The similarities are striking: the symptoms, the shoddy research funding, the poor treatment from doctors, the gender imbalance and the stigma both still face. Both diseases still really exist on the fringes of medicine and medical research.
The gap between ME/CFS and FM in terms of research funding, activity and energy is widening
Yet one disease is moving forward rapidly and the other is not – and it’s probably not the one you think.
That disease has a great name.. That disease has three FDA drugs approved for it, a specialty it fits in (however awkwardly) and a home at the National Institutes of Health (NIH). The other disease has a putrid name, has no FDA drugs approved (and none in the pipeline), no specialty associated with it, no home at the NIH, and its community has a (mostly undeserved) reputation for being hard to deal with.
In almost every way, FM appears to have a leg up. With its much higher prevalence, it clearly has more financial and social resources potentially available to it. It has the attention of the drug companies, which have produced several phase II or III drug trials over the past couple of years. Plus, it’s embedded within a field (pain) that’s getting a lot more attention.
When it comes to numbers, there’s no contest: fibromyalgia affects ten million people in the U.S. and has a massive Facebook presence, while ME/CFS affects about a million and isn’t close on Facebook.
Facebook Likes
Fibromyalgia
- Fibromyalgia by ProHealth – 455K
- FM Awareness – 255K
- Fibromyalgia – New Life Outlook – 231K
- Living with FM – 158K
- Fibromyalgia Inspiration – 45K.
Compare that to the one million people in the U.S. with chronic fatigue syndrome (ME/CFS).
Facebook Likes
Chronic Fatigue Syndrome (ME/CFS)
- Chronic Fatigue Syndrome and ME by ProHealth – 118K
- Open Medicine Foundation – 37K
- Solve ME/CFS – 34K
- ME Action – 16K
- Chronic Fatigue Syndrome/Fibromyalgia is Treatable – 8K.
Growing Divide
Yet the divide between the two diseases is growing – and not on the FM side. There’s no question that ME/CFS, formerly known as the “yuppie” disease, with its rep for having a difficult-to-deal-with community, is pulling away. It’s making strides at the federal level, in the research arena, in advocacy – even in the media. While ME/CFS is far behind the 8-ball with regards to treatment, there’s an energy, and commitment to improve its lot, that doesn’t seem to be present in FM.
Plus, while ME/CFS research is trending in the right direction – towards more pathophysiology – FM research appears to be going in the opposite direction, towards a more behavioral/psychological interpretation of the disease.
Research
In an article titled “Fibromyalgia Researchers, It’s Time to Stop Watching the Flowers Grow!”, Donna Gregory Burch recently reacted with understandable dismay to a study assessing the effects of a “flower design” course on the pain in fibromyalgia. Mind/body interventions can be helpful with chronic pain, but when researchers can get funding for a study on the effects of flowering arranging on FM something has gone very wrong, indeed. Donna ended:
“The truth is that too many FM studies are similar and there’s too little an emphasis on understanding the biological causes of the disease. The increasing emphasis on mind/body elements in FM is surprising given the increasing interest in physiologically understanding chronic pain.”
She is so right. The HEAL Initiative is pouring hundreds of millions of dollars into understanding and developing new treatment options for chronic pain, yet there’s no evidence any of its funding is going to fibromyalgia – which has been described as the quintessential pain disorder.
The recent Quest newsletter produced by the National ME/FM Action Network in Canada noted that a new emphasis on pain research there has largely bypassed FM as well. Since, of all the pain diseases, the pain found in FM is not associated with an injury to a specific tissue, the disease provides a superb opportunity to observe pain sensitization in its purest form; yet it doesn’t appear to be happening.
NIH Funding
NIH-projected funding for fibromyalgia and ME/CFS in 2020 is $12 and $13 million. That works out to just over $1 per FM patient per year and $13 per ME/CFS patient per year. Four years ago, ME/CFS was receiving $8 million and FM $11 million. Since then, ME/CFS funding has grown 50% while FM funding has grown less than 10%.
Research isn’t the only area FM has lost ground. A look at activities on every level (research, federal, advocacy, treatment) reveals a large disparity between ME/CFS and FM-initiated efforts.
ME/CFS
Federal Activities
It hasn’t been easy and for many years one wondered if the work to get the feds involved made any difference at all, but things have started to change for ME/CFS at the federal level. Structural components (particularly CFSAC) were laid down early in the disease which ended up making a major difference (via the production of the IOM/P2P reports). Over time, the ME/CFS community has produced:
- Three NIH-funded ME/CFS Research Centers
- One five-year NIH intramural study
- Five year funding for Canadian ME/CFS research network that will collaborate with NIH-funded U.S. Center
- A year long project to have the NIH create a strategic plan
- Long term CDC effort on ME/CFS
- Institute of Medicine Report (now National Academies of Sciences)
- Pathways to Prevention Report
- Common Data Elements project to standardize research protocols in ME/CFS
- Federal Advisory Committee For ME/CFS (CFSAC for @15 years)
- Special Emphasis Grant Panel for ME/CFS grant applications.
Private/Public/Non-Profit Research Efforts
Small but vital independent research efforts have at times made a major difference. The focus on exercise may not have existed without Solve ME’s backing of Workwell Foundation. Similarly, Jarred Younger’s big NIH grants were seeded by pilot studies. Over the past year, the Open Medicine Foundation has opened two new ME/CFS research centers at Harvard and in Sweden.
- The Open Medicine Foundation (Stanford/Harvard/Uppsala)
- Solve ME Initiative
- Institute of Neuroimmune Medicine (Nancy Klimas)
- Bateman Horne Center
- Invest in ME
- MERUK
- Euromene – European Consortium focused on ME/CFS.
Treatment and Education Efforts
- Clinicians Consortium (Bateman Horne Center)
- CDC Website renovation
- Workwell Medbridge Project
- Pandora’s Continuing Medical Education (CME) Course
- Stanford commitment to improved ME/CFS clinic integrated with Ron Davis’s research
- New York State ME/CFS Declaration.
Infrastructure
- Biobanks – Solve ME/UK (NIH-funded)/ Canada – coming
- International Patient registry – coming soon (Solve ME)
- Stanford (and soon Harvard) Open Data Base for Researchers
- Fatigue Journal (IACFS/ME).
Conferences
- NIH-Sponsored International Conference (2019)
- IACFS/ME Biannual International Research Conferences
- Invest in ME Annual International Research Conferences
- Open Medicine Foundation-sponsored Stanford Working Group
- Solve ME Research Colloquium (dating back decades)
- Invest in ME Research Colloquium.
Advocacy
- Full-time professional patient advocate for ME/CFS (Solve ME)
- ME Action – devoted to ME Advocacy
- Part-time advocate (David Tuller) supported by ME/CFS Community
- Continuing broad efforts to overturn PACE trial
- Connection with NOW and other organizations.
Media
- Unrest / Forgotten Plague documentaries
- Jen Brea TED Talk
- ME/CFS Alert – Llewellyn King ongoing video interviews.
Fibromyalgia
Not being as immersed in the FM field I may have missed some effort.
Research Organizations
- I was unable to find any FM organizations currently funding research.
Conferences
- International Congress on Controversies in Fibromyalgia – a several day conference
- Fibromyalgia Awareness Conference (the 19th!) – 1/2 day conference.
