Muon's Case

[Muon]

Update: I have created some tables with data from July:
https://poiscenter.com/forums/index.php?topic=2545.msg32239#msg32239

[Muon]

House MD season 4 episode 11 'Frozen'. 31:00 in Dr. House tells his patient to go outside in the freezing cold for 5 min and see if she improves. If she improves it could be an indication for autoimmune disease (like SLE, vasculitis etc). This works for me. Does this mean my condition is autoimmune?

From page 2:

Did some googling and found this: Immune Responses to Exercising in a Cold Environment

''Even brief exposure to cold leads to increased levels of norepinephrine and cortisol, lymphocytosis, decreased lymphoproliferative responses, decreased levels of TH1 cytokines and salivary IgA, and increased lactate levels during exercise.''

Compare with the data from the previous post. The dysautonomia symptoms attenuate as well. Could mean there is an autoimmune origin to this. Autoantibodies involved in dysautonomia/POTS target adrenergic, angiotensin, muscarinic receptors or voltage-gated calcium channels, and in some cases, against nerve endings of small fibers. People with small fiber neuropathy are sensitive to carbs btw and do improve on low carb diets.

My hair is getting thin and my nails flexible at the moment.

[Muon]

Vibration excites something in my body. Something drops to the floor makes sound and it feels like it excites a cloud of particles in a domino's-like fashion, its net-momentum going one-way (it branches out as wel) only once, mostly in my lower torso (Most of the time it is traveling upward). It's like a wave.

Another scenario:
Glans penis (limp state and is not sexual related) becomes sensitive while walking or riding a bike that I have to stop walking for a few mins or stop riding the bicycle (I stop because the sensitivity increases with duration of movement up to the point that it hurts). The little friction it makes with my clothing seems to get amplified after repetitive motion. It gets better once I pause. (very mild tingling involved)

Also this:

Past Events

Januari 2020

A few times tingling sensation at the glans penis and became very sensitive to any friction (not sexual related just limp penis).

Februari 2020

I ate some liver and suddenly became feverish and nauseous for less than 30 sec of duration immediately after ingestion. Perhaps 5-10 mins after there were migratory colds traveling over my body and turned into systemic cold (shivering) after the migratory cold ended.

October 2020

Washing the glans penis during shower led to activation in lower back at the spinal area (which is already sensitive), no pain, just activation of something and it isn't muscle, no feeling of contraction. Activation stops when friction stops. Applying friction again flares up activity in my lower spine again.

Prolonged low grade stress gives me a burning sensation in a layer close to the skin (some locations that can be affected: back of neck, top of both forearms, sides of upper arms, shoulders, upper back). If I have to make a guess what is going on then I think it's CRH or another neutopeptide interacting with small fiber nerve endings or the nerve endings themselves releasing neuropeptides (Or again, MCs are reactive)

[Journey]

Washing the glans penis during shower led to activation in lower back at the spinal area (which is already sensitive), no pain, just activation of something and it isn't muscle, no feeling of contraction. Activation stops when friction stops. Applying friction again flares up activity in my lower spine again.

When I rub my glans/forehead exactly on the top area for example against the palm I feel this interesting kind of tingly kind of pulling feeling in the lower back area too either in nerves or something like that if I did that for many minutes it would feel way too intense and I would have to stop and once I do not rub anymore it just stops I already recall noticing that when I was a teenager.

[Muon]

Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability
IFN-g and IgG4 are MC activators. MCs may be activated at places of Th1 proliferation. What is the consequence of chronic activation? Markers related to microvascular endothelium may show abnormal levels. Bell's palsy might have been caused by an IFN-g spike which induced endothelin. IL-12, 15 and 18 are involved in th1 pol. What is the MC mediator profile for a combination of certain activators? Autoimmune MCA?

[Muon]

Tried a bit of a green smoothie containing pineapple and spinach, pineapple gives me diarrhea, spinach does other things. Haven't touch those ingredients for years.

I had to run to the toilet in ~ 1 hour after ingestion and had solid brown stool (yesterday's food) covered in green diarrhea. It was tolerable after ingestion until it hit a particular spot in my intestines. I won't touch that stuff anymore. Still highly sensitive to those ingredients especially pineapple. IBS.

[Muon]

The following scenario happened:

Starting to feel cold (drop in body temperature?). Usually once this happens I'm  cold for a while and cannot get warm. So what happened this time is that when I started to get colder something kicked in and  pushed the feeling of cold back. The response was late and not only that, it overshot the former equillibrium state, I started to sweat and gotten warm (sweating only happened at a few spots, asymmetric non-homogeneous behaviour). Then it decreased and dropped below that state...it oscillated a few times around that state before reaching it. This was easily observable since the process was slow in the order of tens of seconds. So the system that kicked in had quite some inertia that shouldn't suppose to be there in my opinion and could explain the oscillating behaviour.

