Again and Again

Again and Again



Neuroscientists Uncover The Pain Source Of Fibromyalgia Fibromyalgia, a debilitating, chronic pain that runs from the neck to the shoulders to the lower back to the hips to the knees and affects millions of people world wide, especially women, is not an ‘imaginary illness’ scientists have discovered. Doctors were convinced that Fibromyalgia was more an imaginary and psychological disorder than an actual physical ailment. Breakthrough research shows that the illness is not imaginary and is actually caused by an excess of nerve fibers in the blood vessels. Fibromyalgia actually means “pain in connective tissue and muscles” and people who suffer from the illness report a variety of symptoms that occur at the same time: body pain, headache, sleeplessness, stomach problems and stiffness. Fibromyalgia symptoms American neurologists made the discovery when they tested the hands of non-sensory individuals by pricking a needle into their skin. They then repeated that process with people who claimed to suffer from Fibromyalgia and found that an exaggerated amount of a specific nerve vessel known as ‘Arterial Venules (AV)’ responded to the pricking. Up until this discovery, scientists were convinced the AVs were strictly responsible for controlling blood flow in the blood cells. But now the researchers know that there is a direct link between the nerve endings and widespread body pain. The study also explains why people suffering from Fibromyalgia have extremely oversensitive hands and other tender areas on the body. Thanks to the breakthrough discovery, scientists are now hopeful they can develop treatment and possibly a cure for the illness. Source: Pain Medicine, May 20, 2013. By Phillip J. Albrecht PhD, Quanzhi Hou MD PhD, Charles E. Argoff MD, James R. Storey MD, James P. Wymer MD PhD, and Frank L. Rice PhD. Integrated Tissue Dynamics, LLC, Rensselaer, New York, USA; Center for Neuropharmacology & Neuroscience, Albany Medical College, Albany, New York, USA.

Spasm Chasm


Deep within a dark dank place, hidden from the human race.

I sit.

I feel alone.

The pain is deep and winding.
My muscles ache and twitch.
No drugs flow through my veins.
If they did, they’d only make me itch.

These oddities often manifest, quite simply on their own.

My legs are locked, my arms are torn, it even hurts to smile.
A locked jaw, I want no more, I’m no longer mobile.
A sudden jerk of pre convulsion, pain of mind without emotion.
A limb, my face, but no trace, left for anyone to see.

The abyss of fibres rip, without sound, people pass by unnoticeably.

The Spasm Chasm I not implore, consumes all of my being.
Although I feel it deep within, it’s not for all, too seeing!
On my own, I sit at home, without choice or empathy.
I really want this to end, it’s been like this days.

When will it end?
Will I mend?

My body, convolutes, a random dance.

Confusion of verse betrays me, Fibro Fog, belated me.

The mountain of stairs, not that there’s many, is simply to hard to climb.
It’s times like these that make me ache, with throbbing and pulsation.
Pins like bladed needles walk my back, where art though compassion oh great creator.
My words like medicine heal my soul, the Spasm Chasm has its hold.

This verse, full of gaping, nonsensical confusion.
This is how the Spasm Chasm consumes you!

My world, its illusion.

By Stuart Otway-Smith

An attempt to describe in poetry what Muscle Spasms feel like, a symptom of Fibromyalgia / Chronic Pain Syndrome.

National Fibromyalgia & Chronic Pain Association
Mark the date for May 12 National Fibromyalgia Awareness Day!

Day Fifityfive:

Restless sleep makes you really pissed off for the want of better words.

Im’ so tired…

I struggled to make a cup of coffee this morning and dropped my cup on the floor, it smashed to bits, then in a frivolous fury of frustration; I grabbed the coffee jar and slammed it into the floor, the glass shattered in all directions and the brown coffee granules ejected all over the room.

What a mess!


Shell has been off with me for days, I am really feeling the pressure of trying to be nice on the outside when you’re dying from within.

Maybe there is hope after all, Shell just sent me a text and usually I keep those things private but there are exceptions to the rule right?

She said:

I love you so very much, I feel your pain but don’t know how to take it away or how to comfort you.

I feel you are slipping away from me more each day and that scares me.

I try to hold you, Tell you I love you, I must find another way to bring you back to me.

That bond between us was like a rope that keeps pulling us back together, the rope has worn thin and frayed.

