How does muscle damage lead to central nervous system fatigue?

Chris Beardsley
Jan 24 · 8 min read

Central nervous system fatigue is frequently discussed in the fitness industry. However, like many scientific topics, it is often misrepresented.

Many strength coaches think that central nervous system fatigue is something that happens to a greater extent after heavy deadlifts than after back squats (although it probably doesn’t). Few realize that central nervous system fatigue is a natural occurrence during every set of a workout, and is actually far more pronounced during and after aerobic exercise compared to during and after strength training.

Even so, muscle damage that is caused after certain types of exercise can trigger a large and sustained increase in central fatigue that lasts from one workout to the next, and this has very important implications for planning strength training programs, especially those that involve maximal eccentric contractions.


How is strength reduced immediately after a workout?

Immediately after a strength training workout, we experience a loss in the strength of the trained muscle. This reduction in strength is caused by three different factors: (1) peripheral fatigue, (2) central nervous system fatigue (central fatigue), and (3) muscle damage.


Peripheral fatigue involves three processes that are all fairly transitory in nature: (1) reduced release of calcium ions from the sarcoplasmic reticulum, (2) reduced sensitivity of the myofibrils to calcium ions, and (3) reduced force-producing ability of actin-myosin crossbridges. These processes cause either a failure in the activation of the muscle fiber, or a reduction in the force that the activated muscle fiber produces. Some involve the accumulation of metabolites inside the muscle fiber, while others do not.


Central fatigue is not the same thing as being tired, demotivated, or sore. It is not a whole-body feeling of tiredness. It is an effect that relates only to the control of the muscle that was trained, and it can happen regardless of how you might feel about working out. We define central fatigue as a reduction in our ability to exert voluntary force relative to our ability to exert involuntary force. It happens through decreases in motor unit recruitment, which means a reduction in the number of high-threshold motor units that are recruited, because of Henneman’s size principle.


Muscle damage can involve a very wide range of things, ranging from small disruptions to the sarcomeres, cytoskeleton, and cell membrane of the muscle fibers that were involved in the muscular contractions, to tears across the fiber and its surrounding collagen layer, to complete destruction of the muscle fiber and subsequent necrosis. Importantly, muscle damage occurs preferentially in the fast twitch muscle fibers that are controlled by high-threshold motor units, perhaps due to their less oxidative nature, or perhaps for other reasons that relate to their myosin heavy chain isoforms.


Each of these three factors can cause reductions in our ability to produce force with a muscle after a workout, but essentially there are only two mechanisms by which force production is reduced: (1) a decrease in the force that each muscle fiber can produce, and (2) a decrease in the number of muscle fibers that are activated by the recruitment of their motor units.


Does it matter if we do another workout before we have recovered?

Several studies have assessed the effects of doing a second workout 2–3 days after an initial, muscle-damaging workout. There seems to be no negative effect on the recovery of strength when a second workout is done soon after the first. We might interpret this to mean that we can train as often as we like, so long as muscle protein synthesis rates have returned to baseline.

However, while we may not cause any more muscle damage by performing a second workout for the same muscle a couple of days after a first workout, this does not mean that we will can stimulate a meaningful amount of muscle growth with that second workout.

Indeed, when many muscle-damaging workouts are done over a period of several weeks, the amount of hypertrophy that results is underwhelming, considering the amount of work that is done. This suggests that many of the workouts are actually not stimulating hypertrophy, despite subjects training with maximal effort.

Central fatigue can explain why this happens.

If we are still experiencing central fatigue when we train a muscle in a second workout, then we will not recruit all of the high-threshold motor units that control the muscle fibers that grow after strength training. This means that these muscle fibers will not experience any mechanical loading, and the second workout will not trigger them to grow. Since the highest-threshold motor units are the last to be recruited, and control the most muscle fibers, this is a very important point.


How does recovery occur after a workout?

The recovery of strength that occurs after a strength training workout occurs due to the dissipation of peripheral and central fatigues, as well as the repair of muscle damage.

