Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?Jo Nijs,Marco L. Loggia,Andrea Polli,Maarten Moens,Eva Huysmans,Lisa Goudman, Expert Opinion on Therapeutic Targets Volume 21, 2017 – Issue 8 .
The implications of the widespread nature of central sensitization (CS) are potentially enormous. If someone cracks the central sensitization “code” in arthritis, it’s possible a similar code may apply to fibromyalgia or chronic fatigue syndrome (ME/CFS). With fibromyalgia getting so little research money, treatment breakthroughs in FM may very well depend on work done in other diseases.
The fact that CS is widespread is good news for FM and ME/CFS patients because the situation is complex. The sensory processing issues found in FM are associated with problems in many different areas of the central nervous system including the spinal cord, thalamus, insula, somatosensory cortices, anterior cingulate, prefrontal cortex, and brainstem.
The Source of Central Sensitization?
The increased pain sensitivity in FM could all come down to immune cells in the brain called glial cells (microglia, astrocytes, and oligodendrocytes). Despite the fact that glial cells are much more common than neurons, they were all but ignored until about 10 years ago. They’re being ignored no longer. When activated, these cells pour out inflammatory factors that tweak the pain pathways, clean up cellular debris and kill pathogens.
When they’re turned on full-time, glial cells can have pathological effects. They’re linked to pain sensitization because they emit many factors (brain derived neurotrophic factor (BDNF), IL-1B, TNF-a) known to send our pain-producing nervous system pathways into a tizzy. When they’re turned on full-time, they produce a state of chronic inflammation found in many central nervous system disorders.
The role poor sleep may play in activating these bad players isn’t being ignored either. Poor sleep, it turns out, appears to bring out the worst in our glial cells.
The great question, though, is how these glial cells get chronically activated. The authors come down to the great catchall, “stress”, which can denote anything from an infection to emotional stress. The authors note that the kind of stress is not the issue; it’s the fact that some sort of stressor is continually present that matters.
One kind of unrelenting stress often found in ME/CFS and FM involves chronic sleep issues. In fact, stress, sleep, and pain often form a positive feedback loop; chronic pain produces stress which hampers sleep, which, in turn, leads to more pain, more stress, poorer sleep and so on. Just a single night of poor sleep results in increased pain sensitivity and anxiety even in healthy people. Given that fact, it’s perhaps no surprise that no less than 50% and up to 90% of chronic pain patients struggle with insomnia.
As was noted in a recent blog, sleep deprivation results in a low level inflammatory response which produces the same kinds of factors that microglia spew out when activated. This suggests that sleep deprivation, or insomnia, or sleep apnea or any other sleep disorder may, in some cases, actually be able to initiate the central sensitization process; i.e. tip some people into FM.
Neuroinflammation
Being able to detect low-levels of inflammation in the brain has been a goal for many years. Different approaches are being used, but recent studies using the [11C]-(R)-PK11195 positron emission tomography approach have found neuroinflammation in the basal ganglia in complex regional pain syndrome (CRPS), in the hippocampus in Alzheimer’s, in Parkinson’s and in multiple sclerosis.
We know that neuroinflammation can produce pain, fatigue, hypersensitivity to stimuli, etc. But is it actually present in chronic fatigue syndrome (ME/CFS) and fibromyalgia? The jury is still out on that question.
A Japanese PET scan study succinctly pointed out the problem – lots of speculation – not much evidence.
“Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME.”
That Japanese study, which was the first to present direct evidence of neuroinflammation, excited many in the field, including Dr. Komaroff, who called it the most important ME/CFS study in years. The study concluded that:
Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.”
It seemed that we were really onto something and, indeed, Shungu’s findings of increased lactate and/or decreased glutathione in fibromyalgia and chronic fatigue syndrome appear to be pointing an arrow at neuroinflammation,. It was very good to see Glassford’s hypothesis paper link neuromuscular issues with neuroinflammation in ME/CFS – nobody has done that before – but what we really, really need are neuroinflammation studies.
Unfortunately, science tends to move very slowly in ME/CFS, and that small 19-person Japanese study, published in 2014, three years later still remains the only direct evidence of neuroinflammation in ME/CFS.