I must strengthen the rope and not let it break like string.

I know you feel our love is held together by cobwebs, but know that cobweb is one of the strongest materials known to us, if we keep puling on the rope together in the same direction we will be able to get closer to each other and tie a knot, rather than tormenting each other in a bitter tug of war.


I got a very special message from a very special person, no names sorry! They know who they are.

It said: (slightly modified for privacy)

I don’t blame you, I did not mind as I still read everything everyday , it seems like your depression is getting worse and I don’t want that for you. I know what Shell did was wrong and I can only imagine what you are feeling but look how far you have come over the past 16 years, you CAN get through this.

You both need to enjoy each other no matter how much it hurts at the moment.

I know you love Shell very much and I know she does make mistakes, trust me I’ve been through some of them with her too; I have to keep saying, think about the kids! Because it rubs off on them especially at the age they are at, I don’t want them to feel down too.

By what I’ve been told about Shells dates speaking to her, it sounds to me that the baby is defiantly yours, so forget about everything else and shut the world out, you and Shell have a baby on the way and your little family is all that matters now.

Go and hug her even if it hurts you and tell her you love her give her, a little positive note and say that you know that you can get through it.

Then I want you to go and hug the kids and tell them you love them and that your sorry for being down lately and that your going to change that.

You may not think it at the moment but they need you now more than ever trust me.
I don’t know what I would do without my Dad.

Please  just think to the future and not what has happened in the past, remember you can’t change that.

I love you Xxx

I hope you don’t mind me posting that message although modified ever so slightly as you know.

I love you to and thank you for caring and passing me a hand via words that I see with my eyes and feel in my heart.

I will do exactly as you suggest, today more than any other due to the tension it would make the biggest difference and liven up every bodies day, you really are a wonderful person and I am truly grateful and blessed to be apart of your life.

Thank you again for telling me just what I needed to hear, in such a sweet way.

It’s still early enough to finish the day off nicely.

As I finish this sentence the Sun has just yawned out loudly and appears in the garden gently erasing the rain clouds.


Although I am in a huge amount of pain and lethargy reminds me so, we have had a reasonable day today, it didn’t start to good with my mouth ranting despicable torment for a short while after the coffee incident. Since then we have started to get close again, closer than we have been for some days. I’m pleased for Shells message, a simple use of words to let me know she is hanging on to our relationship, I to will not let it go, I love you far too much to let it hang out to dry.

I guess this is apart of the process of healing from such pain.


I listen to Red Sky at Night from the album On An Island by David Gilmour and write how I feel.

Why is it every time I go out of my way to be divinely nice, treat Shell with the utmost respect that she deserves, make her happy by going out of my way to really love her, I screw it all up with my mouth?


I love you sweetheart, saying that now after what I just said to you makes the words feel dry.

I wish my mouth would just STFU and stay with the loving kindness, I truly feel in my heart and mind.

Why do I seem to have this primal urge to just rant at you randomly in a fit of rage and venom?

Please understand that what I say is a result of the bad images in my mind I do not mean any of it especially about the baby not being mine, what a horrible person I am, how dare I make you feel like that, especially when pregnant.

I want to rip my head off and hammer it to my arse as just as things got better I let rip at Shell making her whimper in tears.

I’m sorry for acting childish and immature, and saying all that rubbish to you and the fact the kids heard my outrage saddens me deeply.

Bad person I feel, Bad person I am, mistakes I have not learned from, but I am just a man.

I love you Shell with every part of my soul, life with you is my destiny, if only I would realise it.

I burned the rope you tossed me before I even had a chance to catch it this evening, please I’m begging you, throw me another one, I promise not to ever let it go.

It was me that caused the resentment and hate tonight not you, you have tried so hard and I thank you with all of my being.

Please forgive me, my love, as now I really need to learn to forgive myself for ventures past and failed memories.

Dr. Steven Yen on Fibromyalgia Trigger Points (Interview)

Dr. Steven Yen on Fibromyalgia Trigger Points (Interview)

Dr. Steven Yen of Natural Fibromyalgia Treatments explains what fibromyalgia trigger points are, and some of the ways these can be treated.

Dr. Steven Yen has been treating fibromyalgia naturally, without the use of drugs or surgery for patients in his private practice since 2002.

