Hi again Rich
I'm sure something like sensory gating may seem a little left field compared to mito/immune issues but I'll try to explain how I think it may be relevant.
Sensory gating basically refers to the mechanism by which we separate 'signal' from 'noise'. Our nervous system (I would tend to include the immune system in this) is constantly being bombarded by information from all the senses and its obviously a biological imperative to be able to separate out those signals that are important and suggest danger from those that are habitual and innocuous. Take the startle reflex. A sudden sharp noise will make you jump and your heart race. If the same noise continues with no associated danger then normally it becomes just more background noise and we become habituated to it. Similarly a sudden sharp pain might suggest an injury but you wouldn't want to be aware 24 hours a day that you are wearing a watch or that your shoes pinch a little. Normally these innocuous sensations are habituated and treated as unimportant background noise.
Problems come when there is a sensory processing deficit (which is a fairly easy thing to test experimentally using a paired response paradigm to determine the degree to which the nervous system is able to habituate 'harmless' stimuli).
In the past, a certain Dr Goldstein has suggested sensory gating as
the mechanism underlying ME/CFS. I'm not suggesting this as an alternative explanation to your own model but as an adjunct that might help explain some of our more bizarre symptoms. I have to admit to being frustrated sometimes by 'black box' explanations that a retrovirus or mitochondrial deficit can cause all of our physical and neurological symptoms without describing the mechanism. I suggesting that a sensory gating deficit may be such a mechanism.
I admit that I take a broad brush approach trying to reconcile various parts of the elephant so to speak. What struck me is that certain diseases/conditions where a sensory gating deficit has been shown (Schizophrenia; Altzheimers; bipolar disorder; fibromyalgia and of course autism) are ones where a glutathione deficit has also been shown. I'd suggest that there is very strong evidence that there is also a mitochondrial deficit in ME/CFS but that to date a sensory processing deficit hasn't been investigated beyond one small dissertation trial.
Of course a correlation between a sensory gating deficit and a glutathione deficit may be just that but there is evidence to suggest that they are causally linked.
For example experimentally induced damage to mitochondria alters the 'startle reflex' :
http://www.sciencedirect.com/science/article/pii/S0304394097004825
glutathione depletion can be shown to directly affect sensory gating in schizophrenia :
http://www.bioportfolio.com/resourc...Drug-Treatment-In-Prepulse-Inhibition-In.html
and glutathione supplementation can relieve some symptoms of schizophrenia :
http://www.ncbi.nlm.nih.gov/pubmed/18436195
Looking at how the sensory gating deficit manifests itself in these conditions is also suggestive. In autism there are the familiar problems of problems with sensory integration; overload phenomena etc. In schizophrenia, the inability to 'gate' sensory input leads to auditory and other hallucinations and of course in fibromyalgia you have the constant diffuse pain and fatigue.
Look then at our common symptoms : fatigue; pain; IBS; sensitivity to light and noise; feeling 'tired but wired'; food and chemical sensitivities. All could be easily explained if a sensory gating deficit means we are unable to screen out ongoing sensations. Some time ago I even initiated a thread of my clothes sensitivity that seemed to ring a bell with many members.
Its also easy to hypothesise that this constant bombardment of sensory input might overwhelm the nervous system resulting in brain fog; problems with multitasking; 'fatigue' and PEM.
I should add that I'm not suggesting that these sensations are 'illusory' or that we are just abnormally sensitive to pain for example. From my own experience, if I hit my thumb with a hammer it still hurts but no more than previously. On the other hand I can't sit still comfortably for any length of time as muscle and joint pain increases over time rather than habituating. I also don't rule out the possibility that a mitochondrial deficit may be causing for example leaky gut or microtrauma to muscles but that a sensory gating deficit would also accentuate the perception of it.
As I said, I tend to look at these things from a broad brush perspective as I don't have the biochemistry background and I can't explain exactly how a mitochondrial deficit and sensory processing deficit might be linked.
This blogger has had a go however :
http://bb-cfs.blogspot.com/2011/05/your-brain-on-atp-purinergic-signalling.html
it appears that ATP is the chemical messenger for the purinergic system (remember the Lights?) and this blog suggests that low ATP could result in a 'depression' of neural activity and hence brain fog etc.
I'd suggest that ATP also plays a key role in opening and closing the 'gates' that control sensory inputs in the purinergic system and that low ATP results in inadequate inhibition/habituation and thus a sensory gating deficit.
