Sim,
Your points are well made. To my knowledge no one has yet found the single biochemical factor that "causes" the sensations of fatigue. On the other hand there is now certainty that the most important determinant of the extent to which fatigue is sensed during exercise is how close you are to the finish of the event. Let me explain (please excuse if you already know this information).
In 1960 the Swedish scientist Gunnar Borg wondered if humans could describe in simple terms how hard they perceived the exercise to be. He found they could and developed the Borg Scale for the Rating of Perceived Exertion (RPE). Borg was interested only in how this scale related to the intensity of the exercise; he had little interest in how the RPE might change as the exercise became more prolonged. Yet in 1976 he published a paper showing that in people doing a VO2max test, the RPE rose as a linear function of the exercise duration. Thus he reported that the rate at which the RPE rose could be used to predict for how long they would be able to exercise (given that each individual stops at a maximal RPE, the exact value of which is specific to the individual). But he took this aspect of his research no further.
I rediscovered this finding in 2004 when I looked at some data from my Australian colleagues who measured the RPE during two bouts of prolonged exercise at a fixed work rate, one when the subjects were carbohydrate-loaded and one when they were carbohydrate depleted. The first interesting finding was that the RPE rose as a linear function of the exercise duration even from the first measurement made during exercise. The increase continued in this linear manner until the athlete reached his or her maximal RPE at which time he or she would terminate the exercise bout.
The immediate implication of this finding was that if you knew the maximal RPE that the athlete could achieve, by plotting the rising RPE against exercise time, you could predict from quite early on during the exercise bout the exact time at which each subject would terminate the exercise bout.
Next we showed that when the data were normalized to 100% of the exercise time, the rate at which the RPE rose was identical for both exercise conditions, indicating that this finding is a biological "law".
The point of course is that if the RPE rises as a linear function of the exercise duration beginning from the beginning of exercise, then it is set "in anticipation", it is not likely responding purely to biochemical changes in the body (as more likely the mechanism according to the Hill model) and is more easily explained as the mechanism by which something like a proposed CG would be able to insure that the exercise terminates before damage occurs.
Since then a number of scientists, not all of whom are sympathetic to the CG model, have confirmed that these findings apply also to competitive sport in which athletes compete at their own chosen paces and in which, again, the RPE rises as a linear function of the exercise duration. Thus again the athletes performance time could be predicted by knowing how quickly the RPE was rising early on during exercise. We have since shown in a paper accepted for publication a few weeks ago, that the RPE rises as a linear function of the exercise duration which we manipulated in the laboratory by having the subjects exercise at different intensities in different environmental conditions. Always the rate at which the RPE rose predicted the exercise duration.
This finding might have some interesting practical applications. For example if you were to know how quickly your RPE was rising during competition, you would know quite early on in the exercise bout what your finishing time was likely to be. At present the data we have are for exercise up to 21 km (13 mile) and not further. Thus we do not know whether this finding applies for more prolonged exercise as in marathon or ultra marathons.
Here is an interesting observation: If you are training an athlete whose maximum RPE is 19 units and if he is doing an interval session and if his RPE at the end of the first 3 intervals in 14, 15 and 16, then his brain clearly believes that he is only doing 6 intervals (ie progressive RPE's of 14,15,16,17,18,19). Usually this is because he was told at the start that he was doing only 6 intervals. If he did not know how many intervals he was going to be asked to do, how did his brain settle on 6? Did he "know" the coach so well that he knew before he began that the coach would expect him to do only 6 intervals?