid and adrenal aberrations certainly affect sleep quality, but an autonomic survival arousal intuitively seems a more potent inhibitor of normal sleep.


The Influence Of The Limbic System


Finally, Patrick Wood, M.D., may be the closest to explaining a role for dopamine in fibromyalgia.24 While most of the researchers mentioned do not necessarily agree with each other, I find validity in each of their messages. Wood contends that dopamine and dopamine sub-receptors inherently control a variety of important limbic functions with respect to the stress response.

The limbic system is in the central brain, near the pituitary and above the brainstem structures containing the stimulatory portion of the autonomic nervous system. Fibers leaving the locus ceruleus, which generates autonomic arousal, must pass through the limbic system to have a physiologic effect. As gatekeeper of the autonomic nervous system, the limbic system may be very important.

Clearly, pramipexole has a positive effect for fibromyalgia based on the recent study to be published later this year. Its manufacturer believes that it is dopamine receptor specific.

The clinical response suggests that arousal is decreasing, and sleep and fibromyalgia symptoms are improving with an increasing pramipexole dose. But, there are no D3 receptors in the brainstem where the autonomic arousal is generated. How does pramipexole work if there are no receptors for it in the brainstem?

Wood explains that the limbic system is rich with dopamine receptors, including D3. In rats, low doses of pramipexole feed back on the neurons to decrease their firing and physiologic effects.6 In the limbic system, this would mean that limbic neurons would become less functional at low pramipexole doses.

As a gate for brainstem arousal, the gate would be left wide open. Arousal would go unchecked, and excessive autonomic stimulation could wreak havoc on sleep and other autonomically controlled functions in the skin, blood vessels, bowels, bladder, etc.

Higher pramipexole doses in rats do the opposite. As the concentration at the neuron increases with increasing dose, postsynaptic neurotransmission is favored over presynaptic transmission.

In other words, higher pramipexole concentration increases limbic function to block the brainstem arousals and let one sleep. This central limbic control might also be expected to reverse the other autonomic problems faced by patients with fibromyalgia, such as irritable bowel, irritable bladder, abnormal sweating, and temperature regulation and palpitations.


Dopamine And The Symptoms of Depression


The theories emerging from the consideration of dopamine may also turn the table on psychiatric disease. In contrast to believing fibromyalgia to be a psychiatric disease, unraveling fibromyalgia, autonomic regulation and dopamine regulation may begin to explain psychiatry. Anxiety is a fight-or-flight reaction, and a panic attack is a poorly regulated survival instinct.

Regulation of autonomic arousal is fundamental to the symptomatology of fibromyalgia, the nature of stage III/IV sleep deprivation and an avenue to better options for and understanding of stimulatory psychiatric disorders.

It is not surprising that panic disorder, anxiety disorder, and post-traumatic stress disorder are very common in patients with fibromyalgia. Is there an underlying thread of autonomic dysregulation among them? Certainly, controlling excessive autonomic arousal or the fight-or-flight response would be expected to decrease the intensity of anxiety and panic symptoms.

Also, in a blinded clinical trial comparing pramipexole to fluoxetine to placebo in patients with depression, pramipexole was superior.25 The 20 mg fluoxetine dose and the 1.0 mg pramipexole dose were equally effective and superior to placebo, but the 5.0 mg pramipexole dose was superior to fluoxetine in controlling depressive symptoms.

Interestingly, this is nearly the dose tested for treatment of fibromyalgia (4.5 mg). How dopamine affects depression is beyond the scope of this article, but the autonomic effects of pramipexole may also have relevance to depression.

Only additional rigorous research will explore these questions adequately, but it will not be surprising if dopamine ultimately surpasses serotonin in press coverage and clinical interest.

Parkinson’s disease teaches an important lesson for those with ‘mysterious and unproven’ diseases. If we keep our eyes open, we may find answers in unexpected places.


References


1. Vallone D, Picetti R, Borrelli E. Structure and function of dopamine receptors. Neurosci Biobehav Rev 2000 Jan;24(1):125-32.


2. Bennett RM. Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia. Mayo Clin Proc 1999 Apr;74(4):385-98.


3. Bennett RM, Kamin M, Karim R, Rosenthal N. Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med 2003 May;114(7):537-45.


4. Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of Fluoxetine and amitriptyline for the treatment of Fibromyalgia. Arthritis Rheum 1996 Nov;39(11):1852-9.


5. Holman AJ, Myers RR. Treatment of Fibromyalgia Syndrome with the Dopamine 3 Receptor Agonist Pramipexole: A Double-blinded, Randomized, Placebo-controlled Trial. Arthritis Rheum 2004;50(12): L20.


6. Dziedzicka-Wasylewska M, Ferrari F, Johnson RD et al. Mechanisms of action of pramipexole: effects on receptors. Rev Contemp Pharmacother 2001;12:1-31.


7. Holman AJ, Neiman RA, Ettlinger RE. Preliminary efficacy of the dopamine agonist, pramipexole, for fibromyalgia: the first, open label, multicenter experience. J Musculoskeletal Pain 2004;12(1):69-74.


8. Holman AJ. Safety and Efficacy of the Dopamine Agonist, Pramipexole, on Pain Score for Refractory Fibromyalgia. Arthritis Rheum 2000;43(9)suppl:A1599.


9. Holman AJ. Pramipexole and fibromyalgia: promise and precaution. [letter] J Rheum 2003;30(12):2733.


10. Holman AJ. Treatment of Fibromyalgia with the Dopamine Agonist Ropinirole: a 14-week Double-blind, Pilot, Randomized Controlled Trial with 14-week Blinded Extension. Arthritis Rheum 2004;50(9)suppl; A1870.


11. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990 Feb;33(2):160-72.

12. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculoskeletal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects. Psychosom Med 1975;37:341-351.

13. Moldofsky H, Scarisbrick P. Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosom Med 1976;38:35-44.

14. Martínez-Lavín M, Hermosillo AG, Rosas M, Soto M. Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart variability analysis. Arthritis Rheum 1998;41(11):1966-71.

15. Yunus MB, Masi AT, Aldag JC. A controlled study of primary fibromyalgia syndrome: clinical features and association with other functional syndromes. J Rheumatol Suppl 1989 Nov;19:62-71.

16. Yunus M, Aldag J. Restless legs syndrome and leg cramps in Fibromyalgia syndrome: a controlled study. BMJ 1996;312:1339.

17. Older SA, Battafarano DF, Danning CL, Ward JA, Grady EP, Derman S, Russell IJ. The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlation with insulin-like growth factor I. J Rheum 1998;25(6):1180-6.

18. Lentz MJ, Landis CA, Rothermel J, Shaver JL. Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women. J Rheumatol 1999;26(7):1586-92.

19. Holman AJ. Effect of Lorazepam on Pain Score for Refractory Fibromyalgia. Arthritis Rheum 1998;41(9) Suppl:A1359.

20. Holman AJ. Safety and Efficacy of Lorazepam for Fibromyalgia after One Year. Arthritis Rheum 1999;42(9)suppl:A385.

21. Lin SC, Kaplan J, Burger CD, Fredrickson PA. Effect of pramipexole in treatment of resistant restless legs syndrome. Mayo Clin Proc 1998 Jun;73(6):497-500.

22. Ondo W. Ropinirole for restless legs syndrome. Mov Disord 1999 Jan;14(1):138-40.

23. Crofford LJ, Young EA, Engleberg NC, Korszun A, Brucksch CB, McClure LA, Brown MB, Demitrack MA. Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome. Brain Behav Immun 2004 Jul;18(4):314-25.

24. Wood PB. Fibromyalgia syndrome: a central role for the hippocampus--a theoretical construct. J Musculoskeletal Pain 2004;12(1):19-26.

25. Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 2000;11(2):58-65.




[This Message was Edited on 01/12/2008]
[This Message was Edited on 01/15/2008]
 

jennbug

New Member
I have tried levo- dopa, pramipexole and now ropinirole all with much success. The trouble is that well they all help me so much they have negitive side affects. More research needs to be done. This is just the begining and for that Iam greatful.
jenn.
 