Currently, the Japanese, Andrew Lloyd and Jarred Younger (funded by the SMCI) are all, reportedly, doing neuroinflammation studies. The Japanese study has taken three years to get started but it’s a big one – 120 patients – and should go far to resolve this issue. It’s not clear if the NIH Intramural study has taken up this issue, but it would be surprising if it did not.
Fibromyalgia
A cerebral spinal fluid and blood study pointed an arrow at neuroinflammation, but I have yet to find direct evidence of neuroinflammation in FM. The lack of studies is surprising given how clearly the central nervous system has been implicated in FM. (Both that study and Younger’s early results in ME/CFS highlighted fractalkine. If Younger’s early findings pan out, he may have uncovered a ME/CFS/FM subset.)
The New Sleep Agents?
“It’s not about what the FDA-approved treatments directly target. Fibromyalgia is about neuroinflammation in the central nervous system [CNS]. The key to treatment is to reduce that inflammatory process in the brain. We have to discover and employ both pharmaceutical treatments and other interventions that can get to the CNS and target the cells that drive the inflammation.” Jarred Younger
If glial cells play a major role in the pain and sleep issues found in fibromyalgia and other chronic pain conditions, then glial cell inhibitors, not sleep drugs, may be the best answer. Drug companies are purportedly working hard on developing the next generation of anti-glial cell drugs. Human trials are underway for some substances; many others are being tested either in animals or in the lab.
One of the most interesting drug combinations was identified by combining a complete list of available drugs with a computer program containing research results from ME/CFS. The drug combination highlighted contained two potential glial cell inhibitors – trazodone and low dose naltrexone.
Below are some of the drugs being tested.
The Future Sleep Drugs? Possible Glial Cell Inhibitors
Drug Trials
- Minocycline – is an antibiotic which has been shown in animal studies to suppress glial cell activity. Interestingly, it seems to do so at least in part by activating endocannabinoid (cannabis) receptors, suggesting that cannabis and minocycline might work well together, which brings us to….
- Cannabidiol – the major constituent of cannabis, cannabidiol has been shown to reduce glial activity. The clinicaltrials.gov website brings up over 50 cannabidiol studies underway or about to get underway on chronic pain, inflammatory bowel disease, cancer pain, spinal cord pain, motor neuron disease, Tourette’s syndrome and others. None of them mention glial cells, but the large number of studies underway is good news. The federal government still puts cannabis in the same category as heroin and LSD, but has relaxed restrictions on studying it. Successful trials will force the federal government to remove cannabis from its current designation.
- THC – high THC or tetrahydrocannabinol cannabis is simply the best sleep medicine I’ve taken. Several THC studies are also underway including those on low back pain, nausea and vomiting in dysautonomia, Alzheimer’s, cancer and epilepsy.
- Low Dose Naltrexone (LDN) – several small studies suggest LDN can be helpful in FM. Jarred Younger has expanded those studies to include ME/CFS and is examining the effects of different doses as well. I believe he is also determining if LDN effects neuroinflammation using his brain temperature testing protocol.
- Propranolol – a beta blocker, has, interestingly enough, been shown to be taken up by glial cells.
- Ketamine – Ketamine’s ability to reduce pain and/or depression has made it a hot item; many studies are underway in chronic pain, depression, autism, sickle cell anemia and others.
- Dextromethorphan – several studies of dextromethorphan’s effect on pain are underway including Jarred Younger’s FM trial.
- Naltrexone – several studies underway, one of which (Younger) may be assessing neuroinflammation before and after treatment.
- Ibidulast – is an anti-inflammatory drug used mainly in Japan to treat neuropathic pain and asthma. It has neuroprotective effects. Ibidulast recently reduced neuroinflammation in a mouse model of Parkinson’s disease. Four trials are currently underway.
Lab Studies
- Trazodone – decreased pro-inflammatory cytokine production by astrocytes in the lab.
- Moclobemide – antidepressant reduces glial cell activity.
- Imipramine – antidepressant reduces inflammation and glial cell activity.
- Tangeretin – flavonoid reduces inflammation in glial cells.
- Fucoidan – reduces inflammatory production by glial cells.
- Bee venom (melittin) – suppresses inflammatory activity in glial cells.
- Anti-inflammatory Diets – low fat, low sugar, low calorie, low-glycemic index diets.
