Delayed onset muscle soreness (DOMS) is the tender, stiff ache that appears in muscles hours after unaccustomed exercise, peaks a day or two later and fades within about a week. It follows mainly eccentric contractions, in which a muscle lengthens while it pulls, and it is a well-studied model of how mechanical strain on tissue becomes pain.
This guide covers the time course, causes and mechanism of DOMS, how it is measured, the repeated bout effect, how it differs from a strain, and what peptide research does and does not show.
The short answer
- It is delayed tenderness. DOMS typically begins 12 to 24 hours after unaccustomed exercise, peaks at 24 to 72 hours and resolves within 5 to 7 days; the muscle is tender when pressed, stretched or contracted.
- Eccentric contractions cause most of it. A muscle lengthening under load, as the thighs do in downhill running, makes high force with few active fibres, and its weakest sarcomeres can be overstretched.
- Lactic acid is not the cause. Lactate returns to pre-exercise levels within about an hour, long before soreness peaks.
- Sensitized nerves appear to produce the pain. In rats, bradykinin acting on B2 receptors during exercise leads muscle to make nerve growth factor (NGF), and COX-2 leads it to make GDNF; both sensitize nociceptors.
- Soreness is a poor gauge of damage. In 110 men, palpation soreness did not correlate with any other damage marker, and peak creatine kinase can vary more than a hundredfold between people doing the same exercise.
- One bout protects the next. In one study the repeated bout effect lasted at least 6 months and was gone by 12.
- The peptides discussed here have not been tested in DOMS. We found no such study of ARA-290, BPC-157 or thymosin beta-4; ARA-290 has been studied in rat nerve-injury pain and a 64-person neuropathy trial, and BPC-157 and thymosin beta-4 in rodent muscle-injury models.
Delayed onset muscle soreness (DOMS)
muscle soreness after exercise · exercise-induced muscle soreness
- What it is
- Delayed tenderness and stiffness in exercised muscle
- Timing
- Starts at 12–24 h, peaks at 24–72 h, gone within about 7 days
- Main trigger
- Eccentric (lengthening) contractions
- Not the cause
- Lactic acid, cleared within about an hour
- Pain route (rats)
- Bradykinin → NGF; COX-2 → GDNF; sensitized nociceptors
- Classification
- Functional muscle disorder, no macroscopic fibre tear
Where the evidence stands
- Time course measured in people
- Pain pathway mapped in rats
- NGF tested in volunteers
- Mechanism confirmed in human muscle
The time course and eccentric trigger are well established in people; the growth-factor routes come from rats, and the human evidence for them is indirect.
What delayed onset muscle soreness is
Delayed onset muscle soreness is the soreness, stiffness and tenderness that develops in skeletal muscle after unaccustomed exercise, especially exercise heavy in eccentric contractions. In the classic description there is a pain-free period of 12 to 24 hours, soreness peaks between 24 and 72 hours and it resolves within 5 to 7 days; the 2013 Munich consensus on muscle-injury terminology says it usually resolves on its own within a week.
Sore muscles of this kind are above all tender: they hurt when pressed, stretched or contracted, which physiologists call mechanical hyperalgesia. Strength, range of motion and swelling change too. In a University of British Columbia study of 10 women who performed 300 eccentric quadriceps repetitions, soreness peaked at 24 hours while eccentric strength dipped twice, immediately and again at 24 hours, which the authors took as a sign of more than one mechanism. Soreness also tends to fade before muscle function has fully recovered.
Why eccentric contractions cause DOMS
An eccentric contraction happens when an external force exceeds the force a muscle is producing, so the muscle–tendon unit lengthens while active, as the quadriceps do when braking each step of a downhill run. At the same speed, an eccentric contraction generates more force than a concentric one, and for a given force it activates fewer motor units; a 2019 review puts its metabolic cost at roughly a quarter of the same exercise done concentrically.
The leading explanation for the damage is the popping-sarcomere hypothesis, proposed by David Morgan in 1990: when an active muscle is stretched, the weakest sarcomeres take up most of the length change and can be pulled beyond the point where their filaments overlap. Damage is greater at longer muscle lengths, and disturbed calcium handling can activate calpains, enzymes that cleave structural proteins such as desmin.
Contraction type matters more than effort. In a 1983 study, seven people ran downhill on a 10% grade for 45 minutes at about 57% of maximal oxygen uptake and, on another occasion, on the level at a harder 78%; only the downhill run produced significant soreness and a rise in plasma creatine kinase. In rats, only downhill treadmill running produced a late rise in plasma muscle enzymes 1.5 to 2 days later.
