I sometimes fear that the 'state' of ME/CFS is analogous to logging all calls to the AA (the UK Automobile Association that provides a breakdown recovery service) involving cars not starting and grouping them all under 'failure to start syndrome'. Subsequently they are found to be due to no petrol; a wiring fault; faulty starter motor etc with no consistent findings and no association at all between the various faults. Alternatively it may be that there is one underlying systemic pathology that produces similar (but not always identical) symptoms regardless of the pattern of onset or eventual cause. I'm more confortable with the latter scenario.
Given the various onsets and the range of symptoms, one potential systemic avenue that I'm surprised hasn't been explored much to date is that of a sensory gating defect :
http://en.wikipedia.org/wiki/Sensory_gating
This is a fairly easy thing to test using a paired response paradigm to determine the degree to which the nervous system is able to habituate 'harmless' stimuli.
I'm aware that, in the past, Dr Goldstein has suggested sensory gating as the mechanism underlying ME/CFS but as far as I'm aware he hasn't published any experimental evidence to support this. I've only been able to find one dissertation that found a weak association between ME/CFS in adolescents and a sensory gating defect using an auditory stimulus :
http://docs.google.com/viewer?a=v&q...2-zqfV&sig=AHIEtbT6RtKcAUL1HEGgQFagTGz8pGlTkQ
On the other hand, there is a reasonably consistent literature around the role of a sensory gating deficit in Fibromyalgia. This study is interesting in that they found a significant difference between Fibro patients and controls using a painless somatic stimulus but not an auditory one :
http://docs.google.com/viewer?a=v&q...pE9pAE&sig=AHIEtbTvzqW_RVjFyK2BPmjQzQPZPk9frw
Of course, even if a sensory gating deficit is found in ME/CFS, the same question arises as it does in Fibromyalgia does the gating problem cause the condition or does it result from years of chronic illness?
Interesingly, Substance P (the pain related neurotransmitter/neuromodulator), which is sometimes found to be raised in ME/CFS which might be expected if pain signals are not properly attenuated, downregulates NK cell toxicity which of course might open up a route for opportunistic infections.
Additionally, it appears that norepinephrine provides the inhibitory signal that attenuates and thus habituates sensory input and if I recall correctly, Broderick's systems approach found that the adrenergic arm of the HPA axis is 'disassociated' in ME/CFS patients.
I'd be interested if anyone has come across any other similar studies in ME/CFS?