Conclusion
Glial cell inhibitors are being developed. Time will tell whether they’ll be able to help or even eliminate the pain, sleep, fatigue and other issues present in ME/CFS and FM, but if the hypotheses around ME/CFS and FM are correct, they should.
Whether neuroinflammation plays a major role in these diseases is still unclear, however. The research is moving slowly, but with two studies and probably a third neuroinflammation study underway in ME/CFS, we should know more over the next couple of years. Unfortunately, and rather amazingly given the fact that fibromyalgia is the poster-child for central sensitization, I was unable to find any studies assessing neuroinflammation in FM. (Jarred Younger may be doing one.)
Check out Sleep Resources on Health Rising including the latest:
- The Lifesaver – how a simple, cheap tool helped one person finally get some sleep.
I take Trazadone for sleep, and it was my understanding that this is a glial cell inhibitor also. I also take LDN.
Thanks for that mention. Trazodone is a really interesting drug. When I looked it up I realized that a group had identified a Trazodone-LDN combination as potentially very fruitful in ME/CFS – https://www.healthrising.org/blog/2016/02/04/low-dose-naltrexone-combo-chronic-fatigue/
LDN is a putative glial cell inhibitor as well.
Yes, I remember reading that. Thanks Cort
I take MMJ and my inflamation and pain goes away except for the base of my skull headaches.
https://www.karger.com/Article/PDF/338049
Appears Tramadol can affect glial cells also. So far is my best help for POTS. I don’t use enough to really help pain. But for whatever reason this helps some and helps with sleep. I also find that it along with Bentyl – mild muscle relaxer helps best. (Though I don’t use this regularly as it can be a depressant.)
Trazodone is one of the more interesting drugs out there. From a blog – https://www.healthrising.org/blog/2016/02/04/low-dose-naltrexone-combo-chronic-fatigue/
Trazodone is probably also used more as a sleep aid than as an antidepressant in chronic fatigue syndrome. (As with LDN, lower doses than usual are used to improve sleep.) It’s one of the few drugs (Xyrem is another) able to reduce the activity of the alpha waves known to hamper sleep in fibromyalgia.
A 2011 open-label FM study found that Trazodone significantly improved sleep quality, duration and efficiency. The authors called the increase in sleep quality ‘striking’. Another 2011 fibromyalgia trial study found that Trazodone in combination with Lyrica (pregbalin) improved pain, anxiety and morning stiffness.
The IACFS/ME Treatment Primer reported that Trazodone might be able to maintain its effects over time better than any other sleep drug. Dr. Bell and Dr. Lapp both promoted Trazodone use, with Dr. Bell stated Trazodone was one his favorite sleep medications for sleep.
Neuroinflammation Reducer
A 2015 study suggested that Trazodone may be producing its effects in depression by reducing neuroinflammation. Neuroinflammation is common not just in neurodegenerative diseases like Parkinson’s, Alzheimer’s and multiple sclerosis but in depression as well.
In a mouse study Trazodone upregulated levels of BDNF – a brain growth factor. BDNF appears to play a critical role in pain sensitization and neuroplasticity. BDNF levels appear to be high in FM but low in ME/CFS.
Trazodone prevented glial cells called astrocytes, from spewing out pro-inflammatory cytokines when confronted with an inflammatory stressor. If Younger and Miller are right about microglial cells over-reacting to small amounts of inflammation, a drug like Trazodone could be beneficial.
It’s spelled Xyrem not Zyrem.
Interesting info about Trazadone, but you were replying to Issie’s post, which was about Tramadol (pain med).
My sis took Trazadone for years. She stopped. It caused her more fatigue. She took it to help sleep. She didn’t feel it was a “fix”. And both my sis and I paradox with anything that ups GABA. Instead of it being calming it gives us anxiety.
We are all so complex and our DX varied. We may have similar symptoms – but there isn’t one “fix”. This is too complex an issue with many facets.
Basically, faulty autoimmune system response and inflammation – presented in different ways. I stick to this conclusion.
Issie
Not a bad conclusion. It’s hard to believe that inflammation isn’t playing a role- and with the recent OMF Symposium – that autoimmunity isn’t either.
Trazadone made me so incredibly jittery and anxious. That effect scared me so bad. It was a low dose too. My body has opposite effects to quite a few medications. If I take more than a half a tablet of Benadryl I get jittery too, like restless leg syndrome. No one knows how to treat my sleep because I have different reactions than most people. Even several herbal sleep supplements make me feel jittery.