Federal Efforts
- I was unable to find any federal efforts specifically focused on fibromyalgia.
Media
- A film called Invisible was reportedly under production.
Advocacy
- Fibromyalgia Advocacy Day hosted by the International Support Fibromyalgia Network … is today and tomorrow – and advocates have flown into DC to ask for more FM-specific funding
- Other advocacy efforts may be occurring but I was unable to find them.
Current Research
Rather alarmingly, a look at recent FM research citations suggests, as Donna proposed, that the trend overall in the FM research field is towards more and more mind/body research and less pathophysiology.
The last 20 fibromyalgia and ME/CFS research citations in PubMed (where each disease was mentioned in the title) reveal an astonishing split. Fibromyalgia research was dominated by mind/body/psychological efforts while efforts to understand the pathophysiology were uppermost in ME/CFS.
PUBMED CITATIONS
Fibromyalgia
Mind/Body/Exercise
- Tai Chi
- Heart rate variability biofeedback
- Social support, anxiety, depression and severity of pain
- Goal preferences, affect, activity patterns
- Power of flower arranging course
- Walking as exercise
- FM and obesity
- Obesity, smoking and socioeconomic status
- Sexual desire
- Positive affect intervention
- Physical factors – quality of life
- Mindfulness and acceptance-based interventions for FM
- Flexibility exercise training.
Epidemiological
- Disease impact
- Diagnostic criteria.
Biological
- Neuropathic pain syndrome
- Pro-inflammatory cytokines
- Brain network hub stimulation
- Immune factor effect.
Non-Mind/Body Treatment
- Duloxetine.
Chronic Fatigue Syndrome
Mind/body
- Recovering – Intra-active process
- Management of ME/CFS
- Relationship satisfaction, communication
- Factors associated with work status.
Non-Mind/Body Treatment
- Novel Therapeutic Interventions.
Epidemiological and Clinical
- Promis Fatigue Short Form
- Symptom Assessment
- Documenting Disability in ME/CFS
- Short Form DePaul Questionnaire.
Research
- Antibodies to Herpesviruses
- Inflammatory Proteins
- Cytokine Review
- ME/CFS Comprehensive Review
- Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test
- Nosology of Causation
- IDO Metabolic Trap Hypothesis
- Machine Learning Diagnosis
- Pathological Mechanisms
- Biological Basis of ME/CFS
- Biomarker Test.
Discussion
Both diseases – still stuck at the bottom of the NIH funding ladder – are a work in progress. Movement in one should help the other
It’s true that ME/CFS has a long, long way to go – in some areas such as treatment, a much longer way to go than FM. The number of NIH grant applications for ME/CFS research, for instance, remain abysmally low and ME/CFS- knowledgeable doctors are exceedingly rare. FM does have one more big thing going for it – it has the numbers. With approximately ten times as many people affected and better name recognition than ME/CFS, the FM community has the potential to far outstrip the ME/CFS community in garnering federal and other resources.
With its active federal presence, its research foundations, its federally funded research centers, its strategic work on the federal level, the focus on pathophysiology, and its active media presence, there’s a sense that ME/CFS is moving forward.
One question is why the ME/CFS field seems to have captured so much more energy and unleashed so much more creativity.
The early creation of an organization of research professional (IACFS/ME), the regular international conferences, a professional advocacy and research organization (Solve ME), all helped set a tone. The publication of Osler’s Web surely galvanized many. While FM organizations appear to have largely given up on funding research, Solve ME has been able to maintain a research focus for 30 years.
The field was later boosted by Jen Brea’s efforts to create ME Action, her film (Unrest), Solve ME’s return to advocacy, and the entry of Ron Davis in conjunction with the emergence of the Open Medicine Foundation. Davis’s effectiveness as an effective researcher/spokesperson for ME/CFS has helped bring many dollars into the field including a one-time $5 million dollar donation. The harsh environment in the UK triggered aggressive and organized advocacy and research efforts by Invest in ME, MERUK and others.
FM advocates can look to some of the thing that have worked for ME/CFS.
- Efforts to work within the NIH to create federally funded reports that highlighted the needs in ME/CFS
- Private non-profits such as Solve ME, which made research a priority early on, and funded many pilot efforts which took seed in ME/CFS
- An early focus on advocacy – although it appeared for many years to have little effect – has reaped dividends in the last five years
- For all its weaknesses, the federal committee on ME/CFS (CFSAC) did provide a place for experts, advocates and NIH officials to establish relationships and work together.
- Bold actions have paid off: Jen Brea had never created a film (Unrest) before or an advocacy organization (MEAction). Linda Tanenbaum had never lead a research foundation (OMF) – both have been very successful.
Fibromyalgia, on the other hand, has three FDA-approved drugs and the interest of pharmaceutical companies – two things the ME/CFS community is missing.
FM advocates can take heart in the immense possibilities present before them. With about ten million affected, the FM community has the numbers to move the NIH and get more and better research, get better doctor training and better treatments.
It can view the ME/CFS community’s progress with hope. Who, after all, would have expected little ME/CFS, with its weird name and dodgy reputation, to have the ear of the NIH Director or to rebound from its worst funding period ever with three research centers and a large intramural study? If ME/CFS can do that, FM can do far more.
It would be a good thing if it did. Both diseases need each other to thrive.
https://www.google.com/search?q=the+gadolinium+hypothesis+for+fibromyalgia&oq=the+ga&aqs=chrome.0.69i59j0l5.2157j1j7&sourceid=chrome&ie=UTF-8
I have Gadolinium induced fibromyalgia. MRIdye.com.
The problem is that the medical community is a contributor to the problem.
júst when I’m practically begging my GP for another MRI but with contrast fluid this time……
Just diagnosed . I have had multiple MRI’s. Is there a journal article proving this? Please share
Years ago, I saw a Rheumatologist for my ME and now, with no ME specialists in Nashville, I again see a Rheumatologist. She believes Fibro and ME are essentially the same disease on a continuum with Fibro having more pain and ME having more fatigue. This is based on literature in the Rheumatology field. Speaking clinically now, I wonder how we can use their belief that it is all one disease into creating more clinicians to treat those with ME and others like me with both?
Dr Batemen feels the same way and this points out another reason why people with ME/CFS should want the FM field to grow and thrive. Whether you’re diagnosed with one or the other disease could simply depend on the doctor you saw!
I recently saw Rheumatology at Indiana University. She labeled me with FM based on the 2014 diagnostic questionnaire. Based on that criteria, EVERYONE with CFS/ME has FM. She wouldn’t even look at the diagnostic criteria to CFS/ME or other info I printed from the CDC. Her response “I don’t need that. The treatment is the same for both.” It isn’t. Not by a long shot. She threw scripts for antidepressants at me and told me to do graded exercise therapy. I told her I couldn’t. She told me to try. Since she didn’t want to look at the data I brought her, I read the part about GET causing permanent damage to CFS/ME patients. She rolled her eyes at me and told me to try anyway. Physicians believing CFS/ME & FM are the same disease is not a good thing in my book. Especially when a doctor in Rheumatology won’t see you if you’ve been diagnosed with FM. I could only see the nurse practitioner, who obvious believed I was a nut-job waste of her time even though I traveled 150 miles for that appointment.