Natural Fibromyalgia Treatment blog:

More about Dr. Yen:…

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Other FREE Pain Relief resources:

Fibromyalgia Awareness

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Day Fortynine:

I am really getting behind with my progress but today is back on track XD.

Got up quite late today at around lunchtime, Shell had a private first appointment with a midwife as the topics to be discussed where not things I wanted to hear due to the affair, on a positive note everything is going well thus far although the literature and information Shell came home with from the midwife scared the life out of me.

Apparently due to her age she has a higher chance 1 in 105 of down syndrome and very soon we will be able to scan the baby to make sure everything is okay.

I have had a lots of bad images in my mind today of Shell and Darren, I am reframing them all and they are not hurting anywhere near as much, especially after our conversation we had recently about how used and abused she feels about the way he treated her.

She has not opened up to me before about this and I am pleased that she has, I know it is painful for me to hear her explain how he made her feel, she said that she felt disappointed she thought he was her friend, she felt disgusted, abused and that he is not the person she thought he was, but a person who’s only concerns where his own self pleasure and jealously of what we have.

In a way I wish I had never asked, but Shell has been more peaceful today I think that she really needed to let go of her hate for Darren as he clearly hurt her as well as everyone else purely due to his own selfishness.

Due to the nature of things she has had to have STI, and full blood work tests, results to follow!

I love you Shell with all my heart and soul and thank you for yesterday as we had a perfect day of loving kindness with the family and I look forward to many more of them in the future.


Shell has left to go back to the doctors as the midwife suggested she have a quick check-up.


I have just had a turbo and wow that feels good, Shell has been looking after me today as I am feeling low and due to the dank weather my body aches.

I just looked out of the window and noticed the sun rise above the clouds, fantastic I am going to sit in the garden in a while and just relax and be at one with nature.

Shell just got back, I keep bursting into tears today, I am not saying anything hurtful and am keeping the vengeance inside of my mind as after such a perfect day yesterday I do not want to spoil it.

Doctors kill thousands due to ‘death tables,’ Utah expert says in new study

Reference tool responsible in death toll from prescription painkillers

A pill box with various medications in it.

SALT LAKE CITY — A standard reference tool used by the medical profession is so inaccurate that doctors across the country are accidentally killing patients by the thousands each year, according to an expert in Utah who co-authored a disturbing new study.

The study found that the faulty reference tool is responsible for a significant portion of the growing death toll from prescription painkillers.

“I think it could be thousands, nationally, for sure,” said Dr. Lynn Webster of Lifetree Clinical Research in Salt Lake City. He believes dozens of Utahns die each year for the same reason.

At issue are so-called “equianalgesic conversion tables.” Physicians use the tables to calculate the proper dose when a patient is switching from one “opioid” painkiller to another. The tables display equivalent doses of various drugs.

“They’re notoriously inaccurate,” Webster said. “In fact, I call them ‘the death table.'”

Webster and Dr. Perry G. Fine of the University of Utah co-authored the new study, which is a review of medical literature and forensic reports from around the country. It’s published in the April edition of Pain Medicine, the official journal of the American Academy of Pain Medicine.

The study may cause a stir because of the prominence of the two researchers. Fine is immediate past-president of AAPM and Webster is the organization’s president-elect.

“We’ve been taught that these equal analgesic tables are reasonably safe, as a guide,” Webster said. “And they’re not.”

Patients who need pain medication frequently switch from one drug to another. Doctors often prescribe a change because of side-effects such as nausea. Patients also switch drugs because they develop a tolerance for a given painkiller or because insurance companies won’t continue covering an expensive drug.

The prescribing physician typically figures out the proper equivalent dose by consulting the published conversion tables.

They’re often flat wrong, according to Webster.

“And that’s why we’re basically on a campaign nationally to make sure that every physician who prescribes an opioid understands they can’t use these conversion tables,” he said.

Nationally, an estimated 15,000 people die each year from overdoses of opioid pain medicine. That includes such familiar painkillers as Oxycontin, oxycodone, Percocet, morphine, and methadone.

“A lot of the deaths have been attributed to using these conversion tables and starting patients on too high of a dose,” Webster said.

“Methadone is the riskiest,” he said, but all the opioids can be deadly if the prescribing physician gets the dosage wrong.

He emphasizes that it’s not just drug addicts and long-term patients who are at risk.