When considered completely in isolation of one another, the dissipation of peripheral fatigue is very rapid after exercise, with effects lasting less than an hour. Similarly, the central fatigue that arises over the course of each set in a workout also recovers quickly (although when muscle damage is present, this changes). Muscle damage takes a varied length of time to repair, with very long periods of time being required when muscle fibers need to regenerate after necrosis. After normal heavy strength training, muscle damage is usually recovered after a couple of days. Yet, research has recorded signs that muscle damage repair can still be ongoing several weeks after a strenuous workout, when the muscle damage was extremely severe.

Even so, it is not really possible to consider peripheral fatigue, central fatigue, and muscle damage in isolation from one another, because they interact in at least two very important ways.

So how does muscle damage lead to central fatigue?


How does muscle damage lead to central fatigue?

Although it is logical that we should have evolved a protective mechanism that stops us from using a muscle too forcefully while it is damaged (either within the brain or within the spinal cord), the origin of this mechanism is unclear, and at least two explanations have been suggested.

Some researchers have suggested that muscle damage could lead to central fatigue through increased group III/IV afferent nerve signaling of pain from sore muscles.

Afferent nerves transmit information that is detected by sensory receptors in various parts of the body to the central nervous system. Afferent neurons are classified into groups according to their size, with group I being the largest and groups III and IV being the smallest. Group III and IV afferent nerves are linked to a range of sensory receptors that detect the mechanical loading of muscle fibers and of their metabolic environment, and are thought to transmit the sensation of delayed onset muscle soreness (DOMS) to the brain. Even so, afferent nerves can influence both spinal and supraspinal neurons, so it is feasible that such signaling could therefore cause central fatigue without affecting the size of the initial signal from the motor cortex.

The main challenge to this hypothesis is that the sensation of DOMS does not coincide well with the occurrence of central fatigue after muscle-damaging workouts. Central fatigue is greatest immediately after a muscle-damaging workout, and decays exponentially over subsequent days. In contrast, DOMS is minimal immediately after a workout, and increases to a peak over 24–48 hours afterwards, before gradually reducing again. Consequently, it seems unlikely that the pain of sore muscles causes the frequently observed reductions in voluntary activation after an eccentric training workout.

Other researchers have suggested that the inflammatory response that occurs after eccentric, muscle-damaging exercise could be responsible for the central fatigue that occurs after exercise.

A muscular inflammatory response could cause central fatigue either by (1) stimulating group III and IV afferent signaling at the spinal or supraspinal levels (as has been observed in animal models), or by (2) causing an increase in the levels of inflammatory cytokines in the brain, which is also known to cause sustained fatigue after exercise in animal models.

These hypotheses are attractive, because the time course of the inflammatory response to eccentric exercise is similar to the time course of central fatigue, which is usually greatest in the hours immediately after a workout and decays over a couple of days afterwards (although it can last for over a week, when muscle damage is severe). Similarly, leukocyte (white blood cell) infiltration occurs within hours of an exercise bout, and is related to the losses in muscle force but not to the sensations of muscle soreness. The earliest leukocytes to arrive are neutrophils, and can be observed inside the muscle for the first 24 hours after exercise. Later, macrophages arrive, and their presence can be recorded for 2–7 days after exercise. Cytokines also cause responses that can be observed within the first 24 hours after a workout. Even so, it is very unclear whether any specific element of the inflammatory response can be linked to the presence of central fatigue at this stage.


What is the takeaway?

Central fatigue is a very important consideration during strength training for hypertrophy. If a workout is performed when central fatigue is still present from a previous workout, many of the high-threshold motor units will not be recruited (even when training to muscular failure), which means that they will not experience any mechanical loading, and will not grow.

The central fatigue that occurs after strength training workouts is likely caused by muscle damage. It seems to arise due to the inflammatory response that occurs in the first few hours after the workout, but the exact mechanisms and signaling processes are still unclear.

Chris Beardsley

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