A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
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[theory]A portion of CFS sufferers have sensory gating / overstimulation issues

Discussion in 'General ME/CFS Discussion' started by Deltrus, Dec 20, 2015.

  1. Deltrus

    Deltrus Senior Member

    I'm sure many of you have heard that autism is primarily due to sensory gating issues and overactivity of excitatory components in the brain. I suggest that some forms of CFS are similar, but instead of being an issue of a mutation in the GABA pathway, it is an mutation that affects other cells as well, namely immune cells, increasing excitability.

    I suggest this is the case because I have terrible fatigue and other symptoms that are totally prevented by phenibut, a VDCC blocker. My constipation, my fatigue, my pain, are all fixed. My acne is cleared by the next day. My ringworm fungus on my chest disappears within a day. My intelligence and ability to get things done improves drastically.

    Before you say that phenibut is also a gaba b agonist, that is true, but baclofen is much more selective for gaba b and it doesn't have nearly as profound effects for me.

    The primary effect of VDCC blockers would be a reduction in intracellular calcium and a reduction in postsynaptic neurotransmitter release. (calcium fuels the process that makes neurotransmitter carrying vesicles dissolve). I should also add that an increase in calcium concentration makes a neuron more positive and more likely to send an action potential. (ie increases sensitivity)

    I have compulsivity, pain, anxiety(only when I'm hyper aware of people looking at / waiting for me), etc. And my body gets high amounts of sensitization, for example my leg twitches at the spot where my cell phone vibrates and I hear the noise in my head at the same time. All point to high excitatory activity and sensitization going on.

    When I take phenibut, or when I'm sleep deprived(and have coffee), and I play video games, I feel like I'm not actually looking at anything, and most of the information is subliminal while my main brain is thinking about things like "what is most important to do right now, what is dangerous etc". My performance goes way up despite feeling like I'm zoned out. Also I can listen to music while playing games without getting severe brainfog/fatigue within 15 minutes. It feels like there is a huge filter keeping the "stuff not involving conscious thought" below the stuff that "needs conscious thought".

    Every day I can also feel normal for the first hour of the day, but then my cognition just disappears. This is separate from activity level or diet. Perhaps the conscious brain eventually gets overwhelmed.

    Memantine does nothing for me so I assume that my problem doesn't involve NMDA receptors. Piracetam effects AMPA receptors and does nothing so I assume that doesn't have any relation to my fatigue either. I need strong antioxidants to function such as vitamin C, and otherwise my symptoms are all much worse. Although I don't need antioxidants when I take phenibut.

    There are many receptors that effect both neurons and microglia.


    (see table 1)

    From this article, I can see the candidates that could be the cause of my fatigue. They must increase intracellular calcium, and be in both neurons and microglia.

    The candidates are: mGluR1 and mGluR5a, Purinergic receptors: "Gi/Go-coupled P2Y (Y1, Y2, Y4 and Y12), P2X (X1, X4, and X7), P2Y8 and P2X6". And of course, VDCCs.

    The purinergic receptors are fairly new to me, this is interesting: https://en.wikipedia.org/wiki/Purinergic_receptor#Effects_on_chronic_pain
    Maybe the P2 receptors function in the same way for immune response, creating chronic immune responses and creating chronic states of heightened excitability of the immune system.

    Also VERY interesting, is that the P2Y receptors are activated by Uridine, and uridine supplementation for me gives extreme fatigue. Uridine is also found in beer.

    All in all, the mechanism I suggest is: Increased intracellular Ca+ in immune cells -> The cells are more sensitive to stimuli from pathogens/oxidation from exercise + the cells are more likely to trigger an inflammatory cascade. In addition, increased intracellular Ca+ in neurons -> disrupted sensory gating and sleep -> poor memory, fatigue, brain fog, poor focus.

    The cause of this mechanism of CFS could be genetic, or from gene expression changes due to viruses/the microbiome, or it could be self-perpetuating. Maybe a virus triggers these changes, so that the immune system is modulated in a certain way so that the virus is in a blind spot. For example, if the immune system is hyper sensitized to everything and has sensory gating issues, then it would get very confused and would be overwhelmed by information.