Yes, there’s quite a bit of evidence suggesting that people with FM can do more exercise than people with ME/CFS. There’s also evidence that they are exercise limited as well.
Your experience shows though how limited the treatment options are for FM as well.
I agree that Fibromyalgia and ME/CFS are very much alike. I am about to turn 65 and have had Fibro since I was a little girl (as did my Mom). I found exercising helped me and got hooked to it in my 20’s and 30’s. I know just when I added ME/CFS to my life, 22 years ago, the summer that I caught Mono while taking care of my daughter who had it. I felt like somebody turned my light switch off in my body and I felt like I was half dead. I never knew what PEM/PENE was before this, but I was feeling it from that point on. I’ve been housebound and recliner/bedbound for the past 5 years. My rheumy takes care of my Fibro and is learning about ME/CFS for me as his one and only ME/CFS patient. I see him when I can, as it takes weeks/months to get over each visit.
She is spot on as well as you!?Very possible to have both to as well consideration to what has happen via accidents or viral that a person(s) has been subjected to in thier past! I can’t do the dye as well for MRI’s..not sure if dr.s have take note and how many of us can’t (data) Thanks Cort for the update on the happenings! ??
WoW that’s wonderful news, I believe I have both, but in Australia research is so limited, I was diagnosed in 1999 after years of suffering from a teenager, l am now 61.
I’m sooo glad I read your message, it gives us all hope that one day MEDICAL’s will wake up Kind Regards Louise ?♾?
I feel they are essentially the same. Suffered since being driven in to a car crash nearly 6 years ago. CFS/FM/BRAIN Fog and ME.
Just stagger on by myself… England
Esther, I agree with your doctor. I was diagnosed with fibromyalgia 4 years ago, though my most debilitating symptom that I’ve struggled with for decades has been increasing fatigue. I don’t know why I was never diagnosed with CFS, other than maybe my doctors didn’t believe it exists. Maybe an approach that pools resources and studies both fibromyalgia and CFS/ME would result in more answers for both diagnoses.
I was diagnosed with both Fibro and CFS as well as autoimmune fatigue, at Mayo Clinic (I also have autoimmune disease).
Mayo Clinic believes both Fibro and CFS are Central Nervous disorders.
For Fibromyalgia, there is now a blood test with high accuracy – see fmtest.com by EpicGenetics. EpicGenetics is also collecting blood samples to search for a DNA indicator. You may wish to add something to that effect to your article. Yes, I agree, more funding and structure needed for both illnesses!
Why is it necessary to set up a competitive climate between ME/CFS and FM? The framing of this article leans confusingly toward conflictual comparison. Surely there’s a more constructive framing that provides the same information and thoughtful points, without a sensationalized framing of who’s the surprise candidate in a difficult struggle for recognition, support, funding, and productive research.
ME/CFS and FM need each other to transcend sectarian striving.
You disagree with the framing – that’s OK, I understand that. I’m sorry that the way the article was framed got in the way of the main points. The article was framed the way it was to get attention.
The first step to solving a problem, though, is recognizing that one exists and that’s what this blog was about. I don’t know that people with FM know what’s possible; i.e. what’s happened with ME/CF or what the state of the research in FM is.
You mentioned “the difficult struggle for recognition, support, funding, and productive research.”Yes it is a difficult struggle – but I don’t see that struggle for “recognition, support, funding and productive research” coming from the FM community. That’s hard to hear I know, and I don’t know why that is, and I certainly don’t think it has to be that way. While the blog may have ineptly framed the issue or framed it in a way that offends – I hope it will galvanize efforts to increase funding, produce better research and ultimately better treatments.
For several years, for example, it’s been clear that research in FM has become more and more focused on a mind/body/psychological approach.
A better question would be given that this seems to be happening – how to galvanize the community to stop it from happening and to advance research. My hope was that showing what the ME/CFS community has done will provide ideas and hope for the FM community. Sometimes it just takes a few individuals coming together.
I appreciate how the author compares and contrasts in order to discuss in very practical terms what each community can learn from the other’s successes/advantages. The closing line says it all: “Both diseases need each other to thrive.”
I couldn’t agree more! I have more FMS and ME/CFS. Which side am I supposed to be on. We should be glad either is getting more attention.
Hello Cort,
I love your expertise and dedication!
this wesite , the info and support is amazing,
Am grateful – wendy
I’m an old codger and amazed to see that social media “likes” count for ANYTHING with ANYONE. Maybe I’ll just toddle off into the sunset with my corded phone and library card.
🙂
When I was a kid I made a pact with my friends that whoever got a girlfriend first would see to communicating to others girls that the rest of us guys were in fact cool.
Fibrofriends, don’t forget us fatigueds when you have your breakthrough!
(Have their been any effective efforts for ME/CFS, FM, Lyme, Gulf War Illness and others to lobby for resources as one body or lobby on each other’s behalf? Surely we’re stronger together.)
Virtually none. It sure seems to make sense but it hasn’t happened. These diseases share so much that you’d think they would at least be studied together but they rarely are.
That’s really unfortunate as breakthroughs in one disease take some time to bleed into the other. It is happening. Small nerve fiber issues have been studied in FM for about 5 years but it’s only recently that they’ve been studied in ME/CFS (and guess what – they’re present :)).
That never would have happened for ME/CFS if fibromyalgia researchers hadn’t taken up SFN.
FM: ~10 million
CFS: ~2 million
Post-treatment lyme: ~2 million
Gulf-war: ~half million
There may be some overlap, but likely even more missed diagnoses.
15MM Americans is not an insignificant voting block.
If you had to coin a term for this group of underserved diseases that would be used for a question in an upcoming presidential debate, what would it be?
Thought 1: Branding 101 says it shouldn’t be “underserved diseases”… or we’re coining the whole concept around the exact thing we _don’t_ want to be.
Thought 2: In some fields today the idea of being interdisciplinary is a hot topic and people are flocking to these new hybrid roles (e.g. “Growth hacking” or “Design thinking” in the business world). How do we rebrand chronic diseases that span traditional silos in the medical world to emphasize how solving them is the next great challenge in medicine?
@Winston, to your question about “branding” all of these diseases?
I like OMF’s term: “neuroimmune” diseases. It has a nice ring in that they contrast with “autoimmune” and entail a similarly BROAD concept that a ton of disparate things can go wrong (tons of symptoms) with fairly similar causes (eg, Crohn’s and RA and MS are very different, but all in theory entail deranged autoimmunity; “neuroimmune” illnesses may look like Lyme or CFS or FM or GWS…but all of them have to do with how the immune system has basically taken “errant” tips from the nervous/endocrine systems to kind of “give up” or shut down. It can be allowing spirochete bacteria or common EBV/herpesviruses to wreak havoc). I’m just unclear how this name might “cover” for instance the small nerve fiber issues, or the metabolomic derangements we see in CFS; is that the “immune system” per se? (Do small nerve fiber issues entail abnormalities with microglia?)
ANyway… one suggestion to “brand” this complex cluster of illnesses so as to UNIFY us folks!! And jam it through folks’ thick skulls that there ARE biological causes underlying our suffering.