PVLady

New Member
I wish the cause of our conditions could be treated, not just the symptoms. My dad had Parkinsons and it makes me wonder if I will wind up with it also.
 

mammabek

New Member
this is exactly what i was trying to explain when i said that my childhood trauma induced me to stay awake at night in fight or flight mode so many times that it eventually "reworked" my hypothalamus and i firmly believe dopamine is the key to "my" cure. i quit having a lot of my "generalized " pain when i started taking miripex, my irritable bowel and bladder both disappeared (except three times when i was under extreme stress) then doc put me on lyrica too, believing all the hype. i felt next to cured for 3 months. then she asked me to take xanax for what she called bed anxiety (mind racing, like described above) with in 2 days i was bedridden again. i have come off the xanax, after finding someone on the board who told me about the xanax and am slowly getting bett. i am also coming off the lyrica..too much weight gain i had same improvement just with miripex, without side effects...thank you again, maybe now people will quit calling some of us psychologizers!
blessing to u pvlady and a pain free day!
 

HurtsToMove

New Member
will be the next big drug, IMO. It had DEFINITELY helped my pain when nothing else seemed to work. I firmly believe that our brain chemicals are out of whack (for whatever reason) and need adjusting. The trick is finding the right meds at the right dosage to balance those neurotransmitters. You need to work on serotonin, norepinephrine, and dopamine.
 

PVLady

New Member
I may discuss Mirapex with my doctor. Thanks for the feedback, it really helps to hear others experiences.

 

HurtsToMove

New Member
Here's more Mirapex info to take to your doctor, from Journal of Arthritis & Rheumatism, August 2005:

A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications

Andrew J. Holman *, Robin R. Myers
Pacific Rheumatology Associates, Renton, Washington


*Correspondence to Andrew J. Holman, Pacific Rheumatology Associates, 4300 Talbot Road South, Suite 101, Renton, Washington 98055

Abstract

Objective
To assess the efficacy and safety of pramipexole, a dopamine 3 receptor agonist, in patients with fibromyalgia.

Methods
In this 14-week, single-center, double-blind, placebo-controlled, parallel-group, escalating-dose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening. The primary outcome was improvement in the pain score (10-cm visual analog scale [VAS]) at 14 weeks. Secondary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Health Assessment Questionnaire (MDHAQ), the pain improvement scale, the tender point score, the 17-question Hamilton Depression Inventory (HAM-d), and the Beck Anxiety Index (BAI). Patients with comorbidities and disability were not excluded. Stable dosages of concomitant medications, including analgesics, were allowed.

Results
Compared with the placebo group, patients receiving pramipexole experienced gradual and more significant improvement in measures of pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased 36% in the pramipexole arm and 9% in the placebo arm (treatment difference -1.77 cm). Forty-two percent of patients receiving pramipexole and 14% of those receiving placebo achieved 50% decrease in pain. Secondary outcomes favoring pramipexole over placebo included the total FIQ score (treatment difference -9.57) and the percentages of improvement in function (22% versus 0%), fatigue (29% versus 7%), and global (38% versus 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend for pramipexole treatment than for placebo, but failed to reach statistical significance, including improvement in the tender point score (51% versus 36%) and decreases in the MDHAQ psychiatric score (37% versus 28%), the BAI score (39% versus 27%), and the HAM-d score (29% versus 9%). No end points showed a better trend for the placebo arm. The most common adverse events associated with pramipexole were transient anxiety and weight loss. No patient withdrew from the study because of inefficacy or an adverse event related to pramipexole.

Conclusion
In a subset of patients with fibromyalgia, 50% of whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well-tolerated.

Link to full article: http://www3.interscience.wiley.com/cgi-bin/abstract/110575103/ABSTRACT?CRETRY=1&SRETRY=0


[This Message was Edited on 01/15/2008]
 

grace54

New Member
My earliest fibromyalgia books spoke of the problem being mainly a dysfunction of the central nervous system. Also pain is always interrepted in the brain so when someone says its in your head they are unknowingly not that far off except if they mean you are somehow crazy or making it up.

It is also noteworthy that it doesn't take that long for fibro to set in with interrupted sleep as that and chronic stress changes are brain chemicals. Most descriptions of causes of fibro will include some type of trauma, whether physical or emotional.

I know from my own experience my brain chemicals were so far off I lived in a state of major depression so that it was painful to think.Even today if I have a sleepless night I will pay for it with depression and more pain. It has nothing to do with babblling it has all to do about the science of chemicals in our system that keep us functioning normally if the body gets what it needs.
 
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