    Alright, that is all I got for now, too tired to write more.
    Last edited: Dec 21, 2015
  2. panckage

    panckage Senior Member

    Vancouver, BC
    Interesting... have you been using phenibut for long?
    The reason I ask is like many drugs (including phenibut) seems to work great for a while then but then tend to lose their effect over time
  3. Deltrus

    Deltrus Senior Member

    Yeah I don't use it more than once every 1.5 months. I use 2g at a time. I've been using it for 2 years. I don't want to risk making my problem worse, as phenibut tolerance happens fast.

    I'm interested in buying maybe some 300 mg pills and trying out low dose 2x a day, but that phenibut stuff is so acidic I would never put it in my mouth daily unencapsulated.

    And I've already tried fasoracetam for phenibut tolerance. I suggest people with CFS stay away from that stuff. It feels very neurotoxic to me. I got hot tingly sensations in all the nerves that normally give me pain, and it made them more inflamed. I also got what felt like seizures when I was falling asleep / waking up. Like, as soon as my mind started to lose consciousness, I would feel a bright light and my jaw clenching. And another side effect at doses of 50 mg was randomly feeling whole body "shocks" when I was tired which I think felt like it could have been from the autonomic nervous system doing weird shit. This last side effect lasted 1 week.

    So yeah don't try fasoracetam if you have a healthy nervous system. The effects of the drug itself were good, felt like piracetam without the compulsivity / mania. Afterwards, it gives a long lasting feeling similar to that of baclofen but without as many nice functional effects. Feels a bit like tiredness but isn't. It had a neutral effect on my neurochemistry. It feels like fasoracetam withdrawal has a bit of overlap with the effects phenibut/baclofen, just not the good parts.

    VDCC's are in most cells in the body so it is probably like using a shotgun to hit a squirrel, need something more selective with less damaging effects on the body. VDCCs are also a very sensitive system, perhaps there would be a less sensitive system. Ie. like angiotensin receptor II blockers for people with high blood pressure. Or maybe there is a negative feedback loop like there is with other receptors, where two receptors of the same type have opposite effects.

    Hopefully this area is researched more in the following years, both chronic pain and autism will probably do lots of related research. Right now people don't know what half these receptors do.
    Last edited: Dec 21, 2015
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  4. Sidereal

    Sidereal Senior Member

    Excellent post.

    It is only a subset, though, as you point out in the introduction. Jay Goldstein observed varying responses to such treatments decades ago, ranging from all symptoms going away to all symptoms getting worse and all kinds of outcomes in the middle. Recently there was a video by Alan Light posted around here somewhere showing clinical response and gene expression data (including purinergic receptors) after pregabalin and there was a subgroup that got better while the other group got worse.

    Personally, the approach you have outlined makes me vastly worse. Your observations re: immune alterations are very interesting. I've observed that calcium channel blockers (even supplemental Mg) make my dysautonomia and mast cell activation syndrome flare up terribly.
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  5. Deltrus

    Deltrus Senior Member



    I can't find the full study, but that is truly amazing. I was looking at exactly those two receptors, because they both increase intracellular Ca+ and increase inflammation. And yet the person who made that abstract analyzed the receptors and found candidates for CFS. He did the top-down approach while I did the bottom up approach.

    I also found a powerpoint that had a small study where some people with CFS responded well in the short term to lyrica/gabapentin, while others did not respond well.

    Interestingly, Caffeine is an antagonist to all P1 receptors. I never knew adenosine = purinergic receptor 1.

    I agree, that only some portion of people have this type of CFS.

    But the interesting thing, despite the pathology of my CFS being different (I don't hear many people raving about phenibut/gabapentin), my CFS symptoms are strikingly similar to everyone else's.

    - I don't get worse fatigue from short bursts of heavy exercise, only sustained light movements.