….and is the deranged pain signalling in FM…all the different pathophysiologies proposes…to what extent is that too an “immune”/”neuroimmune” issue? I don’t usually stereotype FM as an “immune problem the way I do for CFS (my (non)diagnosis lol) but if cytokines and “immune factor” is involved I’d say it is definitely an immune issue! #semantics! #branding!
Regardless, I agree this element is important to helping laypeople AND ignorant docs get a grip. And there is SOLID evidence to believe they’re all related!! Let’s find a name!! A “brand!”
Even if somehow we’re proven wrong eventually that these diseases are all sister illnesses, I’d rather be proven “wrong” by GETTING all that research and clarity–and once we understand shit better, have the AMA/whoever actually do their freaking jobs and devise not only better classification schema but better TREATMENTS–than continue for MORE years with the millions of us in pain and debilitated and floundering in the no-woman’s land of “hmm is it real? you just feel like you’ve been hit by a bus cuz you have a anxiety/laziness/depression/a cold….”
Dr James Baraniuk at Georgetown Univ Hosp has published many reports on Gulf War Syn funded by DoD. He’s done work on FM/ME/CF. I know because I have participated in his studies since I have both. I believe he has seen similarities with Gulf War Syn. Thank you for your blog.
Yes – he’s moved around quite a bit – thankfully – and been a great supporter of ME/CFS.
Just out of curiosity – have oxalates been looked into very much as one potential cause of the pain of fibromyalgia? I don’t see them on the list above, but I’ve seen fibromyalgia mentioned in literature on oxalates.
An Organic Acids Test (OAT) would indicate if this is a problem for some.
https://youtu.be/ZOTMJYbDQok
This is what has made me so angry in the past few years within the medical and social field surrounding fibromyalgia. ME is making its way into one of the most revolutionary social organisations in the realm of medicine, pushing for awareness and biomedical research, but everything has stopped concerning fibromyalgia. In the end, what do we really know? That fibromyalgia is caused by something within the CNS. Why are we not pushing for more? Fibromyalgia sits within rheumatology, without having any correlation to rheumatological conditions. Research is focusing on psychological issues, rather than biological. 2% of the worldwide population is thought to be affected by fibro. So why are we not doing more? The ME community is doing everything to bring forward research. Why are we not?
ME/CFS got off to a great start early on. We lucked out with the publication of Osler’s Web. We were lucky to have a very professional organization (CAA) which was involved politically and in the research from the beginning. We lucked out big time with Jen Brea! We lucked out when a major, major researcher – Ron Davis – who has been very outgoing publically – got involved. Sometimes you just get lucky.
When I looked at migraine several years I couldn’t find any evidence of patient advocacy – and migraine is much bigger than FM. I don’t know why advocacy gets going in one disease vs another. Migraine, by the way, gets abysmal funding at the NIH. It’s another pain disorder that affects more women than men which which gets terrible funding.
ME/CFS went through a long downward spiral but things have turned around. We have allies in the NIH and in the federal govt. Those NIH funded reports made a big difference. Somehow it feels like its starting to come together – and it can for FM as well.
I don’t think the FM community is happy with their treatment options, I don’t think they are happy with their doctors, (I don’t think FM should be in NIMDS either – it should be in NINDS). I don’t think they’d be happy to know that researchers are getting funding for the effects of flower arranging classes.
I would be interested in knowing how many Fibro/ME patients ALSO have another chronic illness? My chronic illnesses are not related-and so two different types of physicians must be included. However, Rheumatologists and spine neurologists and spine surgeons know nothing about the illness they’re not treating. They don’t want to learn. And they all mark me as a difficult patient because each doctor wants me to do (or not do) the opposite of each other! I also wonder how many M.E. patients have immediate family members with severe chronic autoimmune diseases? I have 4 daughters, each severely sick with Juv. Rheumatoid Arthritis, severe Chrones disease, Hydretinitis Supervativa, Ulcerative Colitis. I wonder if this might be more common than most researchers think?
calcium citrate and magnesium citrate with each meal, as per Great Plains Lab (OAT) consult
have had some some positive impact on one type of pain- Does not help burning but helps pain. Their consultant said to increase the dosage if
I didn’t improve. I tested high in oxylates.
I’d like to see a documentary on the utterly appalling history of ME/CFS, from eye rolling doctors and nurses to those in the psychological and psychiatric fields who conspired to make the disease appear to be a mental illness solely for greed. They received £5 million pounds for the fake PACE trail. I hear those involved even own a pacing and CBT clinic. Then there’s the NIH who epically failed even when data was repeatedly shown to them. And the immense ‘prolonged’ suffering of patients because of all the politics.
The documentary would have its heroine’s and hero’s too, the Davis’s and Bateman’s, Bree, etc. It should especially show the convincing biological discoveries and abnormalities in ME/CFS patients. Interviews with leading researchers. And their views on the PACE trial and how badly it effected the ability to attract new biological researchers.
It really was fraud and lies on a massive scale
It would make gripping television or film. As anything that makes people angry at the wrongfulness of it all will gain numbers in support and advocacy.
My brother is a high profile film editor in NZ who has worked with Peter Jackson, so if someone with good cinematic skills films it on a quality gear I’m pretty sure he would either edit it for me because I have severe ME. Or if he can’t do it then he’ll still know or guide someone to do it.
email me if anyone has interest and the skills in documentary making
vespa.bw@gmail.com
Terrific article! So clear. I had no idea about the issues you described for ME/CFS and FMS. As a person with “mostly” FMS, and some ME/CFS, I feel discouraged that the two fields don’t interconnect with each other. One could throw in MCS, too.
It makes a bit of sense experientially– I’ve found FM-like symptoms more amenable to mind-body work than the fatigue side — though I agree the research trend is a bummer. I have nothing against mind-body research but this is obviously a genetic-biological disease.
There is the Epic Genetics/Mass General BCG vaccine study. It was suppose to start earlier this year but my understanding is that Epic Genetics delayed it because they couldn’t find enough male subjects and they wan to incorporate a genetic finding from Illinois-Chicago researchers into the study.
There’s also Jarred Younger, bless his heart, and a couple labs at Ohio State (the one that claims to have a blood test and the one that does the HHV-6 research). But otherwise I really don’t know of much.
Dear Cort, I want to thank you for all the work you do to keep us up to date on any possible advancements in this terribly perplexing, depressing field. It is such a help to read what others with this disease say, especially because every trip to my doctor is an experience in total frustration. There is no curiosity nor willingness whatsoever to even look at what could be causing all this pain and total lack of energy. No wonder so many of us have become our own “experts” on the subject, because we have certainly not been respected or taken seriously in the doctors’ offices. Thank you again for making this a national issue that must get serious attention from medical authorities. I agree that the millions of us with these mystery disorders need to unite. Nothing was done about AIDS until the whole community got activated. But it is really hard to be “active” when one is so existentially exhausted. Best wishes to all.
So true. It’s hard to be an activist when just brushing one’s teeth brings on severe P.E.M.!
