The symptom signaling theory of ME/CFS involving neurons and their synapses

[Creekside]

Like I said earlier this was specifically in response to the idea that if a constantly active brain loop was causing ME/CFS, it hasn’t been detected so far because it is on the scale of a tiny cluster of neurons.

There's also the possibility that the abnormality isn't on the scale of a wire carrying high current vs no current; it could be a fairly subtle set of changes, with a high level of background signals. Furthermore, it's unlikely to be the exact same wiring pattern in the exact same place in all people.

I'm thinking of the pre-digital telephone system, where the cables consisted of a large number of individual wires woven together, connected in pairs through various switches for a given connection. I think you could get crosstalk between two conversations if the connections were in just the right--extremely unlikey but still possible--pattern. There would be no abnormality in the individual wires; it's the pattern as a whole responsible. Identifying the brain pattern responsible for ME's fatigue-like symptom might be impractical even after another hundred years of tech development. A huge hurricane might be caused by a specific butterly flap, but identifying which flap is not practical.

 

[Snow Leopard]

I don't like the trend towards people proposing non-testable hypotheses. We need something observable.

 

[Creekside]

We need something observable.

The problem is that ME's mechanism may not be observable with present technology.

 

[Utsikt]

The problem is that ME's mechanism may not be observable with present technology.

And it would be sufficient to be able to make testable predictions.

 

[Creekside]

And it would be sufficient to be able to make testable predictions.

True. For example, if the theory involved a small change in synapse function somewhere in the brain, a drug that alters brain-wide synapse function could test whether that affects the symptom severity. You would of course want to test safe drugs. What's a bit of safe hallucinating in the name of science?

 

[nataliezzz]

I know very little about the specifics of how all these drugs work. I think ideally you'd test with a drug that reduces neuron firing relatively globally in the nervous system since we wouldn't know what specific neurons or regions might be more important.

A person would do an intense exercise, and take the drug so that it is active throughout the exercise and for a long time after, maybe up until a crash would be expected. I'd probably expect that it would prevent the "wired" feeling, but that might not necessarily mean it's turning off the "problem" circuit. And then see if in the following days there is a crash.

Of course, there'd be the issue of it being difficult to do any kind of blinding when the drug is a strong nervous system depressant.

And take the following with a huge grain of salt since it's just one isolated anecdote, but when I search "gabapentin" on Phoenix Rising, the second result from a few days ago is someone saying that taking it before exertion helps. Unfortunately, quickly scanning through the hundreds of other results, I didn't notice others that discussed this.

Benzos are definitely helpful in this way for many ME/CFS patients. People take benzos before exertion/activity to prevent or reduce the severity of PEM and also to alleviate symptoms of PEM (& ME/CFS in general). My ME/CFS doctor said she has many patients who feel significantly better on a daily benzo (I could never personally recommend that to anyone due the risks of chronic/long-term use). See some of the comments under this post or search X/Twitter or r/CFS for benzos, Ativan, etc.

Clonazepam works this way for me, as does hydrocodone (also a CNS depressant) - now that I'm ~40% better in terms of fatigue/functional capacity than before I got on BiPAP, when I take hydrocodone I feel almost normal for several hours (maybe not normal normal [I don't think I remember what that actually feels like after 14 years of ME/CFS] - I couldn't go for a run e.g., but could probably go on a gentle bike ride, to a yoga class, etc. - I usually save it for house cleaning though). Whenever I've tried stimulants (nicotine patches, etc.) it gives me "fake energy" and though I feel like I can do more while on it I end up with PEM, whereas when I take clonazepam/hydrocodone it both reduces the fatigue/fatigability allowing me to do more and also helps to prevent/reduce ensuing PEM. Many ME/CFS patients report that dextromethorphan (which also has CNS depressant/sedative properties) works in a similar way (both to reduce severity of PEM when taken ahead of exertion as well as alleviating PEM when in it) - again search X or r/CFS for that. Benzos & DXM for PEM are both in the Bateman Horne clinical care guide.

 

[AliceLily]

Apart from the ME I often think the human body is geared to be too nervy? Or is life too busy, too much to do and we don't slow down enough and let some things go. My mother when she was alive would notice when I was walking too fast, she would say to me, 'slow down and walk in the grace of God'.