    - I have exercise, light, and heat induced chest rash/fatigue. If I experience all 3 together in medium amounts I get severe fatigue for a day or two. It only has to be a bit of sun / moving around to trigger it. Photosensitivity is a primary trait of lupus, but I've had extensive testing done and I don't have anything abnormal in any of the tests they have.

    - I've had 3 multiple multi-week bouts of extreme fatigue, and I've had pericarditis 4x.

    - I have full body tension, uncomfortable feelings, muscle/joint pain. I have poor posture that doesn't seem improvable through exercise or practice.

    - Poor memory

    - Drastically changing levels of cognition and fatigue throughout the day, in waves. I almost always get around 1 hour of great cognition after I wake up, followed by a drop that I can actually NOTICE. Like I am in a very advance train of thought, and then my train of thought just stops. And I get tired, brainfog. I can barely think at all after that, usually. Sometimes the crash is more gradual and less bad, depending on factors which I don't understand.

    - Gut problems, constipation, gas, uncomfortable bloating-like feeling.

    - Post meal fatigue

    - Very low baseline energy, very unrefreshing sleep, crashes throughout the day where I turn into a zombie state. My crashes are triggered by food, exercise, or even boredom.

    - Interestingly, just now I read that people with autism feel "painful" when they have to sit still without stimulus, and this is similar to me. I always thought I just had worse "boredom" than anyone else, because it feels unbelievably uncomfortable/unbearable to do things that don't attract my attention. It's like if you have a migraine it would encompass your entire attention, but instead it is a foggy dead tired feeling where you can only barely struggle to make sense of what you are hearing/doing.

    I always had to close my eyes and put my head down in class due to this sensation. I'd feel this "painful extreme tiredness" and just barely be able to will myself focus my attention on the teacher's voice so I could follow along in class. I'd feel so unbelievably tired, but would never fall asleep. I'd recover after class.

    Maybe I'm not actually experiencing boredom in the traditional sense, maybe my brain has poor sensory gating similar to autism, and without a very strong stimulus attracting my attention, my brain's focus and observations become completely chaotic, dysregulated, and overstimulated.

    All the above are temporarily 100% fixed by phenibut. Even my posture, memory, constipation(I take a huge dump). I'm probably just a small 5% subset of people with cfs so don't everyone go buy phenibut/gabapentin/lyrica.

    The boredom sensation and general tiredness I've had since like grade 2, but the CFS I've had since age 21, 2 years ago. The CFS started after my immune system was doing some crazy shit, that year I had pericarditis 2x, extreme post meal fatigue, one bout of 3 weeks extreme fatigue/depression where I was bedridden, and slowly during that year my fatigue started to mellow out and become more constant. My post meal fatigue slowly went away. Classical CFS symptoms appeared.

    Something very cool about phenibut, is that my memory starts to function differently. I can actually "feel" myself memorizing things. I repeat it to myself like 3x, feel the memory forming, and then I'd be confident that I would remember.

    EDIT: interesting wikipedia articles:

    Last edited: Dec 21, 2015
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  6. Battery Muncher

    Battery Muncher Senior Member

    Sounds really interesting, thank you for posting this. I'm going to try and read up more on sensory gating/ overload etc. over Christmas.

    It's interesting how many overlaps we have with Aspergers/ Autistic persons (regarding cognitive function)
  7. PatJ

    PatJ Forum Support Assistant

  8. PatJ

    PatJ Forum Support Assistant

    This used to happen to me. I finally, after many years, realized it was due to blood sugar drops. I found that I need to eat a small meal every 1 hour and 20 minutes to keep my blood sugar up and brain fog away. My blood sugar is fine during the night but I wake at 3:30 AM and need to eat by 4am or 4:15am.

    My best mental clarity is in the middle of the night when my blood sugar is stable. Unfortunately, I need to be trying to sleep at that time.