Let’s not forget Ehlers-Danlos Syndrome! I think FM, ME/CFS, POTS and EDS (and some other conditions as well) have overlapping symptomology, as they are all realms of pain and fatigue. Dr. Peter Rowe, who investigates chronic fatigue in children happened to stumble on the fact that a large percentage of his patients also had EDS and forms of dysautonomia. About 80-90% of EDSers have chronic pain (both myopathic and neuropathic) and also about 50% have small fiber neuropathy. Fatigue and PEM is also exceedingly common in EDS.
I understand that researchers need to put artificial boundaries around the maladies that people experience, but in reality it is rather a ‘flow’ between all these named conditions. Personally, I think that the fall back position in scientific explanations, at least for fibromyalgia, is mental causation/treatment (think CBT or ‘flower arranging’) or central (sensitization), which is another way of saying that they really don’t understand exactly what is going on.
I’m glad that at least with “ME/CFS” they are starting from the ground with basic research and working their way up rather than glomming on to some favorite theory and using treatments that don’t work very well–as in fibromyalgia. Unfortunately those of us with CFS don’t really have any treatments–at least yet! But hopefully I think we will get there and in doing so, all these ‘sister maladies’ will also benefit.
I never met any Lake Tahoe Mystery Illness patients who had FM.
Notice that Dr Peterson says FM is different than CFS.
But Dr Cheney’s landlord, also an MD, said he had fibrositis from a combination of mycoplasma and bartonella.
He told me “Cheney and Peterson are idiots. The Lake Tahoe disease is a classic outbreak of bartonella”
Since I had the striae on the abdomen, which is consistent with bart, I wasn’t about to argue with him.
No CFS researchers ever looked into this.
But that’s understandable, as no CFS researchers ever looked into the Lake Tahoe outbreak at all.
Yes, I know they told you that they did.
They lied. All of them.
Actually it’s not true that no researchers ever looked into the Lake Tahoe epidemic. Whether or not they looked completely is another question but several studies did include Lake Tahoe patients in them
https://www.ncbi.nlm.nih.gov/pubmed/1309285
https://www.ncbi.nlm.nih.gov/pubmed/2824604
I think there can be a sort of cult-like thinking in different areas.
I certainly came across this in counselling and psychotherapy. Try challenging an authoritarian psychotherapist!
No don’t, just walk away for your own sanity ?
What I meant to include is a reference to a fascinating book called The Power of Others by Michael Bond.
He sheds light on the unseen forces in play between people and groups of people.
He puts in one book many ideas I’ve come across, when trying to understand what stops people intervening when they really should.
Very disappointed to hear this. As an ME/CFS sufferer and support group leader, I am delighted to see funding and research improving for my disease, but disappointed to hear that FM sufferers, who are in similar, if not overlapping, situations, are losing research support. I guess all we can hope right now is that the FM community gains recognition and that CFS research benefits the FM community as well as the CFS community.
Thank you for pointing out this unfortunate situation.
“Plus, while ME/CFS research is trending in the right direction – towards more pathophysiology – FM research appears to be going in the opposite direction, towards a more behavioral/psychological interpretation of the disease.”
You are missing the most important study on FM by David Andersson at Kings college, showing definitively the pathophysiology of FM.
Goebel, A. et al: Passive transfer of fibromyalgia pain from patients to mice. bioRxiv 24 July 2019. (This is a prepint article and cannot be re-used without the author’s permission).
Or view at InvestinME:
http://www.investinme.org/IIMEC14.shtml
Now we don’t know what triggers the autoimmune antibody production and it may well be infection or chronic pain but it could also be other forms of physiological stress. I doubt that it is triggered by psychological stress. Unfortunately it is so easy to relate a current set of symptoms to historical events in a person’s life. This is cheap psychology! Every PCP does it and it is a very bad habit born of ignorance. Thank goodness we have some psychologists who debunk this sort of nonsense. Eg. see the way The Journal of Health Psychology handled the Pace trial critique. (Thank You David Marks – ed)
The pathophysiology that joins these two conditions (in many cases anyway) is the autoimmune interference with the TRPM3 ion channnels. In fact this same pathophysiology underlies MCS as well. We have David Andersson to thank. He is now doing the same for ME/CFS and I believe he will nail it in the same way.
I guess that study didn’t show up in the last 20 citations on PubMed but thanks for the reminder of that fascinating study which I had forgotten about. 🙂
I just watched the Andersson lecture on FM pathophysiology which was fascinating. Is this the first time a FM model has been successfully produced?
Andersson’s FM study caught the attention of Dr. Fluge who wonders if replicated in ME/CFS, as Ian points out could happen, then might the findings tie into Ron Davis’ work? These are an examples of much needed international collaborations and the synthesis of various research findings. Very much like your article’s list format, they’re easy to read. Might you add Emerge Australia and Japanese research to them?
Sarah, the IIMEC14 presentation by Bevan (pain specialist working with David Andersson) might shed light on your question.
I also just watched David’s presentation. This is fascinating! Once again clearly proving fibromyalgia is not a psychological disorder. Thank you to whomever posted!!
If more advocates and charities got behind the use of ICC we might be much further forward. This is a good place to start for proper info: https://www.meadvocacy.org/calls_to_action
Understanding ICC as being the best way forward might help: https://www.meadvocacy.org/calls_to_action
Building upon some recent research and ideas I made an attempt to “reunite” FM and ME and bring them both under the nominator “neuroimune disease”.
Take in mind it’s still a fairly new hypothesis and needs some work on it. But as it fits well here and with a few recent blogs, I decided for once to write a long post on a half baked idea.
It probably is somewhat in line with “Passive transfer of fibromyalgia pain from patients to mice” from David A. Andersson too.
https://www.healthrising.org/forums/threads/potential-linking-fm-mast-cells-sleep-deprivation-food-intolerance-exercise-intolerance-and-me.6217/
Central sensitization does not really originate in the brain. This is the value of Andersson’s work. The peripheral nerves nociceptor threshold is lowered. If you look at more of Andersson’s work it includes a lot on TRPM3. In Australia Staines, Marshall etc have shown that TRPM3 is dysfunctional on many cells, most notable on NKcells. Their work excludes FM quite deliberately so that they can narrow the symptoms of the cohort.
“C” says that they are “similar but no way comparable”. On the contrary they are very difficult to tease apart and at Griffith it was difficult to exclude FM from their cohorts and I don’t know that they actually achieved that. I know of many people who started out with a diagnosis of FM but had it changed to CFS. (But they still fitted the criteria for FM). Some think that ME/CFS is much worse than FM, perhaps in extreme cases it is but in most cases both are similarly debilitating. People with FM diagnoses suffer from PEM. People with CFS diagnoses suffer from pain incl allodynia and neuropathic pain.
How do we explain microglial activation? Is that no the source of central sensitization? Is central sensitization not arising from NMDA dysfunction in the amygdala. These phenomena do cause questions but there is not reason not to suppose that these brain phenomena are secondary to the onslaught of faulty signals from the periphery and the DRG.
TRPM3 is exceedingly complex and has many variants. To have a theory which encompasses both FM and ME, you need a very low level dysfunction which creates varied symptoms within and between people. The mix of genetics is sufficient to explain, roughly the differences between FM and CFS but remember FM and CFS are just diagnoses/labels. Labels and diagnoses tend to put things into slots where no slots exist.