Why lactic acid is not the cause
The idea that lactic acid builds up and causes next-day soreness has been strongly discredited. Lactate rises during hard exercise but returns to pre-exercise levels within about an hour, so it cannot be present when soreness peaks a day or more later. And concentric exercise, which carries the higher metabolic load, rarely produces DOMS.
| Common belief | What the evidence shows |
|---|---|
| Lactic acid causes it | Lactate clears within about an hour; soreness peaks at 24 to 72 hours |
| Harder workouts cause more soreness | Contraction type matters more: an easier downhill run caused soreness that a harder level run did not |
| Soreness shows how much muscle was damaged | Palpation soreness did not track other damage markers in 110 men |
| Inflammatory cells cause the pain | White-cell accumulation tracked strength loss, not soreness |
| It all happens in the muscle fibres | The surrounding fascia becomes more sensitive after eccentric exercise |
| The same exercise will hurt as much next time | A first bout protects against the next, in one study for at least 6 months |
What makes the muscle sore: the current picture
No single mechanism explains DOMS. The evidence points to three overlapping processes: inflammation, changes in connective tissue, and chemical sensitization of the nerve endings that signal muscle pain.
Inflammation and immune cells
In the British Columbia study, radiolabelled white blood cells gathered in the exercised quadriceps over the first 24 hours. A later study of 300 maximal eccentric quadriceps actions found leukocytes accumulating within roughly 3 to 24 hours, mainly in the connective tissue around fibres, with CD16- and CD68-positive cells most numerous at day 4; their accumulation correlated with lost strength, while soreness could not be explained by the leukocytes. Tightly regulated inflammation is now considered integral to muscle repair and regeneration, much as in the four overlapping phases of tissue repair.
Connective tissue and fascia
A 2021 review describes human studies in which the fascia, not the muscle, became more sensitive after eccentric exercise: hypertonic saline, an experimental pain stimulus, hurt more in the fascia of a leg exercised the day before, while muscle pain was unchanged. Fascia is densely innervated, and collagen-breakdown markers such as hydroxyproline rise after eccentric exercise, though not in step with soreness; see our guide to types of collagen.
The nociceptor-sensitization pathway
The most detailed mechanism comes from Kazue Mizumura, Toru Taguchi and colleagues, who produce DOMS-like tenderness in rats by stimulating the common peroneal nerve while stretching the extensor digitorum longus. Tenderness of the muscle, but not of the overlying skin, appears 1 to 3 days later, with no fibre damage visible by light microscopy.
In the rat model, one route starts when the inflammatory mediator bradykinin, a nine-residue peptide, acts during exercise on B2 receptors, members of the G protein-coupled receptor family. From about 12 hours to 2 days later, nerve growth factor (NGF; see our neurotrophic factors guide) rises in the exercised muscle and sensitizes thin-fibre muscle afferents to mechanical stimulation; bradykinin alone, without contractions, did not reproduce the tenderness. In the other route, COX-2 rises within 12 hours and glial cell line-derived neurotrophic factor (GDNF) between 12 hours and 1 day. Blocking B2 receptors or COX-2 before the contractions prevented the tenderness, blocking them at day 2 did not reverse it, and antibodies against NGF or GDNF given at day 2 reversed it fully or partly. The group links the sensitization to TRPV1, acid-sensing ion channels and TRPV4, and concludes that fibre damage is sufficient but not essential for DOMS.
Rat data, not advice. The receptor blockers, enzyme inhibitors and antibodies above were research tools in rats. The results are not evidence about pain relievers or any other intervention in people.
The human evidence is indirect: in volunteers given NGF in one trapezius and saline in the other before eccentric shoulder exercise, the NGF side became more tender to pressure. That shows NGF can intensify DOMS-type tenderness in people, not that the rat chain produces DOMS in human muscle.
The recovery and repair range, including ARA-290, TB-500 and BPC-157, is sold as laboratory reagents priced in CAD.
Browse recovery & repairHow DOMS is studied and measured
Human and animal models
Human studies use controlled bouts of lengthening contractions: maximal eccentric actions of the elbow flexors (in one study of 110 men, groups did 12, 24 or 60), repeated eccentric knee extensions, or downhill running. Outcomes include maximal isometric force, range of motion, limb circumference, soreness on a visual analogue scale, plasma creatine kinase and MRI T2 relaxation time. In rats, downhill treadmill running on a 16-degree grade was described as an eccentric injury model in 1983, and the nerve-stimulation model measures muscle tenderness with the Randall–Selitto pressure test.