You experience Jenn is just a picture perfect example of how difficult treating these diseases can be – people have so many different reactions to drugs and supplements. I don’t think I’ve heard an explanation of why such low doses of drugs can affect us so much.
Glad to see things in the works that may help us.
Interesting to see Bee Venom here. A couple of years ago I had my best day all year the day after being stung by a bee. I read about Bee Venom Therapy, ordered a kit of pharmaceutical-grade bee venom from Sweden, but then couldn’t find someone I trust to administer shots. My acupuncturist and another acupuncturist who is also an RN both respectfully declined because it’s not part of their licensed protocols.
Dr. Chia was very excited to hear about my bee sting experience, but cautioned that I have allergy tests before doing anything. My allergist did blood tests and found that I am not allergic to bees but I am quite allergic to several wasps, probably relating to stepping on a wasp nest as a 4-year-old and being stung multiple times. So the allergist couldn’t offer BEE venom therapy–which is really the same protocol as allergy shots, starting with very small doses and increasing them incrementally, backing off on dose if one shows signs of allergy–but he could offer shots for my wasp allergy. And yes, the first wasp shot gave me that hoped-for boost that the bee sting had earlier that year.
But, long story short, we had to stop the shots because my allergic reaction to them didn’t fit the protocols! Instead of happening within the 30 min. allotted by these protocols. Instead of rapid on-set, I would develop hives in the arms over the next day or two, but week three hives everywhere. So basically, unless my presentation was within norms, I was no longer a candidate for treatment. Since the Naviaux paper came out, showing that we’re in a state of hypometabolism similar to hibernation, theoretically my my/our ability to deal with may be as blunted as out ability to work with metabolites, I’ve considered making my case to have the shots again. I’m certainly no less allergic to wasps than I was before, so they remain a danger to me. And yes, I’d hope to have a boost in health by having the dose stay lower for much longer before trying to increase!
Ha! One of the stranger recovery stories on Health Rising concerns someone who basically stung were way back to health….I guess it can happen…
https://www.healthrising.org/forums/resources/stinging-her-way-back-to-health.131/
Bee venom was on Jay Goldstein’s treatment algorithm. Didn’t help me back on the ’90’s but apparently did help many of his patients. Nothing new under the sun, I guess… ?
Hi Carollynn,
How do you react to nettle or ant stings? For some purposes nettle and and stings do have likewise but milder effects compared to bee stings. One can however be allergic to both. When it comes to ants, there’s a wide variety in their strength and composition of poison making it hard to standardize treatment. For nettles that’s less of a problem.
There’s also bee venom in ointments and for oral use. Allergic people should avoid them so knowing that before is important.
I did a bee venom therapy protocol with live bees for about a year. There were some benefits for me, but I had an autoimmune reaction to it and had to stop. Not allergic reaction, but autoimmune. Live bee venom therapy is a thing that you can do yourself at home
Bee venom has a whole slew of properties that are unique to it, way different than nettles etc. it’s not just the sensation of the “sting”, but the actual components in bee venom
What autoimmuneresponse did you have?
I take minocycline. It hasn’t cured me, or even honestly made me better. It is different. I feel different, I went down several ring sizes without losing weight. I am now trying to research starting a CBD (hemp based) supplement to see how that goes. I also take naltrexone and have for almost a year- it didn’t have any direct effects that I noticed at all, perhaps it is working in conjunction tho as I also have an autoimmune disease.
Good luck with the CBD supplement. I’ve found high THC cannabis to be VERY helpful with sleep.
I’ve heard from others who didn’t get much help from minocycline. I think the real boosts will come when we get drugs that are specifically created to reduce glial cell activity instead of finding already available drugs that might have that property.
Yeah I honestly would rather not be on an abx long term if they could find a better or new drug that is more effective for the specific mechanism! At least in the meantime its cheap and so long as I take vitamin c with it I won’t turn strange colors. It is interesting that my inflammation went down but I still feel really ill and am the same level of functioning in the end as I am without it. :/ fart noises. Ive heard some people fair better with LDN combining coq10 and i think NAC but i’d have to check on thst one- thinking of trying that too since theyre OTC
“…The implications of the widespread nature of central sensitization are potentially enormous. If someone cracks the central sensitization “code” in arthritis, it’s possible a similar code may apply to fibromyalgia or chronic fatigue syndrome…”
So shouldn’t an obvious hypothesis be that the CNS heightened state is BECAUSE OF chronic pain of musculoskeletal origin??????
