with leaden, sore muscles, at which point most of us slow or stop exercising. Rarely, if ever, do we push on to the point of total physical collapse.

But scientists have long been puzzled about just how muscles know that they’re about to run out of steam and need to convey that message to the brain, which has the job of actually telling the body that now would be a good time to drop off the pace and seek out a bench.

So, a few years ago, scientists at the University of Utah began studying nerve cells isolated from mouse muscle tissue. Other research had established that contracting muscles release a number of substances, including lactate, certain acids and adenosine triphosphate, or ATP, a chemical involved in the creation of energy. The levels of each of those substances were shown to rise substantially when muscles were working hard.

When they exposed the mouse cells to a combination of all three substances, many of the nerve cells responded. In living muscle tissue, these neurons presumably would send messages to the brain alerting it to growing muscular distress. Interestingly, the scientists found that different neurons responded differently, depending on how much of the combined substances was added.

Eventually, the scientists next decided to repeat and expand the experiment in humans. For a study published in February, they recruited the thumbs of 10 adult men and women. Their thumbs were needed since the researchers wanted to study muscles that were accessible and easily held still. The researchers injected lactate, ATP or the various acids just beneath the tissue covering one of the thumb muscles. After the discomfort from the injection had faded, they asked the volunteers if they felt anything. None did. They then injected volunteers’ thumbs with the three substances combined and at a level comparable to the amounts produced naturally during moderate exercise. After a few minutes, the volunteers began to report sensations similar to fatigue, although the thumbs had not been exercised at all.

In a subsequent injection, the researchers increased the amount of the combined substances until they approximated those produced during strenuous exercise. The volunteers reported intensified sensations of muscular fatigue and also some glimmerings of aching and pain.

Finally, the researchers upped the levels of the substances until they were similar to what is seen during all-out, exhausting muscular contractions. After this injection, the volunteers reported considerable soreness in their thumbs.

What the study’s findings indicate, said Alan R Light, senior author, is that the feeling of fatigue in our muscles during exercise probably begins when these substances start to build up. Small amounts of the combined substances stimulate specific nerve cells in the muscles that, through complicated interactions with the brain, cause the first feelings of tiredness and heaviness in our working muscles.

These feelings bear only a slight relationship to the remaining fuel and energy in our muscles. They don’t indicate that the muscle is about to be forced to stop working. But they are an early physiological warning system, a way for the body to recognise that up ahead lies a limit.

Each subsequent increase in the levels of lactate and other substances amplifies the sense of fatigue, Dr Light said, until the substances become so concentrated that they apparently activate a different set of neurons, related to feelings of pain. At that point, the exercise starts to hurt and most of us sensibly will quit, staving off muscle damage should we continue.

Of course, improvements in physical performance sometimes demand that we continue through fatigue and on to achiness. “There is some truth” to the adage about “no pain, no gain,” Dr Light said. But disregarding all the signals from your muscles can be misguided, he said.

—©2014 The New York Times