TRPM3 also co-activates (turns ON and turns OFF) sodium ion channels as well. It is the one TRP channel that has this broad effect. It is also co-linked to TRPM8 and TRPM4. All associated with chemo-sensitivity and sickness fatigue.
Thanks for sharing your ideas Ian.
“Central sensitization does not really originate in the brain. This is the value of Andersson’s work. The peripheral nerves nociceptor threshold is lowered. If you look at more of Andersson’s work it includes a lot on TRPM3.”
I to do believe that central sensitization does not really originate in the brain. Yet, we can’t select our “truths” and turn a blind eye to the quoted research that did find “Increasing the glutamate levels in the insulas of rats resulted in increased sensitivity to heat and pressure and – a reduction in the nerve fiber density in the rodents’ hind paws.”
Therefore I launched this hypothesis. It might explain the nerve fiber density reduction and an increase in pain sensitivity. While I see value in the TRMP3 path and will dive deeper into Andersson’s work, I don’t see yet how that explains the nerve fiber density reduction. If I understand correctly, the TRMP3 changes he observed trade an increase in cell survival rates for a decrease in ATP production. That IMO should protect nerve cells rather then trim them.
I believe there is place for both ideas and causes to contribute to increased sensitivity: long term toxin dumps from the immune system (and the brain interferes with the immune system) on the one hand and TMPR3 problems on the other hand. In fact I believe that is even only part of what escalates the problems to huge proportions as we see in the worst affected patients.
So IMO I would rephrase your quote to “A *large or even the major portion* of central sensitization does not originate in the brain. This is the value of Andersson’s work.”
“I know of many people who started out with a diagnosis of FM but had it changed to CFS.”
I too , having CFS and FM diagnosis, for long thought that my worst disease of the two is ME. But recently I started to wonder if my ME isn’t the result from my FM keeping assaulting my brain and showering it will all kind of inflammatory and toxic stuff plus derailing blood flow to the brain. After all, part of the early symptoms in my gradual onset case were extreme pain throughout my body. If so, dealing with my disease should require more attention to the FM part of it.
“How do we explain microglial activation? Is that no the source of central sensitization? Is central sensitization not arising from NMDA dysfunction in the amygdala.”
Well, the microglials and amygdala are IMO located in the brain so this quote puts IMO limits on “Central sensitization does not really originate in the brain.”
But looking for “microglial activation glutamate” gives a rich list of links. It seems that microglial activation can dump plenty of glutamate and that glutamate can activate microglial activation. That in itself, if correct, is prone to start a vicious circle.
The most clear link I did found was http://accurateclinic.com/wp-content/uploads/2018/05/Minocycline-a-Tetracycline-Derivative-Is-Neuroprotective-against-Excitotoxicity-by-Inhibiting-Activation-and-Proliferation-of-Microglia-2001.pdf
“Herein, we show that stimulation of glutamate receptors induces an activation and robust proliferation of microglia, which subsequently releases IL-1β and NO. This leads to neuronal cell death. We also demonstrate that glutamate-induced microglial activation occurs through the p38 mitogen-activated protein kinase (p38 MAPK) pathway”
There are other sources stating this too. But granted, it is complex as some other glutamate receptors have the opposite effect. Again I believe there are several possible pathways at work when it comes to microglial activation.
Histamine (and its relation with estrogen) has also a strong effect on the amygdala:
“”Histaminergic pathways:
… …
TMN → Amygdala”
That can add on top of the NMDA receptor problems over there.
“TRPM3 also co-activates (turns ON and turns OFF) sodium ion channels as well.”
Those sodium channels play an important role in glutamate excitotoxicity and that combines with hypoxia / ischemia / glucose problems that are often mentioned in combination with ME.
http://jpet.aspetjournals.org/content/285/1/178
“In our study, we have examined the relationship between oxygen/glucose deprivation-induced changes in extracellular glutamate/aspartate level and subsequent neuronal injury by pharmacological manipulation of glutamate receptors and calcium and sodium channels.”
Note: I am NOT saying that glutamate problems are at the core of our diseases but they seem to likely take part in the complex chemistry surrounding and “creating” our diseases. And so seem TRPM3 channels too.
I have mutation on 5 of the TRMP3 snps connected to FMS in the study.
There is some connection with TRMP3 and glutamate.
https://www.ncbi.nlm.nih.gov/m/pubmed/21955047/
Connections of TRMP3 and glutamate
Pregnenolone moderates this conversion.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2011.07441.x
Journal of NeurochemistryVolume 119, Issue 3
ORIGINAL ARTICLE
Activation of steroid‐sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats
Paula A. Zamudio‐Bulcock Julie Everett Christian Harteneck C. Fernando Valenzuela
First published: 22 August 2011
https://doi.org/10.1111/j.1471-4159.2011.07441.x
Cited by: 34
Address correspondence and reprint requests to C. Fernando Valenzuela, MD, PhD, Department of Neurosciences, MSC08 4740, 1 University of New Mexico, Albuquerque, NM 87131‐0001, USA. E‐mail: fvalenzuela@salud.unm.edu
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Abstract
J. Neurochem. (2011) 119, 474–485.
Abstract
The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. In this study, we demonstrate the abundant expression of TRPM3 steroid‐sensitive channels in the developing cerebellar cortex. We also show that TRPM3‐like channels are expressed at glutamatergic synapses in neonatal Purkinje cells. We recently showed that PregS potentiates spontaneous glutamate release onto neonatal Purkinje cells during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3‐like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3‐inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.
I think the possible connection with TRMP3 and MCAS is through the calcium channels. Two of the medicine I find most beneficial for MCAS and POTS have mild calcium channel blocking properties. Both vasodilate. Here’s article listing TRMP3 to MCAS.
https://www.frontiersin.org/articles/10.3389/fimmu.2012.00150/full
So both things may be closely connected and another piece of the puzzle. Like the 3 blind men and different parts of the elephant. All described each part, but all connected and same animal.
And here is another link. I’ve been trying to find connections between calcium channels and glutamate channels NMDA for years. There are some good links here with connections. (I don’t think my friend Ken will mind me listing his site here.)
Calcium Channels and CFS? | CFS Remission
https://cfsremission.com/2017/03/14/19555/
Wow, way to start a controversy, Lol. Agreed, this was a difficult position to digest and different type of comparison to understand when sooooooo much work has been put to getting Anywhere with research progress for ME/CFS. How many FM patients are housebound and have no voice? Decades, decades of going nowhere with ME/CFS issues/symptoms, little more than a brush off from all 8 docs and specialists that I’ve seen, one who really cares but still doesn’t understand. So many patients lost and hurt and the article seems to compare that FM should get some better traction on its research? They are similar but in no way comparable. It seems until 2019, one cannot receive a simple diagnosis or recognition that someone with CFS is anything but “oh you’re tired and depressed ” so sorry”. ME needs the diagnostic criteria right? Isn’t that what we are all striving for? So we can find doctors that have heard of the illness and maybe even one that acknowledges some appropriate care plans?
dejurgen. I take your comments to heart. However:
Not all people with FM have reduced small fiber density
nerve fiber density reduction is most notable in diabetes
From notes from some of my colleagues nerve fiber density reduction in FM (some) may also be associated with elevated HbA1c as it is in diabetes.