At least with arthritis it is well understood what this real pain from real bodily tissue, is. But for goodness sake, focusing research on the CNS is like race-car mechanics trying to use the engine management electronics to fix a mechanical problem like blocked lubrication flows, overheating and excessive friction in the cylinders.
I want FM research to resolve the problem in my muscles, not my “head”.
Glial cells and the CNS aren’t “turned on full time” because of some dysfunction in the CNS itself, they are turned on full time because real pain from real “injuries” is present all the time!!!!!
“…the great catchall “stress” which can denote anything from an infection to emotional stress. The authors note that the kind of stress is not the issue; it’s the fact that some sort of stressor is continually present that matters…”
Well, duh, isn’t real pain from real injuries likely to be “THE” stressor?????
“…But is neuroinflammation actually present in chronic fatigue syndrome (ME/CFS) and fibromyalgia? The jury is still out on that question…”
Dejurgen (a commenter here) suggests a hypothesis that inflammation should be present in muscle tissue throughout the body, in FM, which would logically accompany the kind of pain we are in; but that this response is automatically suppressed because it would probably be fatal if it were allowed to proceed. For whatever reason, “researchers” prefer to ignore potential causes and cures in the musculoskeletal and biomechanical areas.
Certainly it is possible that something as prosaic as a toxic element is the catalyst for the problem in every single person with FM; naturopath Gary Moller states that Hair Tissue Mineral Analysis always reveals a high level of some toxic element, in people with FM.
But of course the dysfunctions of FM have long since become a cascade, a vicious circle, by the time this sort of diagnosis is happening. Then the cure is never as simple as dealing with one single factor, whether de-toxing the body or drugging the CNS. I have described the likely reversal of the vicious circle with a multi-disciplinary protocol many times elsewhere on this site.
🙂
Hi Philip,
That reminds me of tales of a common fifties practice: if a fuse blew to frequent, people often replaced it with a thick copper wire. Kinda worked ;-).
On a serious note, I do see value in the approach of the researchers for cancer treatment. There, sufficient effort is done to remove and cure the cancer first. Then additional care to reduce secondary effects like great discomfort and negative physiological effects caused by pain induced CNS deregulation is warranted. This research was not FM/ME specific.
If I recall correctly professor Nijs has worked on CFS before. This indirect route may however be a good strategical choice. FM/ME has proven far to flaky to built an entire research program around the effect of pain in FM on glial cells. Results are often hard to repeat. That can burn a researchers career. If there are no results then the researcher risks ending up with no publications and no future research funding. Then it gets tempting to rework questionable results into solid findings. Look what happened when the UK government gave 5 million pounds to prove that the cheapest treatment was also the most effective one… :-(.
By focusing on an established field and leaving the option to widen up to more challenging fields like FM/ME they allow themselves to only mention positive results for these diseases if they feel confident enough. They can chose how much focus to put on these diseases. That avoids publication of mediocre or debatable FM/ME research. That is especially important for a young field as other researchers tend to build on those early publications. Meanwhile these intermediate results add to the image of FM/ME as a real physiological disease and lower the bar for other established researchers of non-FM/ME fields to engage in our disease. Once the image of real physiological disease gets solid set in researchers minds they can explore what sort of problem causes the pain in the first place. What’s not to like safe that this is the slower route?
As I doubt we’ll get an accessible cure within one decade I prefer the combination of broad and fundamental research done by the OMF and others combined with this safe and indirect research that combined build solid foundations.
“I have described the likely reversal of the vicious circle with a multi-disciplinary protocol many times elsewhere on this site.”
Thanks for sharing your experiences! It is one of many very different ways some people get better. Some approaches seem to even contradict each other. There lies one of the main difficulties: if results were plain easy to copy then this disease would be no longer a problem.
