Sometimes you don’t know if you should laugh or cry. This study starts off with a list of abnormal findings in fibromyalgia: there’s the central nervous system sensitization which involves increased activity in the brain’s pain processing regions, increased responsiveness in regions that that process ‘noxious stimuli’, and there’s an inability to become habituated to painful stimuli (the pain should diminish over time – not get worse!).
Despite all that is known about fibromyalgia many questions remain.
But then, the authors say, we really don’t have any idea what’s causing fibromyalgia! In fact, researchers know several of the things that have gone wrong in fibromyalgia, but they don’t know what’s causing them to go wrong. This study could bring us closer to what’s causing things to go wrong.
A recent study suggested that pain processing centers of the brain in young people protect themselves from a kind of pain signal ‘assault’ by ‘bulking up’ (increasing grey matter) and decoupling themselves from each other. Both these attempts get reversed in older patients leaving one more hypersensitive to pain.
This pain signal assault could be generated in three places in the body that I know of, and probably more: at the dorsal horn of the spinal cord (which filters signals to the brain), at the sensory ganglia, or in the sensory nerves. The study examined the sensory nerve network emanating from the skin to see if it was damaged and was sending unusual signals to the brain.
The Study
Researchers commonly stimulate the nervous system to see how it responds. In this study, laser-evoked potential (LEP) tests specifically targeted the small nerve fibers that carry the messages from the skin to the spinal cord . As the laser heated up the skin the researchers examined the electrical charge in the small nerve fibers to determine if they were functioning properly.
Researchers measured the nervous system response to laser induced pinpricks of pain in the skin
Because the small nerve fibers carry pain signals, they could be involved producing the neuropathic (nerve) pain present in fibromyalgia and chronic fatigue syndrome. Until recently, however, studies assessing small nerve fiber neuropathy in fibromyalgia and chronic pain disorders have been rare. Now some small studies suggest rates of small fiber neuropathy (SFN) in FM could be quite high.
This was a big study. Laser evoked potentials were done three times each in three different places in 199 patients as well as 109 age- and sex-matched controls. Skin biopsies to assess small fiber density were taken in three places each in 20 patients and 60 controls.
As a laser evoked pinprick and burning sensations at three tender points, the researchers measured the laser-evoked potentials produced and asked the participants to assess the amount of pain they experienced. The corresponding amplitude and habituation of the electrical response was measured.
The Findings
Nervous System Activity
The laser pinpricks evoked, not increased, but reduced electrical responses ( e.g. amplitude) from the sensory nerves in most FM patients relative to the controls. The reduced strength of the electrical signals resulting from stimulation by the laser indicated problems with the nerves were present.
People with migraine and FM tended, on the other hand, to have normal or increased response. This suggested that a very different subset was embedded in the larger fibromyalgia population.
Habituation
“The tendency not to habituate across consecutive sessions of painful stimulation seems to be a stable pattern in fibromyalgia, which is not influenced by psychological factors and is correlated to illness severity” Authors
The nervous system should quickly become habituated to and respond less vigorously to the laser pricks over time; indeed, the strength of the electrical signal (the evoked potential) dropped by almost 50% by the third pinprick in the healthy controls, but by only about 15% in the FM patients.
The pain inhibition didn’t fully kick in in many FM patient, and in some FM patients with migraine, the pain system got more responsive – not less
This suggested that FM patients’ nervous systems were inordinately provoked by the initial pain signals and had trouble turning them off. This kind of continuing arousal can be seen in a number of instances in FM and ME/CFS: in contracting muscles that never completely relax in FM, in a heart rate that does not calm down during rest, and in a sympathetic nervous system activation that doesn’t stop in both disorders.
One might also include the flu that never ends for many chronic fatigue syndrome patients. In both disorders an event (infection, trauma) triggers a response (sickness behavior and/or pain) that should get ameliorated over time, but the return response, which should swing the system back to homeostasis, doesn’t kick in.
In this case that the anti-nociceptive or anti-pain pathways descending from the brain were not kicking in to ameliorate the pain present in fibromyalgia.
Migraine and Fibromyalgia Subset
That was bad enough, but a subset of patients with FM and migraine (40% of the group) probably had the worst of it. By the third pinprick their nervous system response had not only not habituated, but had significantly increased indicating that their pain response system was revving up when it should have been revving down.