“It could be somebody who’s been on pain medication after a hip operation or a knee operation for several weeks and it’s not working any more,” Webster said. When a physician uses the conversion tables to estimate the proper dose, “It could be very far off from what’s safe.”

As a solution to the problem, Webster recommends that a prescribing physician gradually phase in the new drug instead of abruptly switching from one to the other. He said the original dose should be reduced by 10 to 30 percent while the new drug is used at the lowest available dose. Then the original drug should be reduced by 10 to 25 percent each week while the new drug dosage is gradually increased.

Webster says physicians share the blame for the situation with the U.S. Food and Drug Administration and pharmaceutical manufacturers which encourage doctors to use the conversion tables.

“We came up with these estimates about how to determine what would be safe,” Webster said, “but they’re really not scientifically based.”


I can honestly say that I have nearly died twice just in the last year from overdoses that where prescribed to me by a doctor visiting my home.
A simple overdose of medication took me to the hospital as I hadn’t slept for four days solid and had a constant migraine throughout, upon arriving at the hospital they said if I had slept I would have probably died.

On the other occasion a visiting doctor gave me some neurotriptaline, sorry for the spelling.
I again ended up in accident and emergency this time with serotonine syndrome a deadly near death experience was had that day.

There must be tens of thousands of people dying each year from pharmaceuticals.

Namaste, Stu.

Neurobiology Underlying Fibromyalgia Symptoms

Review Article

Neurobiology Underlying Fibromyalgia Symptoms

1Alan Edwards Centre for Research on Pain, McGill University, 3640 University Street, Room M19, Montreal, QC, H2A 1C1, Canada
2Department of Neurology & Neurosurgery, McGill University, 3640 University Street, Room M19, Montreal, QC, H2A 1C1, Canada
3Department of Anesthesia, McGill University, 3640 University Street, Room M19, Montreal, QC, H2A 1C1, Canada
4Center for Neurosensory Disorders, University of North Carolina, CB No. 7280, 3330 Thurston Building, Chapel Hill, NC 27599, USA

Received 27 April 2011; Accepted 23 August 2011

Academic Editor: Muhammad B. Yunus

Copyright © 2012 Marta Ceko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that include cognitive and sleep disturbances, and other abnormalities such as increased sensitivity to painful stimuli, increased sensitivity to multiple sensory modalities, and altered pain modulatory mechanisms. Here we relate experimental findings of fibromyalgia symptoms to anatomical and functional brain changes. Neuroimaging studies show augmented sensory processing in pain-related areas, which, together with gray matter decreases and neurochemical abnormalities in areas related to pain modulation, supports the psychophysical evidence of altered pain perception and inhibition. Gray matter decreases in areas related to emotional decision making and working memory suggest that cognitive disturbances could be related to brain alterations. Altered levels of neurotransmitters involved in sleep regulation link disordered sleep to neurochemical abnormalities. Thus, current evidence supports the view that at least some fibromyalgia symptoms are associated with brain dysfunctions or alterations, giving the long-held “it is all in your head” view of the disorder a new meaning.

1. Introduction

In order to examine the neurobiology underlying the symptoms of fibromyalgia, we must first determine what those symptoms are. Until recently, fibromyalgia (FM) was diagnosed based on the ARC1990 criteria [1], which were widespread pain in combination with tenderness at 11 or more of 18 specific tender point sites. The provisional ACR 2010 FM diagnostic criteria [2], suggested as an alternative method of diagnosing FM, do not require the presence of tenderness, but rather include a list of several other symptoms, including fatigue, unrefreshing sleep, and cognitive symptoms, as well as a mix of some other symptoms that could include headache, depression, and lower abdominal pain/cramping. The hallmark symptom is still widespread pain, and a diagnosis of fibromyalgia requires this symptom. However, a patient must also have some of the other symptoms that are common among FM patients in order to reach a composite score that would lead to a diagnosis of FM. In addition to clinical symptoms that make up the diagnosis of FM, experimental studies have identified a number of other abnormalities in FM patients, including increased sensitivity to multiple types of painful stimuli, increased sensitivity to other sensory modalities, and alterations in pain modulatory mechanisms. Further, neuroimaging studies have found functional, anatomical, and neurochemical differences in the brains of FM patients compared to healthy control subjects. Most of the clinical symptoms associated with FM have not been systematically studied in the experimental setting, but there are a number of studies that have provided an objective evaluation of the altered cognitive functioning and sleep disturbances reported in FM patients. Thus, this paper will focus on the experimental evidence related to FM symptoms and connect these perceptual and cognitive signs to abnormalities observed in the brains of FM patients.