So could this example be translated to the immune system? The immune response could be late (lag) and may need to be activated at time of orgasm to counter immunosuppression. Once orgasm hits it doesn't respond and one may fall into an immune compromised state. Then after a while when the immune system gets activated it may overshoot the normal state and will move into an overexcited state due to increased inertia and as a result gets stuck for a while there.

Now there might be two problems going on instead of one and biphasic treatment needs to be applied.
 
1) One needs to activate the immune system and time it with orgasm
2) Once immunosuppression is countered one needs to switch and apply immunosuppression to counter the late immune activation

Perhaps you can generalize this principle, in that, there is a lag of phase between input and output responses and the proportionality/ratio of the magnitude of response if off as well. 

Btw I also had the impression the low grade stress interfered with the scenario described at the top.

[Muon]

The Pyridostigmine isn't doing anything, it's like eating placebo. Here is what I took so far from top to bottom:

2 days: 1x30mg (10 mg tablets)
10 days: 2x30mg
2 days: 2x60mg
10 days: 3x60mg (60mg tablets)
5 or 6 days nothing, communication problem regarding med delivery
~10 days 3x60mg

[Muon]

Discovery of IgG4 Anti-Gliadin Autoantibody as a Potential Biomarker of Psoriasis Using an Autoantigen Array

"I have currently elevated IgG4 subclass and got a flare of my polyenthesitis"

https://en.wikipedia.org/wiki/Enthesitis
https://pubmed.ncbi.nlm.nih.gov/28387854/

[Muon]

Does norepinephrine modulate calcium currents in immune cells? How?

[Muon]

The dopaminergic system in autoimmune diseases

"In addition to the different stimulatory effects of DARs in T cell physiology, it is important to consider that each DAR displays different affinities for dopamine: DAR3 > DAR5 > DAR4 > DAR2 > DAR1 [Ki (nM) = 27, 228, 450, 1705, 2340, respectively] (49–51). Thus, low levels of dopamine, e.g., 50 nM, would stimulate mainly DAR3 in T cells, favoring Th1-like responses and T cell migration, whereas moderate dopamine levels, e.g., 300 nM, would stimulate DAR5 as well, inhibiting T cell function. It is likely that, by stimulating multiple DARs, higher dopamine levels promote complex effects in T cells, probably inhibiting T cell-mediated immunity (4)."

"Other pharmacological evidence indicates that selective stimulation of DAR2/DAR3 or selective inhibition of DAR1/DAR5 on DCs favors polarization of CD4+ T cell responses toward Th1, but impairs the Th17 fate."

I spent 4 months with colitis and lost half of my weight until thankfully my mother deduced that soy was the culprit. So I believe that, if it was a true allergy, I'd have had a more intense reaction. And yes, I've never tolerated soy well, and I've had that problem for as long as I can remember.

"Thus, specific IL-10 deletion of Foxp3+ Tregs results in spontaneous colitis, highlighting the fact that IL-10 produced by Tregs is instrumental in maintaining tolerance particularly at intestinal tissues"

"This protective role is most probably lost during colitis onset, since several lines of evidence indicate that dopamine levels decrease upon intestinal inflammation; and under these conditions, low dopamine levels may stimulate both the innate and adaptive compartments to produce highly inflammatory cytokines, favoring the development of colitis."

[Muon]

My brother's genetic profile:

COMT-V158M-Genotyp M/M
MAOA-Gen (30bp-VNTR) Low
BDNF Val66Met-Polymorphismus V/V
Serotonin-Transp.-Promoter PCR Genotyp K/L

Not sure if translated correctly:

"Overall assessment - neuroendocrine stress axis:

Based on the genotypes present, it is to be expected that catecholamines will be degraded with a delay both by COMT and by MAOA. Overall, therefore, catecholamine breakdown is slowed down significantly. This genetic constellation is associated with an increased release of the stress hormones cortisol and ACTH (Jabbi et al, Molecular Psychiatry 2007). With the patient's BDNF genotype, there is a risk factor independent of COMT, MAOA and proinflammatory cytokines for hyperactivity of the neuroendocrine stress-axis."

Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA

Does norepi decrease my IFN-g post O? If so then its suppression takes too long with other words catecholamine breakdown is slow.

"endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity"
The Sympathetic Nerve - An Integrative Interface between Two Supersystems: The Brain and the Immune System

I have had similar symptoms, where if I get incidentally aroused by something (which happens unfortunately often during abstinence), the arousal chemicals seem to be stuck in my brain for many hours afterwards. To your point this is not pleasurable at all and is frankly a gross feeling.  I haven't figured out any way to get rid of it other than waiting it out and trying to distract myself.

If I have a flare of arousal then I get the same impression of something that isn't cleaned up fast enough.

I had stress lately and got stuck in a stress state, I couldn't get out, trapped. Something in my calves spasmed slow and subtle during this scenario. This effect is a bit similar after I pass the point of no return but just before orgasm, the difference is that it then spasms more frequent and fast within a small timeframe, these are small areas, I don't get the impression they are muscle groups (perhaps muscle fibers or blood vessels).

CRH in major depression:
"Patients suffering from MD are known to exhibit hypersecretion of CRH, coupled with an elevated CRH concentration in the cerebrospinal fluid and a blunted ACTH response to exogenous CRH administration."

CRH can trigger mast cells --> VEGF.
SP from nerve endings can increase CRHR-1 on MCs leading to higher stress sensitivity.

[Muon]

https://forums.phoenixrising.me/threads/small-fibre-neuropathy-weirdness.81888/#post-2317661

"Sometexan84 did you ever have a skin biopsy done? That's how I learned about my small fiber neuropathy. The symptoms I have are pins and needles in my hands and feet, body aches, cold feet, frequent urination and a menthol cooling sensation on my skin. My autonomic nerve fibers are probably involved too because my hr sometimes becomes elevated upon standing."

Menthol cooling sensation... I could never find a word what is happening to my skin but this one fits better than a tingling/burning sensation. Small nerve fibers are perhaps getting inflamed, could also lead to dysautonomia.

Edit: Yep here we go POTS --> https://en.wikipedia.org/wiki/Small_fiber_peripheral_neuropathy

POISers who get symptoms from showers...could this be a sign of sensory small fiber neuropathy? Exercise intolerance?

https://www.healthline.com/health/small-fiber-neuropathy

[Muon]

My muscles easily tense up but it's difficult to get them relaxed once tense.

If triggers in general go over a certain threshold in terms of duration and/or intensity then the symptoms cannot be reversed for a while, the symptoms are living there own life so to speak, nothing you can do other than waiting out.

People with MCAD from mast cell forums can respond to orgasm. Symptoms I've seen are mainly allergic like symptoms, shorter onset (immediate to hours) and shorter duration (not more than a day) compared to ME/CFS. The CFS/ME people who respond to orgasm/ejaculation who I have seen so far seem to have a larger onset (12-24h) and duration (days), symptoms are mainly fatigue (exhaustion). I've seen only a handfull of people though. There are also some women on DINET, but can't remember their symptoms.

[Muon]

Histamine release in brain-->prolactin up--->dopamine down. Orgasm in males needs norepi driving dopamine further down. Low DA leads to an inflammatory immune profile.

Histamine-induced prolactin release: pharmacological characterization of receptors in male rats

[Muon]

Elevated B12. MMA could be measured.

Paradoxical Elevation of Both Serum B12 and Methylmalonic Acid Levels in Assessing B12 Status in Children With Short-Bowel Syndrome

NEITHER SERUM VITAMIN B12 NOR METHYLMALONIC ACID VALUES ARE RELIABLE MARKERS OF VITAMIN B12 SUFFICIENCY IN CHILDREN WITH SHORT BOWEL SYNDROME

Cytokines
Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome

[swell]

damn ... intriguing to read.  My skin is ultra sensitive to vibration, specially sense of touch, and specially the squeezing feeling.  I have purchased all kinds of massaging equipment, chairs, weighted blankets etc at home.  While my whole body is, but the torso area (also heart area) is most sensitive to touch.  Growing up I used to put mattress on top of me, since the heavy and squeezing feel on torso felt extremely comforting.  I also buy super soft clothes that feel soothing to skin. 

Vibration excites something in my body. Something drops to the floor makes sound and it feels like it excites a cloud of particles in a domino's-like fashion, its net-momentum going one-way (it branches out as wel) only once, mostly in my lower torso (Most of the time it is traveling upward). It's like a wave.