That’s why I feel it is very important to keep notes, share experiences and details. The devil is often in the details. By having access to this information and having a group of “puzzlers” working on it I believe we can remove certain hurdles by sorting better out what could be the working principle of a treatment, what part of a treatment protocol does the actual heavy lifting, what part of the protocol is counterproductive, what prerequisites there are to success, what implicit details are important and how perceived contradictions can be removed…
That would in my opinion allow to have far better hit-to-miss ratios in trying to duplicate other patients successful results while avoiding pitfalls. As you and other mention it often takes multidisciplinary protocols to achieve good results. Now it already is hard to find one good approach. I feel knowing better how to chose and try different approaches is a near necessity for achieving good results by a multidisciplinary approach.
As there is a lot of distributed experience and knowledge among patients I believe this route is one of the more promising for the mid-term future. It would not provide a cure but being able to stabilize health or improve it significantly would be quite a meaningful result. It also would shed some additional light onto what to look deeper into for researchers.
It would help researchers a lot if there were some sort of database on the many different “expressions” of these diseases and the many different reactions to certain treatments/choices in relation to other relevant information. Now even the amount of people having FM/ME is a wild guess. Plenty of symptoms are hardly described let alone how many patients have them and how their disease varied in time…
Just had this discussion with my doc yesterday. He said “You’re not sleeping because your brain is on fire.”
I’m already doing LDN and boswellia, and we discussed several of the options on your list. We decided, though, to try high dose curcumin, which I’d used in the past with good results. Have you seen it discussed anywhere in this context?
Thanks!
I finally overcame my CFS after 23 years by focusing on this issue of inflammation in microglial cells. The inhibitors I take are oxytocin (lozenges), baicalein (a flavonoid from Chinese skullcap) and curcumin with black pepper (to maximize absorption). These resolved my symptoms to about 90-95%. The final nail in the coffin for CFS was when I added suma root. There has virtually been no research on suma root, but it is an Amazonian herb that the locals call “para tudo” which literally means “for everything”. There are a few random anecdotal stories on the internet of other people who have also stated that suma root cured their CFS. I also no longer drink any alcohol, or eat any sugar, and I eat very healthily (including not much red meat). I take melatonin for sleep. I never thought I’d see see the end of this, because CFS was a living nightmare, especially for the first 10 years. I feel like I have tried every drug and supplement on the market, and finally I worked it out. There is hope.
I looked up oxytocin to see what it would do for you. (Other than induce birth.) Found it could increase blood flow. It also has been found to help Autistic interactions and is a feel good hormone. It had pros and cons and was suggested making sure you know you’re low in it before taking as it could intensify some anxiety and undesirable personality changes for some. Not all autistic people were low in it. But those who were, it helped.
I use skullcap too. Has been a regular part of what I’m doing for months now.
Suma can be stimulating and it does help balance hormones.
Glad it’s working for you and you found your keys to success.
Issie
Thanks Issie. The protocol I take makes me feel very normal – i.e. not stimulated or sedated, just plain (but wonderfully) normal. I don’t think I even felt this well before I came down with CFS, which was triggered by what was diagnosed as a herpes-type retro virus. As I said above, I feel like I have tried everything on the market, and in some cases have had some horrendous side effects. For example LDN gave me nightmares, vitex gave me severe depression and Acetyl L-Carnitine gave me a horrific relapse. For me it seems balancing my hormones and fixing the neuroinflammation did the trick, and it was a long and expensive trial and error process. I could not have done it without the help of this website and a lot of additional research. The point is, it can be resolved. Best wishes to you my friend.
Excellent, Rebecca. People will only get better with multidisciplinary protocols. Don’t underestimate the contribution from the diet you are on. I would also bet you are getting exactly the right amount and intensity of exercise, even though you don’t mention this. Not too little (in which case your “condition” declines) or too much (in which case you have exhaustion relapses).
Hi Rebecca!
That’s some beautiful news! I am glad that you have found something working for you!
Do you think you could expand your protocol more? And your diet as well please?
Maybe you could email me or something, that would be very kind from you.
Thank you
Kind Regards,
Florin
Hi All,
For what it is worth, here is my protocol:
1. Oxytocin lozenges – 5 iu, BID. This inhibits inflammation in microglial cells and attenuates microglial activation. It also mediates your immune system.
2. Suma root – 1.1g BID. I buy this from a reputable on-line Australian (Perth) herbalist. This balances your hormones and mediates your immune system.
3. Baical Skullcap – 600mg BID. Again, I buy this from the same reputable herbalist. This also inhibits inflammation in microglial cells.