1.1. Altered Pain Perception in FM Patients

The hallmark symptom of FM is widespread ongoing musculoskeletal pain. In addition, FM patients have been distinguished from other patients with widespread pain syndromes primarily by the presence of tenderness that has been assessed clinically by finding pain evoked by 4 kg manual pressure in at least 11 of 18 defined tender points. This tender point concept was not based on an understanding of the underlying pathophysiology, but rather on empirical observation. Thus, although the ARC-90 diagnostic criteria provided an important uniform tool for defining the FM syndrome, they did not validate the tender point concept, due to the circular evidence on which the criteria were based [3]. In fact, much evidence indicates that tender points are just sites normally more sensitive to pressure pain in all individuals [47] and that FM patients have an increased pressure sensitivity at non-tender-point sites as well [8]. Accumulating evidence now shows that FM patients have increased sensitivity to many types of painful stimulation, including pressure at non-tender-point sites [9], heat and cold pain [6,1014], electrical stimulation [6], and intramuscular hypertonic saline injection [15]. Despite the plethora of evidence for hypersensitivity to painful stimuli, there is less evidence that FM patients are more sensitive to innocuous somatosensory stimuli. Detection thresholds for tactile and electrical stimuli are not altered in FM [61213], but Hollins et al. [16] found that FM patients rated innocuous pressure as more intense than did healthy controls, although the effects in the innocuous range were weaker than in the noxious range. The evidence for changes in cool or warm detection also is mixed, with most investigators finding no differences between FM and controls for heat [610] or cold [1012], whereas one study found FM patients to have reduced heat detection thresholds [12], and one study found patients to have reduced cold detection thresholds [6]. Thus, it appears that the altered sensitivity within the somatosensory system is more profound in the noxious range than in the innocuous range.

1.2. Evidence for Generalized Hypersensitivity to Unpleasant Stimuli

The hypersensitivity of FM patients to painful stimuli has led some investigators to propose that fibromyalgia involves a hypervigilance to pain and pain-associated information [1719]. However, there is now evidence that the hypersensitivity to unpleasant stimuli extends beyond the somatosensory system, which has led to the hypothesis that there is a generalized hypervigilance for sensory stimuli in FM [162021]. A few studies have examined the sensitivity of FM patients in modalities other than pain and found perceptual amplification. FM patients have been shown to have decreased tolerance of unpleasant noise [20] and increased sensitivity to loud unpleasant auditory stimuli that parallels their increased pressure pain sensitivity [22]. Similarly, FM patients perceive unpleasant olfactory stimuli to be more intense and more unpleasant than do matched control subjects [23]. On the other hand, when pleasant odors were tested, FM patients and controls perceived the odors as equally intense, consistent with another evidence that the hypersensitivity across perceptual modalities may be confined to stimuli in the unpleasant range [24]. Nevertheless, for pleasant odors, although FM patients did not rate them as more intense, they did evaluate the pleasant odors as less pleasant than did control subjects. Further, a range of auditory stimuli were rated as more intense by FM patients than by controls, and auditory stimuli rated as mildly pleasant by healthy subjects were rated as somewhat unpleasant by FM patients [16]. The finding of hypersensitivity in multiple modalities of stimulation, particularly for unpleasant stimuli, suggests that the evoked pain sensitivity of FM may be related to an altered hedonic appreciation for sensory stimuli, rather than to peripheral tissue abnormalities.

