ME/CFS as a biological information processing problem

Indeed.

I was unwrapping the lovely green paper from a bar of Green & Black's organic smooth mint this afternoon & thinking perhaps it should be renamed 'hypothalmic blend'. I reckon their corporate owner Mondelez would be the perfect backer for a Wellness offering. I mean all it needs is a name right? It can be as empty of nutrients as you like

 

I have probably mentioned that in the early years I day dreamed that I would be famous for discovering that parsnip juice put RA into remission. I never thought that it was just the parsnip juice that was going to turn out wrong.

Eating lettuce whole while sitting in an ice tub might just about put ME/CFS into remission, but I think there might be a better suggestion in due course.

 

Wait--you mean it doesn't???

 

Using the term remission is quite specific though.

What about all the drinkers who have prevented themselves from ever getting it?

does the type of lettuce matter? I’m guessing certain types are harder to get hold of year-round.

 

Definitely cos icicle.

 

It’s well known that pasties cure all and my hypothalamus definitely has a clock which measures how long since I’ve had one. Or maybe it’s just the swede…

 

That interferon/ISG-expression could make PWME feel lousy must lead somewhere, surely? Itaconate-driven peroxiredoxin5-inhibition could surely trigger ISGs yet leave interferon undetectable? Apologies but the concrete reality of "feeling lousy" keeps tapping away at the window.

 

Yes, at some point the signal reaches neurons in the parts of the brain that 'feel' things. The receptors for interferon might be specialised hypothalamic cells or, as discussed on another thread, more peripheral nociceptors. Lousiness is ultimately a reflection of some pattern of electrical potentials in one or more cells that supports a conscious experience of how we feel. It is not going to be encoded chemically. So there is no need for the bit of the brain that feels the lousiness to itself be lousy. In general the understanding in neurobiology is that events within brain itself do not feel like anything much, other than what their electrical patterns portray of what is going on somewhere else.

'Concrete reality' is always known to us as a representation in 'brain-ese'.

 

So, Jonathan… does this theory incorporate your ideas about consciousness that you have posted on Qeios?

to be clear, here is the reference…

https://www.qeios.com/read/DEUK7V.3

 

Not specifically, although the same logic is applied. The idea that all our perceptions and conceptions are painted in electrical potentials is pretty standard dogma at least since Marr in the 1970s. My own ideas relate to exactly where those signals are 'manifest' to 'me'. But they are extra.

 

So you saying that the "feeling lousy" is only encoded in the electric potentials, if so, will the "feeling lousy" be measurable or do we need to look elsewhere to measure?.

 

One day we might be able to measure the patterns in brain cells that code for feeling lousy. It is likely to be easier to measure the signals as they being sent in rather than as they are received. We probably already know that certain signals in thalamus or limbic system are likely to encode feeling lousy. But it is hard to be sure, that they are directly responsible for the feeling. They might encode thoughts about the fact that one has felt lousy and so on.

 

Well, how would we know for sure without doing at least several dozen pragmatic trials?! More research is always needed!!

 

Putting the p value in parsnips?

 

Someone else mentioned FcγRI can be expressed on neuronal and endothelial cells. Given discussion about problems there, this seems potentially interesting. How could it tie in. More speculation….

If FcγRI is expressed, even in low numbers, on neurons (particularly dorsal root ganglia) this could help explain some of what is discussed here.

If for instance, the calcium balance was modified in even parts of the cells, this could change how the nerve behaves, shifting resting potential. We could see both changes in some more easily firing (hypersensitivity) and some the reverse (less responsive).

We don’t need to say inhibitory or excitatory, we can have both, it depends on the nerve and in particular the dendrites or axon terminals affected, these need be only small localised changes but they could shift the overall electrical balance in significant but also importantly, temporary, ways.

Below are various papers, I’m going to pretend to have read them all, but I have skimmed bits and they may back some of his up and/or give others some interesting reading. It could all be wide of the mark and at best there are bits missing but there seems to be at least speculation about these topics.

Spoiler

“Moreover, IgG-IC can directly activate neuronal FcγRI producing an increase in intracellular calcium ([Ca2+]i”
Nociceptive neuronal Fc-gamma receptor I is involved in IgG immune complex induced pain in the rat
https://www.sciencedirect.com/science/article/abs/pii/S0889159117300636

Neuronal Fc-gamma receptor I mediated excitatory effects of IgG immune complex on rat dorsal root ganglion neurons
https://www.sciencedirect.com/science/article/abs/pii/S0889159111001267

Neuronal FcγRI mediates acute and chronic joint pain
https://www.jci.org/articles/view/128010

Detection of Fcγ receptors on human endothelial cells stimulated with cytokines tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)
https://academic.oup.com/cei/article-abstract/112/3/533/6480526?redirectedFrom=fulltext

Involvement of Fc Receptors in Disorders of the Central Nervous System
https://link.springer.com/article/10.1007/s12017-009-8099-5

Expression of Fc epsilon receptor I on primary sensory neurons in mice
https://journals.lww.com/neurorepor...on_of_Fc_epsilon_receptor_I_on_primary.7.aspx

Sensory Neuron Expressed FcγRI Mediates Postinflammatory Arthritis Pain in Female Mice
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.889286/full

Fcγ Receptor I–Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis
https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.41386

Neuronal C‐Reactive Protein/FcγRI Positive Feedback Proinflammatory Signaling Contributes to Nerve Injury Induced Neuropathic Pain
https://pmc.ncbi.nlm.nih.gov/articles/PMC10074098/

 

(Edit, I probably posted these two in the wrong order, oh well, a disadvantage of drafting thoughts in notes over time, but the suspect analogy came first)

I think it was Jonathan who asked why these cells would have receptors for interferon gamma? I wondered if it was perhaps it’s a form of protection.

The central nervous system has the blood brain barrier but what about the peripheral? I believe there are other systems here but I haven’t learnt about them yet so here we go

My suspect analogy here is… If I was a peripheral nerve cell doing business, I’d want to be really ‘efficient’, maybe cut a few corners in the good times and be lax on security, let lots in and out with minimal fuss. But, if I caught wind of something dodgy in the vicinity I’d probably be a lot more careful, possibly to the detriment of that efficiency and primary function, just to be on the safe side.

Maybe I’d have my own security system and bouncers, not entirely rely on the local police. And if I had to stop punters coming in for a bit but it saved me from getting smashed tables and chairs and a big cleaning bill, maybe that would be okay.

So these nerves may have some receptors like FcγRI or other, and when they get triggered, he cell becomes less permeable or more defensive in a way, puts the guardrails up a notch.

Maybe this is why we feel tired when ill, parts of our peripheral nervous system are deliberately becoming less efficient for self protection, both at a cellular level and also if we rest we’re unlikely to do ourselves more damage, so maybe more likely to recover. An adaptive advantage?