The researchers appeared to suggest that the central sensitization in migraine was so strong that it could produce fibromyalgia all by itself.
Migraine is becoming an ever more interesting aspect of both FM and ME/CFS. Rates of migraine appear to be quite high in both disorders, and it will no doubt be taken more into account in future studies. The authors suggested that the increased central sensitization in migraine this study showed was present could cause fibromyalgia to occur without any increase in pain signals from the body at all; i.e., the migraines are setting the foundation for FM to more easily occur.
This inability to reduce the central nervous system response to pain signals turned out to be important, as it was associated more than any other finding with reduced quality of life and increased pain levels at the FM tender points.
Small Fiber Neuropathy Found
“Our present opinion, which needs further confirmation by the enlargement of the skin biopsy data, is that idiopathic peripheral sensory nerve involvement may be part of FM syndrome.” Authors
Small nerve fiber neuropathy (reduced nerve fiber density) was present in 90% of the 21 patients tested. The authors noted that it was different from the kind of SFN than usually seen. This finding buttressed the finding of a recent study that also found reduced electrical signal responses in FM patients and which postulated that SFN was present.
The researchers suggested the same factors that reduced nerve density in the skin caused the central sensitization in the brain.
Recent studies suggest a strong genetic component is present in both fibromyalgia and chronic fatigue syndrome, and SFN may be heritable as well. A gene mutation causing hyperexcitability in the dorsal root ganglion neurons that process the pain signals is associated with severe neuropathic pain. (A mutation that reduces dorsal ganglia excitability is associated with indifference to pain.)
This study found considerable evidence of small fiber neuropathy, but the findings suggested that the lack of habituation by the central nervous system played more of a role in producing pain than the nerve fiber problems leading from the skin to the spinal cord. (That finding, however, was based on a small sample size.)
The authors suggested, however, that the small nerve fiber problems they found in the skin probably extended to the nerve fibers associated with the muscles and joints, and that ion channel dysregulation probably caused both the small fiber problems and the neuron problems associated with central sensitization. (A sodium channel polymorphism has been associated severe fibromyalgia. )
In short, they believe the same general problem is causing the small nerve fiber problems in the skin, muscles. and joints, as well as neuron problems in the brain and spinal cord.
I contracted fibromyalgia after being exposed to toxic chemicals in new carpeting in 1989. I have had no pain relief at all since then. I was told by the “experts” that my myelin sheath was destroyed along with my synovial membrane. Fyi.
Ouch. I believe some small nerve fibers are unmyelinated and some are myelinated.
I have a horrible time with new or even old carpeting…I don’t know how I was ever able to stand it; it is such a noxious substance to me now. It’s amazing the changes that can occur.
Thanks for your hard work in presenting these findings. Any chance you could point to the original study publication?
It’s known that migraineurs cannot “tune out” or “tone down” persistant stimuli, and their brains can actually turn up the volume on pain – makethislookawesome.blogspot.com/2011/11/what-is-migraine.html
People with ME/CFS have the same problem of being able to tune out persistent stimuli. Thanks for reference on turning up the volume. I was struck by Baraniuk’s studies showing a high incidence of migraine in ME/CFS. At least a decade ago, I think it was Chaudhuri and Behan who proposed migraine as a similar disorder to ME/CFS.
Cort, I love your posts and enjoy reading the advances into fibromyalgia which, in my case, was triggered thirteen years ago following traumatic spinal surgery and then two car accidents. Just one request, could you provide citations for the original research for those of us inclined to go back to the original work? Thanks and keep up the good work.
Sorry about that. I keep forgetting to do that. I put the citation in the blog and here it is as well. Please keep reminding me and I’ll get better at it.
J Neurol. 2013 Dec 24. [Epub ahead of print]
Update on laser-evoked potential findings in fibromyalgia patients in light of clinical and skin biopsy features.
de Tommaso M, Nolano M, Iannone F, Vecchio E, Ricci K, Lorenzo M, Delussi M, Girolamo F, Lavolpe V, Provitera V, Stancanelli A, Lapadula G, Livrea P.
Fascinating findings Cort but also much more complexity in there with these various ‘sub-groups’.