1.3. Other Phenomena Related to Altered Pain Perception

Other types of evidence from experimental pain studies in FM patients support the idea of a centrally mediated up-regulation of nociceptive activity in the CNS. A central pathophysiological process that appears to be disturbed in FM patients is the “windup” of central nociceptive processing of C-fibre input to the spinal cord, resulting in the perceptual phenomenon of temporal summation of pain. Windup of nociceptive activity is dependent on activation of the NMDA receptor complex in the spinal cord by input from C-nociceptors [2526]. Some FM patients show increased temporal summation of pain and increased aftersensations at the termination of noxious stimulation [27]. These enhanced responses could be related to one or more of several possible factors: (1) an ongoing peripheral source of input from C nociceptors other than the applied stimulus; (2) sensitized NMDA receptors on central nociceptive neurons; (3) abnormalities in descending modulation; (4) abnormal processing at supraspinal levels. Evidence of increased sensitivity in multiple sensory modalities suggests that ongoing C-nociceptor input cannot alone account for FM symptoms, indicating that there probably also are either sensitized NMDA receptors, abnormalities in modulatory systems in the brain, or abnormal sensory processing at spinal or supraspinal levels. Increased sensitivity has been demonstrated at the spinal level in FM [11]. Staud et al. [28] showed that an NMDA inhibitor reduced temporal summation in both healthy people and FM patients, suggesting that NMDA receptors probably are not sensitized in FM. On the other hand, experimental evidence shows that there are abnormalities in pain modulatory systems in FM patients that could account for altered temporal summation and other putative spinal effects.

1.4. Altered Pain Inhibition in FM Patients

For hundreds of years, clinicians have known that pain inhibits pain, a phenomenon termed “counterirritation.” More recently, a physiological basis of this phenomenon has been identified; the application of noxious stimulation activates an endogenous analgesic system involving supraspinal descending control of dorsal horn nociceptive activity. This system is termed “diffuse noxious inhibitory control” or DNIC and its physiological basis in the spinal cord has been studied extensively in anesthetized animals [2930]. Nevertheless, when competing noxious stimuli are presented in conscious humans, other systems that modulate pain, such as distraction, also are probably in effect, so that care must be taken in inferring that perceptual effects are due to DNIC. Accordingly, a group of interested researchers has suggested that the term “conditioned pain modulation” be used in humans studies to avoid the mechanistic implication [31]. Studies that have examined conditioned pain modulation in FM patients show that conditioning stimuli that produce an analgesic response to experimental pain stimuli in healthy control subjects fail to have an effect on FM patients [133234]. One of these studies controlled for the effects of distraction and habituation and found a similar lack of conditioned pain modulation in FM patients [33], suggesting the possibility that the DNIC system is in fact impaired in these individuals. Alternatively, DNIC and other descending inhibitory systems could be activated by the widespread pain of FM, and the failure to demonstrate DNIC in FM could represent a ceiling effect in which these activated systems cannot be further engaged by the experimental manipulations [8]. In addition, distraction can have a powerful pain-inhibiting effect [3539], and some researchers have suggested that FM patients have altered attentional focusing, with a hypervigilance to unpleasant stimuli (see discussion above).

2. Other Symptoms of FM

2.1. Altered Cognitive Function in FM Patients

In addition to pain, many patients with fibromyalgia complain of problems with memory and concentration, often referred to as “fibrofog” [4043]. This clinical symptom has received a large amount of experimental study, and studies using objective cognitive tests substantiate patients’ subjective reports of cognitive dysfunctions, most commonly related to speed of information processing, attention, and memory [4356]. The most robust deficits in tests of memory and attention have so far been observed in paradigms involving a prominent distraction from a competing source of information, wherein FM patients are less capable than healthy controls to retain new information when rehearsal is prevented by a distraction [495057]. Milder deficits have been observed in memory free of distraction at encoding [43444849515859]. FM patients frequently display greater impairments in the ability to actively retrieve past episodic events in the absence of a cue (free recall) than on recognition tests, which serve to evaluate the retrieval of remembered information and are more resistant to the effects of impaired attention and concentration [43444851]. It has thus been proposed that memory impairments in FM are more highly related to attentional factors that modulate the efficiency of memory functioning than to primary memory processes per se [486061]. Thus, the inability to manage distraction seems to be a particular problem in fibromyalgia patients and is reflected in patients’ reports of difficulty concentrating and dealing with complex, rapidly changing environments [61] and by memory tests showing performance decrements in the presence of distraction. Impaired cognitive performance is evident even after controlling for anxiety and depression and the influence of medications that might affect cognitive functioning [43505258]. Another area of cognitive functioning that has been shown to be abnormal in FM is that of emotional decision making [6263]. A similar deficit has been shown in chronic back pain patients, suggesting that this is not unique to FM [64].

