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 DOMS 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 delayed stage. This theory has been largely rejected, as concentric contractions which also produce lactic acid have been unable to cause DOMS. 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 DOMS, 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 DOMS, 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 delayed onset muscle soreness is a symptom associated with muscle damage, its magnitude does not necessarily reflect the magnitude of muscle damage. Soreness is one of the temporary changes caused in muscles by unaccustomed eccentric exercise. Other such changes include decreased muscle strength, reduced