In the context of your previous article, I wonder how the results would have panned out with age as an additional variable?
Yes, three subgroups – regular FM, FM with migraine and another smaller one I didn’t mention; FM patients with neurological problems in their feet, I think it was. Getting more complicated all the time, but if these diseases are all related I think this is what we would see. All the groups had small fiber neuropathy (noting that the sample size for that was small) but there were differences in the laser evoked potential tests.
No point into going into all of my health issues, which are long & complex, but being a fibromyalgia sufferer & knowing the daily devastation it can have, not only on myself by form of pain, but also my family (wife & young children). Being unable to work as near housebound with severe mobility issues, it’s just great to know that so much research such as this, is going ahead!
With the amount of such research, there remains what surely must be high hopes for maybe not a cure, though that would be amazing, but hopefully at the least this kind of work should pave the way for far better pain medications to be manufactured, which would hopefully give a better quality of life for many millions of people.
Wishing the best for all sufferers of this & similar conditions!
I would think so, Jason…Every bit of research that finds something should help, I would think.
I was diagnosed with CFS in 1994 and with peripheral neuropathy, from an “unknown cause”, around 2000. When I had new nerve conduction studies and a nerve biopsy a few years ago, the biopsy showed neuropathy in the small fibre (ganglia) nerves. At my first visit to Dr. Chia, he said my neuropathy was most likely caused by he enteroviruses that, he believes, are the cause of my ME/CFS. It all made sense to me then. One cause…several areas of damage leading to many symptoms.
I also used to be plagued with migraine pain. When my internist helped me get control of my allergies several years ago, the migraine pain was relieved. I still get migraine episodes of aura but, fortunately, without the intense pain.
It too am thankful for all the research that provides solid evidence of the physiological damage of this disease. I am hoping (and praying!) Dr. Chia’s research regarding the cause will get the attention it deserves at the upcoming IACFS meeting in March.
Thanks for another great article, Cort!
Thanks Christine – interesting about the connection between migraine and allergies! :). Dr. Chia is giving not one but two talks at the conference. It should be good!
Will there be a way to view the talks at the conference?
I think a video will be made that you view later.
I have been ill with CFS/FM for 27 years and seem to be getting progressively worse. I attribute this to getting poor medical advice, continuing to work (PT) because I was too stubborn to give up my career, the stresses of parenting and life in general…and basically wanting to function as a “normal” person. Whenever I read about CFS being related to trauma I pay close attention. I believe too many traumatic events (physical and emotional) contributed to my illness onset. My nervous system is always hypervigilant and I can’t help but wonder if this has caused physical damage to some of my body’s nerves. I have all the symptoms of small fiber neuropathy and my neurologist has agreed to order the kit to do skin biopsy testing. I have to wait 3 weeks to get tested and then another 3 weeks to get my results. I live in Denver and the specimens have to be shipped to LA. I would be happy to report my test results if anyone is interested.
Thanks Tanja, please let us know how it goes! Good luck with everything.
At the risk of sounding like a nut, I’d like to register a strong objection to the term, “sickness behavior.”
I know that psychologists may find it useful to define a person feeling and acting like they have the flu as “sickness behavior.” However, that description seems to me to imply we are somehow behaving in a volitional way that we could change if we wanted to. Why not just “sickness”? Why tack on “behavior”?
We are ill. To call the manifestation of being ill “sickness behavior” is to gloss over and lump together much that needs to be looked at, taken seriously and teased apart.
It is a weird term and I can understand your concern, but it didn’t come from psychology; it was coined to describe the constellation of symptoms associated with colds that are produced in order to keep a person from coming into contact with others and to conserve energy. Researchers believe it is an adaptive response by the body to keep infections in check and from spreading throughout the community – thus the behavior part.
Thanks, Cort. I do know what you’re saying is true. And I still don’t like it. 🙂 You wouldn’t hear scientists talking about “cancer behavior” or “AIDs behavior,” right?
Anyhow, just as well they didn’t ask my opinion. Every now and then I feel the need to rear back on my hind legs and object. I’ve objected. Thank you for providing the forum to do it in!
Hi, Cort,
This is a very interesting study, particularly about the subsets. However, I seem to cover all three groups: In my vision I have auras as well as a tiny black hole in my vision, which grows to take over all my sight. I also have small fibre neuropathy in feet and hands, as well as swollen feet and calves when I get hot.