However, I am fairly sure that excitatory inhibitory neurochemical imbalance may play a role in FM. It must! Pain is a complex process.
FM is a “chronic ” pain condition, which means that the pain controlling areas of the brain are going to respond to the onslaught. One is the insula but the other is the Nucleus Accumbens, which has significant role in “chronicity” of pain. This also an area of errant glutamatergic activity in response to pain. In addition, other areas involved in emotional effects of pain such as the amygdala are involved. I agree: looks like changes to glutamate chemistry do add to the complexity of the illness – and what a complex illness it is. Like any complex illness so many things can be affected.
For me, there are too many factors involved in pain processing to work out what is going on.
Just to complicate it, the TRPM3 contains a recognition site for miR-204 which regulates various target genes at the transcriptional level. miR-204 serum levels correlate with lumber originating pain in lumbar disc herniation ( a common problem). In addition it is well known that people with FM have more problems with low back pain. Also recalcitrant low back pain after surgery is more associated with FM than any other pathology. This is important because for a long time it was not known why some people have continued pain but others do not. Patients who improve after surgery have much lower levels of miR-204.
The point is, that the “effects” of TRPM3 variant dysfunction is highly complex and widespread and much unknown. I suspect there is also a relationship between TRPM3 and arteriolar shunting because TRPM3 induces vasoconstriction in murine arteries.
ENDOTHELIAL TRPV4 DYSFUNCTION IN A STREPTOZOTOCIN-DIABETIC RAT MODEL
https://pdfs.semanticscholar.org/a69f/0b951dbc6f4253e20c1c3c06304e6c774c9e.pdf
David andersson has also shown that TRPM3 nociceptive function can be modulated by GPCreceptor activation. This has been shown to occur in the Dorsal root ganglia.
G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons
https://elifesciences.org/articles/26138
It will be very interesting to see the effects of such GPCr activation in FM patients, if and when it can be done. I suspect that pain in FM will subside and the associated microglial activation subsides too.
Thanks Issie for those references and notes.
Hi Ian, thx for the input!
“nerve fiber density reduction is most notable in diabetes”
“nerve fiber density reduction in FM (some) may also be associated with elevated HbA1c as it is in diabetes”
That makes for an interesting combination. After looking it up HbA1c appeared to be https://en.wikipedia.org/wiki/Glycated_hemoglobin. And that sounds oddly familiar to AGE (Advanced Glycolation End products). And https://en.wikipedia.org/wiki/Advanced_glycation_end-product creation speed is increased with both higher blood sugar levels and higher amounts of ROS.
ME patients have higher average blood sugar levels (with big swings on it). I don’t know about FM patients. And ROS seems to be very present in both conditions. Immune activation including MCAS would be a “good” source of elevated ROS, as is the Dauer inhibition too.
The problem is, glycolated hemoglobin by itself increases blood viscosity, inflammation, free radicals and ROS. So it offers the potential to cause a vicious circle.
Also “Highly glycated Hb-AGEs go through vascular smooth muscle layer and inactivate acetylcholine-induced endothelium-dependent relaxation, possibly through binding to nitric oxide (NO), preventing its normal function. NO is a potent vasodilator and also inhibits formation of plaque-promoting LDLs (i.e. “bad cholesterol”) oxidized form.”
Low NO and blood vessel constriction are known problems in ME/?FM?. Together with plaque formation in blood vessels in combination with high blood viscosity, unflexible RBC and often low blood volumes could contribute a lot to (very) poor blood flow in the smallest capillaries, contributing to time and location depended hypoxia (and toxic glutamate dumps?) in ME/FM patients.
Maybe that would be another factor in why ketogenic diets often are helpful in ME/FM?
In addition, I would not be surprised if these “AGE”s, promoted by high oxidative stress, increased average glucose levels and increased HbA1c would also form into the fascia, potentially cross-linking parts of the fascia that are supposed to move against each other. I wonder if that could be part of Philip Hayward’s famous “lumps” in his fascia. Would love to hear thoughts on it of either of you.
“However, I am fairly sure that excitatory inhibitory neurochemical imbalance may play a role in FM. It must! Pain is a complex process.”
Thx for your opinion to this. Where I only grasp the very basics of ion channels (autodidact in medicine only), I am a good (system) engineer and know that in many cases one can stabilize an unstable system by dealing with only part of the feedback loop. And the potential glutamate toxicity escalation is one thing that can be dealt with by low-tech IMO. Safely and reliably changing ion channel behavior is out of my reach :-).
So while I agree with “For me, there are too many factors involved in pain processing to work out what is going on.” a lot, I am happy to find a partial mechanism that I can deal with :-). I dislike waiting another decade plus for effective medicine.
By bringing up the theme of https://en.wikipedia.org/wiki/Glycated_hemoglobin and it’s many negative aspects to (ME/FM) patients health you got me thinking further.
Another place where heme, glucose and likely plenty of ROS in the case of ME patients come together are: the mitochondria.
Complexes III to IV in the electron transport chain are in effect hemes https://en.wikipedia.org/wiki/Electron_transport_chain “(redox intermediates in the hydrogen pumps as in heme groups of Complexes III and IV)” and the other complexes at least resemble them.
Glycolysation of these key complexes may not only hamper energy production, but further ramp up ROS production very high if the mechanism is even remotely comparable to what seems to happen in glycolated hemoglobin. The additional ROS would further increase glycolation of these complexes creating even a stronger vicious circle.
So I looked up if that would be a remote possibility. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595188/ with title “Multiple proteins with essential mitochondrial functions have glycosylated isoforms”
“Our findings indicate that glycosylation of classic mitochondrial proteins may be more common than previously appreciated.”
“knowledge regarding the glycosylation of mitochondrial proteins is limited”
“iron-sulfur protein 3 (NDUFS3, a Complex I subunit)”
=> the latter is an iron-sulfur containing protein that was found in glycolated form in the mitochondria in this study; iron-sulfur proteins have many similar properties to hemes IMO regarding to be able to create plenty of ROS when damaged.
=> So it seems to be a potential route for (deep?) trouble in ME/FM. Once more, a ketogenic diet would reduce glucose in the mitochondria a lot, reducing glycolisation.
Ian,
One of your links talks of TRMP3 as being vasoconstricting. It is also connected to the kidney and calcium channels. Having found I do better to vasodilate (despite having POTS) and also that two of my best medicine for POTS were GastroCrom and Tramadol. This is interesting as it ties in. (Both have mild calcium channel blocking effects and vasodilate.) Further in a link, I think by dejurgen, it list an experiment with morphine an opioid. That too has bearing on the workings of this gene/channel. I’ve often said, we have opioid receptors and they do play a part in pain. My tweaking that receptor gives me more results than cannabinoid receptors. (However, I’m on my off cycle of both Tramadol and Bentyl and have been off for 3 weeks now. With new things I’m doing, my pain is no worse off them than on them and my POTS is staying at a low roar. I however, didn’t take enough to help pain but to calm down the autonomic nervous system. Absolutely, no withdrawals from pulsing these two things.)
There are ways to tweak these mutations (if they are causing dysfunction). But just because there may be a mutation doesn’t mean some assister genes haven’t stepped in to help and this may not even be a problem.