    If you try eating a small meal of slow digesting food (with protein, fat, complex carbs, and low/no sugar) when your cognition drops then you may find your mental abilities will recover within minutes. Avoid simple sugars that spike the blood sugar but then lead to a crash shortly after. I can't eat fruit at all because it's so quickly digested and high in sugar.

    I've had this for many years with CFS. I think it's due to low blood volume and/or low stomach acid (both in my case). Blood is redirected to the stomach for digestion. More blood is redirected for larger meals. Try eating a meal that is 1/4 (or smaller) the size of your regular meals to see if you have any fatigue after eating. In my case the small meals keep my blood sugar up, minimize or eliminate fatigue after eating, and I don't have the same drop in mental ability and blurry vision like I do when I eat a large meal.

    I also need to take Betaine HCL (with pepsin) tablets with any protein containing meal (even just a handful of nuts). Otherwise I get the same fatigue as when I eat a meal that is too large.
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  9. Deltrus

    Deltrus Senior Member

    I'l try the meal timing thing, even if it doesn't tie into my theory. I'l have to prepare some low glycemic index snack in bulk.

    I tried amisulpride and it did very little except give me insomnia.

    I don't really get post meal fatigue anymore, just that one year.

    Also another mechanism for why phenibut helps me so much might be through calming the vagus nerve's signal to the brain. Rather than a complete systemic receptor mutation/upregulation, it might be an isolated impairment of the vagus nerve due to viral infection and perhaps demyelination. HHV6 and other herpesviruses can demylinate, and without the myelin sheath, nerves would be much more exposed to the high amounts of extracellular calcium outside the cells.

    I've had pericarditis before and I occasionally get a similar heart pain, maybe it is the vagus nerve.

    Maybe the vagus nerve ties in with the sensory overload, where periods without a strong stimulus, or with too much peripheral stimulus, cause vagus "noise" to be relatively louder.

    It's also possible I have some sort of channelopathy. It could be not VDCC's but instead voltage-dependent potassium channels since two have related effects. VDCCs let positive calcium in when it wants to increase excitability, while VDPCs let positive potassium out when it wants to reduce excitability. Low VDPC activity would have a similar result to high VDCC activity. Channelopathy involving the vagus nerve could cause inflammation and symptoms similar to CFS,

    For example, I could have https://en.wikipedia.org/wiki/Neuromyotonia

    I have all of the symptoms. It actually says in wikipedia that it is a form of peripheral nerve hyperactivity, which is what I've been guessing.

    "muscle cramps, stiffness, myotonia-like symptoms (slow relaxation), associated walking difficulties, hyperhidrosis (excessive sweating), myokymia (quivering of a muscle), fasciculations (muscle twitching), fatigue, exercise intolerance, myoclonic jerks and other related symptoms."

    I actually almost certainly have https://en.wikipedia.org/wiki/Hemiparesis and pushings syndrome, my right side is weak and always lean to that side.

    There's a possibility of brain damage, since I HAVE fell and hit my head on the right side a few times when I was a kid, not sure if I got a concussion or something. Once was in the tub and once was when I was goofing around in a river stream. I showed symptoms at age 15, because after that age I always had messed up smiling muscles on my right side in school photos, I remember feeling guilty that my photo turned out weird.

    I've honestly just recently discovered I had weakness/paralysis on my right side, I have low awareness of those muscles so it just feels like twitching and pain.


    Morvan's syndrome seems like a very similar form of neuromyotonia, with which I share a few symptoms. I started experiencing "miliaria rubra" and itching around the same time my smiling muscle got messed up, around age 15.

    "Some of the muscles exhibiting twitching include the bilateral gastrocnemii, quadriceps femoris, biceps brachii, and right masseter." I get 4/4 of those, they are actually the only parts I can remember twitching, except my right foot rarely twitches. And my eye.

    Honestly, I seem to likely have Neuromyotonia + some symptoms of Morvan's syndrome, but only on one half of the body/brain. In addition, maybe I have excess vagus nerve irritation that is setting off my immune system.

