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What Causes Muscle Soreness & How To Reduce It

Delayed onset muscle soreness (DOMS) is a potential inhibitor of participation in, and frequency of, activity. DOMS is a diffuse muscle soreness occurring as a result of pressure, as well as active and passive movement, that occurs 24 to 48 hours after an exercise session. There are many beliefs about the causes of DOMS, and potential treatments. This month we review some of the things science knows, and does not know, about DOMS.

photoWhat causes DOMS

Delayed muscle soreness, as a result of exercise, has been blamed on everything from lactic acid, to muscle “micro-tears”, inflammation, and other “metabolic wastes”. While we know a great deal about what types of things may bring on DOMS, we still are not entirely clear on the cellular mechanisms at work.

Exercise that causes DOMS is usually described as sudden, novel, and unaccustomed activity. Eccentric exercise, muscle contractions occurring while a muscle is lengthening or stretching, is known to be one of the most reliable ways to induce DOMS.


Eccentric exercise grows muscle and makes you sore

A protein, called striated muscle activator of Rho signaling (STARS), is a muscle-specific signaling molecule in both heart and skeletal muscle. It is activated by calcineurin AND biomechanical stress. Eccentric exercise has much greater impact on these factors, calcineurin and muscle stress, then other types of activity. STARS is increased up to 10 times over baseline in eccentric exercise.

The above has implications for muscle soreness, soft tissue damage, and increased energy needed to recover, repair, and produce adaptation of the tissues over the days after exercise. Some suggest this has a role to play in obesity, as the extra energy required for these reactions shifts the body to build muscle and use fat (6-7).

A molecular mechanism for DOMS discovered?

A 2010 study out of The Journal of Neuroscience may have finally uncovered the molecular mechanism for muscle soreness in a mouse model of DOMS (1). Eccentric contractions were produced on anesthetized mice by using electrodes to contract the hind legs while at the same time moving the muscle into a stretched position.
Treatments to address. DOMS was then assessed with a pulsating electric pressure generator that essentially repeatedly thumped the muscle until withdrawal behavior was noted.

The researchers in this study analyzed the biochemical time course of the exercise modality. They singled out two compounds in particular, bradykinin and nerve growth factor (NGF). They found giving a bradykinin antagonist prior to exercise resulted in no DOMS compared to not giving the antagonist, which resulted in DOMS. However, bradykinin alone was not enough to cause DOMS. Only bradykinin with contraction and lengthening caused DOMS. Also, giving bradykinin antagonist after exercise did nothing to eliminate DOMS once it had occurred.

The rest of the story has to do with NGF. Post exercise NGF is elevated and is known to sensitize pain receptors. When an anti-NGF antibody was injected 2 days after exercise to reduce NGF, already present DOMS was reversed. Together this study showed that the combination of eccentric contractions along with bradykinin is needed to induce NGF which then seems to generate DOMS.

It is interesting to note that in this model of DOMS muscle injury was “minimal or almost absent”, and there was no inflammatory infiltration of macrophages/mast cells. This study also analyzed inflammatory compounds like IL-6 by using an IL-6 antibody in the same fashion as the NGF antibody. While other studies have shown IL-6 may have a sensitizing impact on DOMS along with other compounds, this study did not support that.

What works to help recover

In a detailed review of exercise induced soreness, Howatson et al. outlined the science behind what works and what does not (2). Disappointingly there is not much that does work. Some of the things that have been clinically fr sometime MAY not be as beneficial as we have thought. In this review cold and hot therapy provide only temporary help (in the case of cold) and little help, if any at all (in the case of heat) (2-4). Electrotherapies such as TENS ultrasound show potential promise, but have not yet been proven. NSAIDS, surprisingly provide little relief, and there is some evidence, they may even slow healing of soft tissues (9).

Massage, amino acid supplementation (prior to exercise), and most notably, more exercise seem to be the most beneficial treatments (2-4, 8). One interesting study, on using a cardiovascular burst between weight lifting sets, was shown to attenuate DOMS, compared to a group doing the same workout without the cardio bursts (5).

At the Metabolic Effect clinic we use a combination of nutrients to help the muscles recover quickly. Many of our clients swear by the results. The “cocktail” includes four different supplements: curcumin, bromelain, BCAA, and magnesium (supplements as pictured above).

Final Thoughts

DOMS is a significant inhibitor to participation in exercise. It is useful for the practicing physician to know what types of activities may induce DOMS and what types of treatments may benefit patients in recovery.





1) Murase, et al. Bradykinin and nerve growth factors play pivotal role in muscular mechanical hyperplasia after exercise (delayed-onset muscle soreness). The Journal of Neuroscience. 2010;30(10):3752-3761.

2) Howatson, et al. The prevention and treatment of exercise-induced muscle damage. Sports Medicine. 2008;38(6):483-503.

3) Lewis, et al. Muscle soreness and delayed-onset muscle soreness. Clinical Sports Medicine. 2012;31:255-262.

4) Symons, et al. Effects of deep heat as a preventative mechanism on delayed onset muscle soreness. Journal of Strength and Conditioning Research. 2004;18(1):155-161.

5) Davis, et al. Elimination of delayed onset muscle soreness by pre-resistance cardioacceleration before each set. The Journal of Strength and Conditioning Research. 2008;22(1):212-225.

6) Hackney, et al. Resting energy expenditure and delayed-onset muscle soreness after full-body resistance training with an eccentric concentration. 2007;22(5):1602-1609.

7) Eccentric exercise activates novel transcriptional regulation of hypertrophic signaling pathways not affected by hormone changes. 2010;5(5):e10695.

8) Sharp, et al. Amino acid supplements and recovery from high-intensity resistance training. The Journal of Strength and Conditioning Research. 2010;24(4):1125-1130.

9) Dahners, et al. Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft tissue healing. Journal of the American Academy of Orthopaedic Surgeons. 2004;12(3):139-143.