Muscle soreness after exercise has nothing to do with lactic acid

The muscle soreness that appears after exercise has a more formal name: delayed onset muscle soreness (DOMS). A widely circulated belief claims that post-exercise muscle pain is caused by the accumulation of lactic acid within muscle tissue. In reality, this explanation was rejected by scientific research long ago. Nevertheless, the idea has continued to circulate through popular discussions, and many people still accept it today.

During exercise, when muscle cells repeatedly contract, they release a variety of substances, including lactate, bradykinin, inflammatory mediators such as TNF-α, IL-6, and IL-1β, as well as several neurotrophins.

Lactate is indeed produced during muscular activity, but it is rapidly transported through the bloodstream to the liver, where it is metabolized. Because of this rapid removal, lactate does not remain in muscle tissue long enough to account for the soreness that appears hours or days later.

Cori Cycle（Image source：PRESSBOOKS， CC BY 4.0 ）

At present, the precise cause of DOMS has not been fully resolved. Three main possibilities are commonly discussed:

1. Inflammatory responses

2. Damage to muscle fibers

3. Increased sensitivity of pain-sensing nerves

Research conducted by the Japanese physiologist Kazue Mizumura suggests that the first two explanations may not be the primary cause of muscle soreness. In experiments using mice, the muscles that developed DOMS did not show large infiltration of immune cells, and soreness could still occur even when muscle fibers showed no detectable structural damage. These observations indicate that inflammation and structural injury alone cannot fully explain the phenomenon. Instead, the findings point toward heightened sensitivity of pain-sensing nerve fibers as the key factor.

The proposed mechanism is as follows. During exercise, bradykinin produced within the muscle stimulates the production of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). These molecules act on sensory nerve fibers within the muscle and lower the activation threshold of Aδ and C fibers, which are responsible for transmitting pain signals. When their sensitivity increases, the muscle becomes more responsive to mechanical stimulation, producing a condition known as mechanical hyperalgesia. This heightened pain sensitivity is now considered one of the most plausible explanations for delayed onset muscle soreness.

Although many details remain to be clarified, recent physiological studies increasingly support the idea that DOMS arises primarily from changes in sensory nerve function rather than from lactic acid accumulation.

The pathway causing muscle soreness（Image source：Kazue Mizumura & Toru Taguchi， CC BY 4.0 ）

（Additional information）

Why do muscles produce lactate during exercise?

Lactate production occurs because muscle cells require large amounts of energy in a short period of time. To meet this demand, they accelerate the glycolytic breakdown of glucose, generating ATP and NADH.

When glycolysis proceeds at a very high rate, the downstream aerobic respiration pathway—particularly the electron transport chain—cannot process all of the generated NADH because oxygen availability becomes limiting. As a result, pyruvate, the final product of glycolysis, accumulates.

At this point, the enzyme lactate dehydrogenase converts pyruvate into lactate. During this reaction, NADH is simultaneously converted back into NAD⁺. The regeneration of NAD⁺ is essential because glycolysis requires it to continue operating. Without this recycling step, excess NADH would halt glycolysis and energy production.

This metabolic pathway is known as lactate fermentation. When lactate later reaches the liver through the bloodstream, lactate dehydrogenase converts it back into pyruvate, producing NADH in the process.

Glycolysis and lactic acid fermentation（Image source：Grace RF et al， CC BY-NC 4.0 ）

Author: Shui-Ye You

Reference:

Kazue Mizumura & Toru Taguchi. (2024). Neurochemical mechanism of muscular pain: Insight from the study on delayed onset muscle soreness. J Physiol Sci.