But with connections to glutamate and calcium channels, I’m mostly tweaking glutamate right now (however, Tramadol also works on NMDA/glutamate channels as well as calcium channels too). So far, this is keeping things level enough for me to not feel I need to go back on them right now. Except for mast cell issues and need with the GastroCrom, that’s mostly as needed. However, I’m not using H1 and H2 regularly for MCAS either and that is a major miracle for me. But I’m having to be strict on my diet and paying attention. I am however using an H3 that works on brain level histamines and affects GABA and possibly glutamate. I’m doing some other things too. So far, no paradox or ill affects.
It is all so complex and one thing leads into another area and it’s hard to sort just what is key. As dejurgen said, for me, tweaking glutamate seems to be making a positive impact.
There is still so much to learn. We are so wonderfully made. Our grand Creator is a Master.
Chronic Pain | Life Extension
https://www.lifeextension.com/protocols/health-concerns/chronic-pain/page-01
I just received this article and it has alot of good suggestions on chronic pain. One of my new tweaks is in there and does seem to be helping me. I’m using PEA. The one suggested to me also has lutolin in it and that helps with MCAS too. Has to be front loaded and is not cheap.
I skimmed thru most of the comments. Just wondering if anyone has tried Nootropics which I just read an article about. They’re supposed to help with the brain fog, mood swings and blood flow in the brain AND they’re available without a prescription. I’m nervous about experimenting as I’m so overly-sensitive and have had bad reactions to so many meds as well as supplements.
Those are also “ify” and can be okay for one and not another.
I’m SUPER sensitive to things and have alot of paradox reactions. But what I’m doing now, I’m seeing huge results from. Still too early to talk about. But watch thread dejurgen started and link he posted. My follow ups will be there.
Issie
This study reinforces my point about the brain changes in FM being mostly a result of nociception.
Sundermann, B. et. al.
Subtle changes of gray matter volume in fibromyalgia reflect chronic musculoskeletal pain rather than disease‐specific effects
European Journal of Neuroscience. 2019;00:1-10
“In conclusion, we did not identify significant and FMS‐specific GMV alterations when adopting a conservative statistical approach of multiple comparison correction. However, with a more liberal approach increased gray matter volumes in the sensorimotor cortex and decreased GMV in the tem-poroparietal junction in both pain groups in comparison with healthy controls were revealed. Since both pain groups showed nearly identical GMV changes in these areas, cortical GMV changes in FMS should not be interpreted as FMS‐specific but might rather reflect changes in chronic pain in general.”
In simple terms there are three compartments: periphery, spine/spinal fluid and brain. If the spinal system, eg. DRG is not modulating pain signals then consistent high level signals will evoke all manner of “central” responses. One thing David Andersson did not find were the IGg auto-antibodies in the spinal fluid and this suggests that the TRPM3 receptors in the brain are not attacked so the changes in the brain may as Sundermann’s study suggests be the result of continuous elevated pain signals. A horrible unethical experiment would be to subject rats to continuous pain and see what happens in the brain. No I did not suggest that.
The impact of fibromyalgia symptoms on brain morphometry. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/26615599/?i=2&from=/31448468/related
This one was listed below the one you list. Never knew pain could affect the actual structure of the brain. Interesting to me. As my worst symptom is pain. And I have changes with brain structure. I wonder if getting pain better under control, would cause brain structure to increase where it needs to and decrease where it may be “swollen”. They look at brain structure in mold illness and connect both atrophy and swelling to inflammation to that. But, of recent are thinking there may be more to it. As some don’t respond to mold treatments and it is now thought Lyme may be playing stronger connections. And I wonder about Funneliformis mosseae that Dr. Fry found in both blood and thyroid biopsy. All of which have been a problem for me.
Well I took buprenorphine as a patch for 9 months. During this period I had no pain whatsoever. My gut function improved (although a little constipation consistent with opioids). My balance improved. My fatigue dissapeared and had no PEM and I slept well. Unfortunately I started having blackouts and had to quit the drug. I now know that most opiates will cause syncopy in me. (except tramadol) Tramadol only reduces my pain about 50%. So yes I think that if you can eliminate all pain for a long enough period I think the brain may recover. However these drugs have effects on brain function – so its not quite that neat. I await the new drug AT121. but maybe we will have an immune system solution too.
Tramadol and Bentyl had been my best POTS medicine. They helped calm my Hyperadrendic response down. I’ve been off those for a month now and trying to use herbals and other supplements. I didn’t take enough for it to help pain. But it did take the edge off. Working on tweaks to lower glutamate and balance between glutamate and GABA. So far, helping. But don’t have it all figured out yet. Still working on dosages.
I’ve often felt since there are opioid receptors in our body, same as cannabinoid. If cannabinoid can be off and not functioning properly, why not the opioid receptors. I don’t do well well supplements for cannabinoid but do with opioid receptors. There are some herbals (that can be gotten in health store) that work on that receptor too.
Also, since I have severe MCAS. Trying to manage this without antihistamines and doing it with diet and a few select supplements. Really, don’t have that one figured out yet. But getting closer.
Maybe we are the “mice” and the study with our brains atrophying and swelling are proof positive to this.
Poor little mice, all to tell us what may or may not be going on with us. No Ian, you didn’t say it out loud, didn’t hear it. 🙂
To all our fibromyalgia friends – we are making our comeback! Advocacy Day complete and more to come. Thank you Cort for this great blog and outline. We’ll be checking off the boxes and reaching out to the ME/CFS organizations as well. Stay tuned! – Mel #SupportFibromyalgia
Thanks Melissa! Looking forward to hearing more. Good luck and please let me know how I can help 🙂
One of the other things to consider about the IGg mediated autoimmune cause of FM is the much higher incidence among females. This is consistent with the illness being mediated by IGg because women have much higher levels of IGg auto-antibodies in general. It may be that FM is a pathology of IGg auto-antibodies rather than a specific problem with the nociceptors or other TRPM ion channels. I am suggesting that it is an aberrant melastatin protein which the auto-antibodies are trying to modify ie the ion-channel is the “fault” but it might not be. It may be that the ion-channel is being modified by the auto-antibody.
In a recent study in the Journal of the American Society of Nephrology by researchers at the University of Alabama at Birmingham the role of IGg auto-antibodies in kidney nephropathy has been identified but its not what you might think:
Patients with IgA nephropathy have elevated levels of circulatory galactose-deficient IgA1; This leads to development of autoantibodies, mostly of the IgG subclass; The IgG autoantibodies bind galactose-deficient IgA1 to form pathogenic immune complexes; Those pathogenic immune complexes deposit in glomeruli to incite kidney injury.
So here we see a complex immunoglobulin causing damage. Normally many IGg auto-antibodies have a clean-up role in the body and bind with “ill-formed” proteins but it appears that when they do a problem can be the result.
So what would this indicate with someone like me with Hypogammaglobulinemia? Way too low IGG.
Is your deficiency genetic?
Are you on IGg replacement therapy?
I don’t think there is any relationship to FM or ME/CFS except that you would be more prone to infection or the effects of infection.
The point I was making was a population difference between males and females
Genetic. Was offered IVIG, but seldom get sick (colds, flu) and didn’t want to take risk associated with IVIG. Yet still have autoimmune issues and no ability to fight pneumonia.
Issie