4. Hydroxy B12 lozenge. BID. In my view, this is the right B12 for CFS.
5. Multivitamin (no iron) – morning.
6. Omega 3 fish oil. 3000mg BID.
7. Magnesium malate – 1250mg TID.
8. Nicotine gum. Stimulates secretion of dopamine and norepinephrine.
9. Milk thistle – morning.
10. Lecithin – 1200mg – morning.
11. CoQ10 – 100mg BID.
12. Vit D3 – 5000mg – morning.
13. NAC – 600mg – morning.
14. Glycine – 1000mg – morning.
15. L-Tyrosine – 500mg – morning.
16. Turmeric – half a teaspoon BID plus a couple of whole black pepper corns for absorption.
For sleep I take 1mg of melatonin. If I can’t sleep, I take 12.5mg of Doxylamine succinate.
I have no alcohol or sugar whatsoever – this is important because of the inflammation they cause. I limit my fruit intake because of the sugar. My diet is largely the Mediterranean diet, i.e. lots of fresh vegetables, fish, chicken, nuts and olive oil. I eat “cheat meals” on the weekends (i.e pastas, pizzas, fish and chips). I can now drink coffee, when before it would exacerbate my symptoms. For exercise, I am limited to walking due to a back injury, but I no longer get post exertional fatigue.
In all, I was very lucky to have a doctor who was willing to try most of the medications recommended under the Dr Jay Goldstein protocol (some of which worked for while), but as it transpires what ultimately worked for me long term does not require prescriptions.
If I had only had limited funds, I would limit myself to the top 7 items above, plus the sleep products. The oxytocin lozenges can be purchased over the internet. Do not waste your time with the liquid version.
This took years of trial and error, and what works for me, might not for you. In my view, reducing neuroinflammation, and balancing your hormones and immune system are key.
Good luck my friends, never give up hope.
What is your source for the oxytocin lozenges ?
I buy my oxytocin from International antiaging systems (IAS). Sometimes I also purchase it from Peptides Clinic Australia when IAS runs out, but I’m pretty sure you need to be an Australian citizen to buy from the latter.
I didn’t mention it above, but milk thistle and omega 3 also inhibit inflammation in microglial cells.
Further,both hydroxy B12 and oxytocin scavenge nitric oxide which is released from activated glial cells during neuroinflammation.
Reducing the neuroinflammation from activated glial cells is the aim of the game, and is how I recovered.
Can you tell me more about how you use the nicotine gum and how it helps and if you had any side effects? Nicotine patch was recommended to try for my 15 year old but I’m hesitant because it seems like an odd choice.
Rebecca you are an outstanding researcher. I am a business owner who specializes in research and data analysis, who ran into a chronic centralized pain in my knees and my protocol looks very similar to yours after 3 years of consistent research & pain until recently. Can’t believe I found something so close. Seriously everybody with any disease that is related to neuroinflammtion (almost all chronic pain, CF, etc) try this protocol it’s really the only thing that is working right now. The one thing I’d add is HCG at 150 MG per day. You will need a prescription and it will require a few injections a week which you can do at your house. You can find it online (illegally) but I’d be cautious going this route. Way better to have a doctor monitoring everything and to have someone treating you that understands the importance of hormones & chronic pain. Most pain specialist in California know this now. Unfortunately outside of this area you won’t find any keeping up with the advances of the last few years.
Hcg play into balancing the hormones that are depleted from a chronic state which results in more pain. You should see a clinical difference within 48 hours. Dr. Forest Tennant believes it could even be doing some healing of the central nervous system. Who knows though… If you want to learn more about hormones and chronic pain search on google “HCG chronic pain dr forest Tennant.
Good luck to everyone & remember to get vocal as you figure out what works for you!
Good news on Bee Venom.
Hoshindo practitioner in Sedona is my new best friend. Am having good luck with bee propolis. It’s very calming. Hoshindo is new to me.
Found this article very interesting. I have ME/CFS, and have been a therapeutic cannabis patient since February. It has given me my life back! It helps with pain, fatigue and sleep! Different strains can be used to tailor to what you need on any given day. I haven’t been able to explain to anyone “why” cannabis has helped *me* so drastically. The glial cell explanation makes total sense now!
Cannabis has helped me a lot too. I’m going to dig into what’s going on further. 🙂