    Altogether I am really happy. This is a new discovery which will lead to focused doctors appointments and a referral to a neurologist. I've never realized that my symptoms resemble the diseases on this corner of wikipedia. CFS was similar to my symptoms, but was missing out on "right side only symptoms", "fatigue when not very mentally engaged", "response to phenibut", "miliaria", "hyperhidrosis". I also don't get fatigue with short, heavy exercise, and I don't get a sore throat.

    Also I think that my atlas bone is always being pulled to the right due to muscle tension, I get a good feeling when I move the bone back into place, but it always quickly moves a bit to the right again. Before I learned how to move it to the left, it was really out of position and hurt quite a bit.

    There are probably quite a few typos here, but I had to work today and my cognition isn't that great. Maybe I'l fix it some time later.
    Last edited: Dec 23, 2015
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  10. Hip

    Hip Senior Member

    Very interesting post, Deltrus.

    Progesterone inhibits of voltage-gated calcium channels. Ref: 1 Might be something to experiment with. You can buy transdermal progesterone cream as a supplement without prescription. I sometimes apply around 10 mg of progesterone transdermal (which is around 500 mg of the cream) when I need to relax my brain.

    The antihistamine terfenadine inhibits calcium influx after activation of L-type voltage sensitive calcium channels. Ref: 1

    I tried phenibut myself, but with no noticeable effects (but the max dose I used was 500 mg).
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  11. Deltrus

    Deltrus Senior Member

    My last post I think I was too tired and didn't think properly. Neuromyotonia has much more serious muscular symptoms than what I have. It has CONSTANT muscle movement and bad cramping. I actually almost never get cramps. I got too excited when I saw morvan's syndrome also had symptoms of miliaria, even though miliaria is fairly common and anyone could have it.

    Many of the symptoms of channelopathies are very similar to CFS/Fibro.

    I probably just have a form of CFS, not some obscure and extremely rare (but treatable) disease.

    My first two posts were still good I think. Sensory overload and sensory gating is definitely an issue in some.

    Just goes to show that I should never post while tired because I wont notice things right in front of me.

    At least people can take away the lesson, just because the symptoms seem to match, you have to consider:

    1. How much the symptoms match other illnesses.

    2. The magnitude of each of the symptoms.

    3. What symptoms are actually common and might be unrelated to your disease? (ie miliaria)

    4. And lastly videos and pictures of patients with the disease is useful.

    Overall any type of theorycrafting is going to be largely useless compared to actual tests/research. I can't wait for that lipkin research and any other research coming up!
    Last edited: Dec 31, 2015
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  12. Thomas

    Thomas Senior Member

    Interesting post. I'll have to note that in my "to try list" as well as @Sidereal mention of pregabalin - although I had adverse reactions to even tiny doses of gabapentin - a Jay Goldstein favourite.

    By the way, my "to try list" is about as long as a full length mirror.

    I've been going through the Goldstein meds rather rapidly whenever energy permits me to obtain them in a desperate attempt to try and halt my progressive ME.
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  13. Marco

    Marco Grrrrrrr!

    Near Cognac, France
    Hi @Deltrus

    I'm pretty sure I fit into your sub-group. In fact I wrote a series of blogs based on the starting point that sensory gating issues may be a better pointer to what is wrong with us than 'fatigue' :

  14. ramakentesh

    ramakentesh Senior Member

    Really interesting post. Large meals generally lower blood pressure to a degree.
    My experience is quite similar to yours although weirdly I can feel better on central stimulants that also improve venoconstriction via alpha 1 receptors (Vyvanse, Psuedoephedrine) AND central Gaba meds like Klonopin or Phenibut. I feel they treat different aspects of the condition.
    My belief is in some there is abnormal activation of astrocytes in the brain that alter cerebral blood flow and neurovascular coupling and that this causes upregulation of glutamate as a response to impaired neurovascular coupling. Therefore a treatment protocol that improves venous return and venoconstriction peripherally and enhances gaba activity centrally might be the answer.
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  15. Hip

    Hip Senior Member


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