2.2. Sleep Disturbances in FM Patients

Many FM patients complain of unrefreshed sleep. Several laboratory studies using objective measures of sleep physiology such as EEG substantiate these reports by showing disordered sleep architecture in FM patients, including delayed onset to sleep, altered sleep stage dynamics, and reduced slow wave sleep (deep sleep) and rapid-eye movement (REM) sleep [6568]. The intrusion of EEG frequencies characteristic of wakefulness (alpha waves) in the deep non-REM sleep (delta waves) seems to be a prominent feature of the nonrestorative sleep of FM patients [656971]. Further, patients with FM often have fragmented sleep resulting from periodic intrusions such as involuntary limb movements (restless legs), sleep apnea, and arousal disturbances [687274]. Although FM patients tend to report greater disturbances in sleep duration and quality than shown in laboratory studies, and their subjective reports correlate better with the severity of clinical symptoms [75], objectively measured sleep disturbances have been associated with pain and subjective daily sleepiness in several studies [6768,7173].

3. Brain Changes That Could Underlie Symptoms

3.1. Neural Basis of Pain Amplification and Altered Pain Modulation

Functional brain imaging studies support psychophysical findings of increased pain perception in FM, in that there is an augmentation of sensory processing throughout pain-related brain regions [97681]. This is important, since laboratory findings of increased sensitivity could be interpreted as a reporting bias, rather than evidence of increased activation in pain pathways. The functional imaging studies have found that fibromyalgia patients show significantly more activity in response to pressure and thermal stimuli compared to controls in a number of brain regions. Increased activations were observed not only in limbic structures, but also in brain regions involved in sensory-discriminative processing, such as primary and secondary somatosensory cortices, which supports the view that neural responses to afferent signals are amplified in fibromyalgia.

Although the increased pain-evoked brain activations corroborate patients’ reports, the correlation between increased brain activity and increased pain perception does not explain how the afferent signal is amplified. As discussed above, there is psychophysical evidence of dysfunctions in pain modulation as well as pain perception. There is now much evidence that the activation of descending control circuitry is involved in pain modulation and that this circuitry includes parts of prefrontal, cingulate, and insular cortices [2336378283]. A number of anatomical imaging studies in FM patients reveal decreased brain gray matter in these regions [8490]. Although the cellular basis of decreased gray matter in FM patients is not known, it is possible that due to neuronal loss, decreased dendritic arborisation, or changes in glial activation, pain inhibitory systems do not work in FM patients as well as in healthy individuals.

Consistent with the idea that pain modulatory systems may be disturbed in fibromyalgia are data showing that some FM patients have abnormalities in neurochemical systems involved in pain control, including the forebrain opioid and dopamine systems. A positron emission tomography (PET) competitive binding study using the D2/D3 receptor antagonist [11C] raclopride showed that striatal dopamine is released in response to painful muscle stimulation in healthy subjects, but not in FM patients [1591], which might partially explain the increased sensitivity of FM patients to the painful muscle stimulation. For the opioid system, investigators using PET found that FM patients had decreased binding potentials at rest for the exogenously administered 𝜇-opioid receptor agonist carfentanil in several brain areas, including the ventral striatum, the anterior cingulate cortex, and the amygdala [92]. These areas are implicated in pain and its emotional modulation, and correspondingly, the binding potentials showed a negative relationship with the magnitude of affective pain scores relative to the sensory scores. Although results of this study do not tell us whether levels of endogenous opioids were increased or whether receptor availability was decreased, the findings support the notion that disturbances in the opioidergic system might be related to the increased pain sensitivity in fibromyalgia. For both dopamine and opioids, the ongoing widespread pain of FM could lead to a tonic activation within these systems and thus be a main factor in altering receptor availability and associated responsiveness to externally applied painful stimuli.

