The mechanism of<unk>  is not completely understood, but the pain is ultimately thought to be a result of microtrauma – mechanical damage at a very small scale – to the muscles being exercised.<unk>  was first described in 1902 by Theodore Hough, who concluded that this kind of<unk>  is "fundamentally the result of ruptures within the muscle". According to this "muscle damage" theory of<unk> , these ruptures are microscopic lesions at the Z-line of the muscle sarcomere. The<unk>  has been attributed to the increased tension force and muscle lengthening from eccentric exercise. This may cause the actin and myosin cross-bridges to separate prior to relaxation, ultimately causing greater tension on the remaining active motor units. This increases the risk of broadening, smearing, and damage to the sarcomere. When microtrauma occurs to these structures, nociceptors (pain receptors) within the muscle's connective tissues are stimulated and cause a sensation of pain. Another explanation for the pain associated with<unk>  is the "enzyme efflux" theory. Following microtrauma, calcium that is normally stored in the sarcoplasmic reticulum accumulates in the damaged muscles. Cellular respiration is inhibited and ATP needed to actively transport calcium back into the sarcoplasmic reticulum is also slowed. This accumulation of calcium may activate proteases and phospholipases which in turn break down and degenerate muscle protein. This causes inflammation, and in turn pain due to the accumulation of histamines, prostaglandins, and potassium. An earlier theory posited that<unk>  is connected to the build-up of lactic acid in the blood, which was thought to continue being produced following exercise. This build-up of lactic acid was thought to be a toxic metabolic waste product that caused the perception of pain at a<unk>  stage. This theory has been largely rejected, as concentric contractions which also produce lactic acid have been unable to cause<unk> . Additionally, lactic acid is known from multiple studies to return to normal levels within one hour of exercise, and therefore cannot cause the pain that occurs much later. A 2010 study on rats found that bradykinin plays a key role in the development of<unk> , using HOE 140, a bradykinin receptor B2 antagonist. Bradykinin is an inflammatory peptide released during exercise, and is involved in upregulating via B2 receptors nerve growth factor, which the study found served to maintain the pain by sensitizing muscular thin-fiber afferents, the majority of which were Group C nerve fibers. The development of muscular mechanical hyperalgesia was completely suppressed when administering HOE 140 into the extensor digitorum longus muscles of the rats' hindlimbs shortly before eccentric exercise, but was unaffected when the antagonist was given two days after. Bradykinin receptor B1 antagonists failed to suppress the hyperalgesia at all. Similarly, a dose of 10 μg of anti-NGF antibodies injected intramuscularly six hours after eccentric exercise prevented<unk> , but did not reverse it when given two days after. However, a triple dose reversed existing hyperalgesia by about 70% in three to four hours. Notably, injecting bradykinin into the EDL muscle alone and without concentric exercise did not induce hyperalgesia, suggesting that bradykinin is essential, yet not satisfactory, for NGF upregulation and persistent hyperalgesia after eccentric exercise. Relation to other effects Although<unk>  is a symptom associated with muscle damage, its magnitude does not necessarily reflect the magnitude of muscle damage.<unk>  is one of the temporary changes caused in muscles by unaccustomed eccentric exercise. Other such changes include decreased muscle strength, reduced range of motion, and muscle swelling. It has been shown, however, that these changes develop independently in time from one another and that the<unk>  is therefore not the cause of the reduction in muscle function. Possible function as a warning sign<unk>  might conceivably serve as a warning to reduce muscle activity to prevent injury or further injury. With<unk>  <unk>  caused by eccentric exercise (muscle lengthening), it was observed that light concentric exercise (muscle shortening) during<unk>  can cause initially more pain but was followed by a temporary alleviation of<unk>  with no adverse effects on muscle function or recovery being observed. Furthermore, eccentric exercise during<unk>  was found to not exacerbate muscle damage, nor did it have an adverse effect on recovery, indicating that<unk>  is not necessarily a warning sign to reduce the usage of the affected muscle. However, it was also observed that a second bout of eccentric exercise within one week of the initial exercise did lead to decreased muscle function immediately afterwards. Repeated-bout effect After performing an unaccustomed eccentric exercise and exhibiting severe<unk> , the muscle rapidly adapts to reduce further damage from the same exercise. This is called the "repeated-bout effect". As a result of this effect, not only is the<unk>  reduced the next time the exercise is performed, but other indicators of muscle damage, such as swelling, reduced strength and reduced range of motion, are also more quickly recovered from. The effect is mostly, but not wholly, specific to the exercised muscle; experiments have shown that some of the protective effect is also conferred on other muscles. The magnitude of the effect is subject to many variations, depending for instance on the time between bouts, the number and length of eccentric contractions and the exercise mode. It also varies between people and between indicators of muscle damage. Generally, though, the protective effect lasts for at least several weeks. It seems to gradually decrease as time between bouts increases, and is undetectable after about one year. The first bout does not need to be as intense as the subsequent bouts in order to confer at least some protection against<unk> . For instance, eccentric exercise performed at 40% of maximal strength has been shown to confer a protection of 20 to 60% from muscle damage incurred by a 100% strength exercise two to three weeks later. Also, the repeated-bout effect appears even after a relatively small number of contractions, possibly as few as two. In one study, a first bout of 10, 20 or 50 contractions provided equal protection for a second bout of 50 contractions three weeks later. The reason for the protective effect is not yet understood. A number of possible mechanisms, which may complement one another, have been proposed. These include neural adaptations (improved use and control of the muscle by the nervous system), mechanical adaptations (increased muscle stiffness or muscle support tissue), and cellular adaptations (adaptation to inflammatory response and increased protein synthesis, among others).
Delayed onset muscle soreness
Intractable pain
Chronic pain
Acute muscle soreness
Amplified musculoskeletal pain syndromes
Extrapyramidal symptoms
Heat intolerance
Acute visual loss