For the auras and black holes, I’ve learnt not to look up at the sky or spend long outside if the light is very contrasty, and try to avoid looking at bright lights—though that can be hard to do, (one glance and that’s it). If I get caught, an aura starts immediately and I have to get back inside and spend some time just sitting quietly looking down at the floor in a dark room.
For the pain of the small fibre neuropathy in feet and hands, I now take Lyrica and Cymbalta, which reduce it a bit and help me sleep really well. For the swelling and pain when hot I take a cold pack with me when I go out to put on my feet.
It would be great if research could find a way to combat all that!
I posted a comment a few weeks ago about being scheduled for a small fiber nerve biopsy test at my neurologist’s office. Well, I went back to the neurologist’s office yesterday for the biopsy, filled out the consent forms, and then met with the doctor. He then decided that he wouldn’t do the biopsy after all. No great reason all of a sudden. His comment was, “well, even if you have it, there isn’t any treatment, so why do the biopsy?” I practically begged him for the test just so I would know if I have SFN or not. If not, then I would likely pursue another cause of the widespread nerve pain. He told me I should go to the Mayo Clinic and I told him (again) that they don’t treat CFS. This felt like another brush-off by a physician who doesn’t want to deal with CFS. I wonder if we shouldn’t even mention that we have CFS when we go to physicians because many of them don’t want to deal with us.
I notice I have many different types and degrees of pain. The higher my stress level and physical activity level the greater the pain…..and it’s a different kind of pain than the other types I have daily (aching pain and pins and needles pain)…..this is more like being bathed in a caustic acid from head to toe. Does anyone know if this type of pain could be from elevated lactic acid levels in our systems? Is there scientific evidence of this and if so, how do we control pain from it? Neurontin doesn’t even help. My bladder is on fire most of the time. Don’t want to go back on narcotics.
I have another question which is unrelated. and maybe should be kept for a different discussion, but it seems like more CFS/FM suffers are introverts, creative intuitives, very successful, and highly sensitive to their environments (ex. notice things no one else does, have highly aroused nervous systems even from childhood). All of these “traits” predispose us to more health problems. Is this being discussed anywhere?
I think you should send this blog – http://www.cortjohnson.org/blog/2013/08/20/from-chronic-fatigue-syndrome-to-fibromyalgia-to-pots-to-success-one-womans-journey-through-the-medical-profession/
to him. It tells the story of someone who was told the same thing only to find something that did treat her SFN and improve her health greatly.
Good luck!
Cort,
Thanks for sending the blog about Lauren Stiles. If I thought there was a remote chance the doctor would read it, I would send it to him. Unfortunately, I think he has written me off as a “nut case.” He told me I need a team of specialists, including a psychiatrist. Of course I got offended when he mentioned psychiatrist. He might have been recommending a psychiatrist because I told him about a recent bad experience with trazodone (for sleep). I either got Serotonin Syndrome (excess serotonin) or an usual reaction to the medication (it can happened – get overstimulated). It’s supposed to be sedating, but I got overstimulated instead and felt like I was on an LSD trip. Rather than discuss this unusual reaction the doctor wrote me off as a crazy person – end of discussion.
I don’t know if others have had unsual reactions to SSRIs or SNRIs. This was my first really bad reaction to an SSRI. Some of my notes from a Dr. Cheney lecture mentioned that CFS patients should avoid these meds becaue they upregulate things we don’t want to upregulate. Guess that is what happened to me.
Thanks for your great work, Cort. REALLY appreciate all that you do!!!
I live in Louisiana and was wondering if you are aware of the closest place doing this type of research. I spoke to a Neurologist today about doing the skin biopsies and although he definitely agrees it makes 100% sense, he says the pathologist that he would send the biopsies to wouldn’t know what to look for, therefore I should be tested in an area where research is being done, and they know what to look for. After that, he would be willing to treat me, based on what was found, and the meds that were suggested for me to take.
Interesting. Mass General is looking for samples. We’re trying to get something together with that…Dysautonomia International should have a list of testing labs. Your doctor should be able to get a kit from the lab – send it off to them and they will provide the results.
erythromelalgia from serotonin syndrome; a possible relationship?