Initial events in exercise-induced muscular injury
Abstract
Immediately following unaccustomed exercise, particularly that with eccentric contractions, there is evidence of injury to skeletal muscle fibers: a) disruption of the normal myofilament structures in some sarcomeres, observable with both light and electron microscope and b) loss of intramuscular proteins (e.g., creatine kinase enzymes) into the plasma, indicating damage to sarcolemma. This pathology is probably responsible for the temporary reductions in muscle force and delayed-onset soreness that can occur following eccentric exercise. The mechanisms underlying this injury are not known, although loss of intracellular Ca2+ homeostasis could play a primary role. In other experimental muscle injury models, elevated [Ca2+]i appears to cause release of muscle enzymes through activation of phospholipase A2, which in turn could induce injury to sarcolemma through production of leukotrienes and prostaglandins, through free O2 radical formation (in the subsequent lipoxygenase and cyclooxygenase reactions), and/or through release of detergent lysophospholipids. On the other hand, the mechanism responsible for the rapid damage to myofibrils caused by increased [Ca2+]i is unknown. Regardless of the cause(s), the initial and early events in the injury process are autogenetic; i.e., they are indigenous to the muscle cells and occur before phagocytic cells enter the injury site.
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If repeated multiple times, eccentric contractions are a useful tool to induce a physiologically-relevant injury to skeletal muscle, resulting in damage to the contractile apparatus and loss of function.
“If repeated multiple times, eccentric contractions are a useful tool to induce a physiologically-relevant injury to skeletal muscle, resulting in damage to the contractile apparatus and loss of function (2, 3).”
From Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice (2021) · cites this paper as [2]
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“Majority of researchers believe that strength reduction is because of myofibrillar damage involving Z-band and sarcomere disruption caused by performing eccentric contractions [1-3, 37,38].”
BackgroundMattacola, C. G., Perrin, D. H., Gansneder, B. M., Allen, J. D., & Mickey, C. A. (1997) · Journal of Sport Rehabilitation · doi:10.1123/jsr.6.1.38 · Cited by 78 · see citing works
“Delayed onset muscle soreness is characterized by pain, loss of range of motion and strength, and edema (1, 3, 4, 21).”
BackgroundElectro-membrane microcurrent therapy reduces signs and symptoms of muscle damage
Lambert, M., MARCUS, P., Burgess, T. L., & Noakes, T. D. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200204000-00007 · Cited by 86 · see citing works
Dousset, E., Avela, J., Ishikawa, M., Kallio, J., Kuitunen, S., Kyröläinen, H., Linnamo, V., & Komi, P. V. (2007) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31802dd74e · Cited by 78 · see citing works
“Armstrong (1) has defined four stages of muscle damage processes and subsequent recovery.”
BackgroundInfluentialEffects of Running Distance and Training on Ca2+ Content and Damage in Human Muscle
Overgaard, K., Fredsted, A., HYLDAL, A., Ingemann-Hansen, T., Gissel, H., & Clausen, T. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000126468.65714.60 · Cited by 76 · see citing works
Influence of Compression Garments on Recovery After Marathon Running
Hill, J., Howatson, G., van Someren, K. A., Walshe, I. H., & Pedlar, C. R. (2014) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000000469 · Cited by 74 · see citing works
“E xercise-induced muscle damage (EIMD) often occurs after strenuous physical activity, particularly when the exercise has an eccentric component or is of a prolonged duration, both of these characteristics are typical of long-distance running (7,29).”
BackgroundDoes Upper Airway Muscle Injury Trigger a Vicious Cycle in Obstructive Sleep Apnea? A Hypothesis
Petrof, B. J., Hendricks, J. C., & Pack, A. I. (1996) · SLEEP · doi:10.1093/sleep/19.6.465 · Cited by 75 · see citing works
Membrane leakage and increased content of Na+-K+ pumps and Ca2+ in human muscle after a 100-km run
Overgaard, K., Lindstrøm, T., Ingemann-Hansen, T., et al. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00669.2001 · Cited by 75 · see citing works
“One idea that has gained increasing support is that exercise leads to an increase in cytoplasmic Ca2 and that the elevated resting Ca2 level may activate proteolytic enzymes such as calpain to digest essential structural elements of the muscle fibers (4, 11, 17).”
BackgroundSkeletal muscle regeneration after injury: An overview
Bodine, S. C. (1994) · Journal of Voice · doi:10.1016/s0892-1997(05)80319-4 · Cited by 74 · see citing works
Theoretical basis for patterning EMG amplitudes to assess muscle dysfunction
Edgerton, V. R., Wolf, S. L., Levendowski, D. J., et al. (1996) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199606000-00013 · Cited by 74 · see citing works
Effect of eccentric exercise on muscle oxidative metabolism in humans
Walsh, B. J., Tonkonogi, M., Malm, C., et al. (2001) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200103000-00016 · Cited by 74 · see citing works
Vitamin E Status and Response to Exercise Training
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Update on the Relation Between Pain and Movement: Consequences for Clinical Practice
Côté, J. N., & Bement, M. H. (2010) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e3181e0174f · Cited by 71 · see citing works
“Typically pain occurs several hours after the muscular effort.(60) Despite the potential for delayed onset muscle soreness and even though earlier study indicates that pain disrupts motor behavior, controlled exercise paradigms, which may or may not incorporate movement, can manage pain quite effectively.”
BackgroundProlonged exercise induces structural changes in SR Ca2+-ATPase of rat muscle
Luckin, K. A., Favero, T. G., & Klug, G. A. (1991) · Biochemical Medicine and Metabolic Biology · doi:10.1016/0885-4505(91)90087-2 · Cited by 71 · see citing works
Steen, J. P., Jaiswal, K. S., & Kumbhare, D. A. (2025) · Muscle & Nerve · doi:10.1002/mus.28377 · Cited by 98 · see citing works
Cell-free plasma DNA and purine nucleotide degradation markers following weightlifting exercise
Atamaniuk, J., Vidotto, C., Kinzlbauer, M., et al. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1532-5 · Cited by 70 · see citing works
“Generally, weight-lifting exercise induces much more inXammation and/or damage in the muscles than aerobic exercise ( Armstrong 1990, Uchiyama et al. 2006).”
BackgroundLeadbetter, W. B. (1995) · PubMed · Cited by 69 · see citing works
- Authors
- BEN KIBLER, C. W., & ARMSTRONG, R. B.
- Affiliations
- University of Georgia (US)
- Venue
- Medicine & Science in Sports & Exercise
- Published
- 1990-08
- Volume
- 22
- Issue
- 4
- Pages
- 429???435
- ISSN
- 0195-9131 (ISSN-L)
- OpenAlex
- W2052579376
- Cited by
- 457
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 11 · 2019: 15 · 2018: 15 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 20 · 2013: 17 · 2012: 21
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medicine & Science in Sports & Exercise (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2s07rr007025-26, 7r01am037098-01)
- National Center for Research Resources (S07RR-07025-21)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Surgery › Muscle and Compartmental Disorders
- Keywords
- exercise-induced muscle damage, eccentric exercise, sarcomere disruption, myofibril damage, creatine kinase release, delayed onset muscle soreness, intracellular calcium homeostasis, phospholipase A2, leukotrienes, prostaglandins, free radical generation, lysophospholipids
- MeSH terms
- Calcium, Free Radicals, Homeostasis, Humans, Hydrogen-Ion Concentration, Mechanoreceptors, Mitochondria, Muscle, Muscle Contraction, Muscles, Sarcolemma, Sprains and Strains, Exercise
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