Another scenario:
Glans penis (limp state and is not sexual related) becomes sensitive while walking or riding a bike that I have to stop walking for a few mins or stop riding the bicycle (I stop because the sensitivity increases with duration of movement up to the point that it hurts). The little friction it makes with my clothing seems to get amplified after repetitive motion. It gets better once I pause. (very mild tingling involved)

"Many, if not most, of the symptoms related to neurosomatic disorders are caused by autonomic dysfunction which may be a result of inappropriate endothelin secretion. Blocking endothelin receptors may be an important way to treat neurosomatic disorders in the future"

"Both adenosine and gabapentin decrease pain in many patients with FMS by decreasing hyperactive neuronal activity. Gabapentin selectively opens K_ATP channels."

[Muon]

I have not Muon.  I only recently seen a doc, and they hesitantly did some blood tests, and wrote some negative comments on my medical records, for bringing a huge list to them, and the doc making me understand that you dont get tests because you are 'curious' to find.  I did get a heart echo-cardio though (by jumping through some hoops).
My cardiac fitness came excellent, 105% of Maximal heart rate.  I do have a incomplete right bundle branch block (that I think turns to complete when stressed) though doc says its all normal.  I would be curious if you have had echo cardio, or other folks can share their insights.

That said, my small fiber neuropathy, I think, is resolved now.

Swell, have you done any test for small fiber neuropathy yet?

I have cardiac problems since 2013 but never had an echo done. Demografx had a complete blockage if I'm not mistaken. I've asked for a SIBO test but never heard back. Same for biopsy of gut and stomach for mast cell count, also been ignored. Some volumetric spots on my body seems to have cleared up to some degree (less inflammation?) and POIS has attenuated a bit overal.

Sensitivity of my gut increased after ingestion of vegetable juice containing pineapple + period of stress. Woken up at night a few days in a row due to food passing through my gut (friction). It became more triggery to stress. I felt weak after a toilet visit (friction stool?). Had a flare of mild gut pain during the day that led to overal weakness and nausea for a brief moment. Drank 0,5 L water with salt plus a few drops of citric acid in the morning and everything came out an hour later as if nothing was absorbed. I'm stuck with all these triggers that affect local tissue in different ways. POIS is an extreme trigger.

Triggery spot in my gut lies at the center line and all the way at the bottom. I think it's the end part of the small intestines and problems begin from there (this location was triggered once during a summer by heat). Still problems with some sort of tension (muscle tone? Relaxation process?) that doesn't adapt properly to work/exercise. Recently, it was late in the evening and outside temperature was below freezing point, I could finally feel proper muscle pain after I had picked something up from the ground in my quadriceps which is normally absent.       

[Muon]

Hypoventilation, irregular breathing, pauzes in breathing--->preBötzinger Complex

Bad posture can give me slight irregular breathing rhythm--->Cervical instability--->brainstem compression

Complaints about a spot triggering in the middle of my head--->brainstem?

Opioid-induced respiratory depression: reversal by non-opioid drugs
Opioids depress breathing through two small brainstem sites
Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons

Ambient temperature/POIS are factors -->cytokines-->neuroinflammation/damage to neurons in the preBötzinger Complex? https://en.wikipedia.org/wiki/Pre-B%C3%B6tzinger_complex

Respiratory rate poll

[Muon]

Muon! If you haven't found this already you might be interested in this article as it seems to be related to your relatives at least if my theory holds true.
"All the females who got health problems felt better during their pregnancies and felt worse during their menstrual cycle."
AEA is low during pregnancy, but is high during menstruation, especially in the follicular phase.
The low levels in postmenopausal women and the high levels in the follicular phase suggest that steroid hormones primarily regulate AEA levels, with estradiol increasing the levels and progesterone suppressing them. The effect of progesterone could result from regulation of the degradation of peripheral AEA by peripheral blood mononuclear cells given that the levels of FAAH, the principal enzyme involved in AEA degradation, in these cells are regulated by progesterone. The induction of high AEA levels by estradiol could be mediated by its effect upon endothelial cells given that it has been reported that estradiol increases the release of AEA from these cells into the circulation.
https://academic.oup.com/jcem/article/89/11/5482/2844400?login=true

I had hCG on my radar but it seems to rise during menstruation cycle as well: https://pubmed.ncbi.nlm.nih.gov/19438167/
It may just be the absence of menstruation. My mother feels relatively better overal after menopause. She reacts to semen intravaginal, local burning sensation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570961/

Edit: Vandemolen had depleted IgM. Table 1 of the last paper shows that Glycodelin-A is able to lower IgM. I encountered this also in a paper about mu-opioids, in that, mu-opioids can decrease IgM.

I don't have a clue how immune cell counts fluctuate during pregnancy. I haven't looked into it.

What about neurotransmitter ratio's during pregnancy and how does these changes correlate with microbial changes during pregnancy?