3.2. Neural Basis of Cognitive Symptoms

It is well known that cognitive capabilities such as attention and memory functions decline continuously across the adult lifespan [93], which, together with findings of accelerated age-related decline of brain gray matter observed in FM patients [84], suggests that there may be a relationship between gray matter reductions in FM and cognitive deficits in these patients. Two recent studies have linked FM to impaired emotional decision making [6263]. Anatomical imaging studies have reported that FM patients have decreased gray matter in the medial prefrontal and insular cortices [848589], areas implicated in emotional decision making [9499]. Together, these data suggest a possible association between gray matter loss and emotional decision making in FM. One study has directly examined the relationship between performance on working memory tasks and gray matter in FM patients and found that an individual’s performance was positively correlated with gray matter values in medial frontal and anterior cingulate cortices, thereby providing direct evidence for an association between altered working memory and gray matter morphology in fibromyalgia [51]. Both of these brain regions, together with lateral premotor cortex, lateral prefrontal cortex, frontal poles, and posterior parietal cortex, are areas known to be related to working memory processes [100105]. In terms of the neurochemical abnormalities in FM discussed above, dopamine plays an important role for cognitive functioning. Multiple lines of evidence demonstrate the importance of mesocortical and striatal dopaminergic pathways in memory tasks, perceptual speed, and response inhibition (see [106] for review). Thus, there is an overlap between tasks in which fibromyalgia patients perform poorly and tasks that are related to dopamine functioning, suggesting that a dysfunctional dopamine system could contribute to the cognitive symptoms of fibromyalgia.

3.3. Neural Basis of Sleep Disturbances

While many studies have used EEG and related methods to show various aspects of disordered sleep physiology in FM patients, little is known about the neurobiology underlying these disturbances. Several neurotransmitters have been proposed to influence CNS hypersensitivity associated with sleep alterations. For example, inhibition of the CNS serotonin synthesis has been linked to insomnia and increased pain sensitivity [107]. Accordingly, in FM there is evidence for low serum and cerebrospinal fluid serotonin levels [108109]. Injecting amounts of substance P into the CNS of rats has been shown to reduce sleep efficiency, increasing latency to onset to sleep and provoking awakenings from sleep [110], and there is evidence for elevated cerebrospinal fluid levels of substance P in FM patients [111,112].

3.4. What Do the Psychophysical, Cognitive, and Neuroimaging Studies Tell Us about the Neurobiology Underlying FM Symptoms?

The wealth of experimental evidence showing that FM patients are hypersensitive to painful stimuli, as well as unpleasant stimuli from other sensory modalities, in conjunction with functional brain imaging data showing increased stimulus-evoked activation throughout nociceptive pathways, shows that the defining symptom of FM—increased pain—is in fact real and not just a response bias of the patients. The finding that perception is increased in multiple modalities speaks against the hypothesis that FM pain is due to an upregulation of peripheral nociceptive processes. Further, psychophysical evidence that descending modulatory systems are altered in FM patients supports the opposing idea that FM symptoms are at least in part caused by alterations in CNS processing of the pain signal, including a dysregulation of pain modulatory systems. Nevertheless, the apparent dysregulation within these systems could be caused and/or perpetuated by a tonic activation related to the presence of ongoing widespread pain, so that the systems are saturated and cannot regulate further in response to external stimuli.

Since similar descending control systems, including attentional and emotional regulatory circuitry, affect multiple sensory modalities [113119], a dysfunction (or saturation) in these systems could lead to the hypersensitivity in multiple sensory modalities. FM patients show reduced habituation to nonpainful tactile stimuli and increased cortical response to intense auditory stimuli, both of which have been linked to deficient inhibition of incoming sensory stimuli [120121]. Also in support of the idea of a central dysregulation or saturation of pain modulation are changes in the opioid and dopamine neurotransmitter systems, both known to be involved in hedonic regulation [122].

Finally, the findings that FM patients not only perceive themselves to have altered memory and concentration (“fibrofog”), but also in fact perform poorly on multiple cognitive tests, even when depression is excluded as a contributing factor, suggest that there are alterations in brain function. The anatomical brain imaging studies that show reductions in gray matter in frontal regions important for cognitive function further indicate that this common symptom of FM is based on altered brain function. Together, the experimental evidence provides strong support for the idea that FM symptoms are related to dysfunctions in the central nervous system. The cause of these changes cannot be deduced from the available evidence, as it is correlational in nature. Did long-term ongoing pain cause the changes or did the changes cause the pain? Without a relevant animal model or long-term longitudinal studies, we cannot answer these questions. Nevertheless, we can at least say that fibromyalgia is real and that it is associated with multiple changes in the brain.


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Holding on to anger is like grasping a hot coal with the intent of throwing it at someone else; you are the one who gets burned.

Holding on to anger is like grasping a hot coal with the intent of throwing it at someone else; you are the one who gets burned.