Creatine kinase: a damage marker that tracks soreness poorly
Creatine kinase (CK) is a muscle enzyme that appears in the blood when fibres are damaged; after the 1983 downhill run it was about 351% above baseline at 24 hours. As a guide to soreness it falls short. Among 10 men doing the same 24 maximal eccentric elbow-flexor actions, peak CK varied more than a hundredfold, and in the 110-man study palpation soreness showed no significant correlation with any other damage indicator, leading the authors to call DOMS a poor reflector of muscle damage and inflammation.
The repeated bout effect
The repeated bout effect is the adaptation by which a single bout of eccentric exercise protects muscle against damage from later bouts. When 35 men repeated an eccentric elbow-flexor bout after 6, 9 or 12 months, the 6-month group showed less soreness, smaller rises in CK and faster strength recovery; the authors concluded that the effect lasts at least 6 months and is lost between 9 and 12. Proposed explanations are neural, mechanical and cellular, and no unified theory explains it, though protection with electrically stimulated contractions points to an adaptation within the muscle itself. In rats, a second bout produced less tenderness and less NGF upregulation.
DOMS vs an acute muscle strain
The Munich consensus classifies DOMS as a functional muscle disorder, without macroscopic evidence of fibre tear, whereas a strain, or pulled muscle, is a structural injury, which the consensus prefers to call a tear.
| Feature | DOMS | Acute muscle strain |
|---|---|---|
| Onset | Hours after unaccustomed exercise | Acute, during the activity |
| Mechanism | Repeated eccentric contractions | Sudden forced lengthening beyond the muscle’s viscoelastic limits |
| Tissue | No macroscopic fibre tear | Partial to complete tear |
Physiology, not diagnosis. This table summarizes how researchers classify the two conditions; it is not a tool for identifying an injury.
Where research peptides come in
We found no published study testing any of the peptides below on DOMS, in animals or people; the closest work is in neighbouring models of nerve pain and muscle injury. Our guide on how to read a peptide study explains what each evidence level can show.
ARA-290 and the innate repair receptor
ARA-290 (cibinetide), a peptide derived from the tertiary structure of erythropoietin, is described in its trials as an innate repair receptor agonist; that receptor is proposed to pair the erythropoietin receptor with the beta common subunit, separate from the receptor that drives red-cell production. In rats with spared nerve injury it reduced mechanical allodynia for up to 20 weeks. In a 28-day phase 2b trial in 64 people with sarcoidosis-associated small nerve fibre loss, the primary endpoint was significant only in the middle of three active arms, and pain fell in all groups, placebo included. None of this work involved exercise; see our ARA-290 research guide.
Rodent muscle-injury studies
BPC-157, a gastric pentadecapeptide, was given to rats with a surgically transected quadriceps, and over 72 days those rats had better biomechanical, functional and microscopic scores than controls. For thymosin beta-4, sold for research as TB-500, the muscle work cited here is in mice and cells: its mRNA rose early after muscle injury in mice, it attracted C2C12 myoblasts in culture, and in dystrophin-deficient mice given it for 6 months regenerating fibres increased, but grip strength, heart function and fibrosis did not significantly change. A transected or dystrophic muscle is not a sore one. See BPC-157 vs TB-500, the BPC-157 safety review and TB-500 vs TB-500 Fragment.
What’s established and what isn’t
Reasonably well established
- DOMS starts hours after unaccustomed exercise, peaks at 24 to 72 hours and usually resolves within a week.
- Eccentric contractions, not lactic acid, are the main cause.
- Soreness is a poor measure of muscle damage.
- One eccentric bout protects against later bouts for months.
- DOMS involves no macroscopic fibre tear, unlike a strain.
Open questions
- Whether the rat bradykinin–NGF and COX-2–GDNF routes operate in human muscle.
- How much of the pain arises in the fascia.
- What causes the repeated bout effect.
- Why creatine kinase and soreness responses vary so much between people.
- How rodent findings for BPC-157, thymosin beta-4 and ARA-290 relate to exercise-induced soreness, which none of them modelled.
Sourcing muscle and pain research peptides in Canada
Nociception and muscle-injury assays are sensitive to what is in the vial. When buying research peptides in Canada for this work:
- Ask for a batch-matched certificate with identity by mass spectrometry and purity by HPLC; see our peptide COA guide.
- Confirm the molecule: TB-500 can mean full-length thymosin beta-4 or a short fragment, so check the identity mass.
- Store lyophilized material cold, dry and dark; see the peptide storage guide and our overview of research peptides in Canada.
ARA-290Innate repair receptor agonist used in nerve and pain researchView product
TB-500Thymosin beta-4, studied in myoblast migration and mouse muscle modelsView product
BPC-157Gastric pentadecapeptide studied in rat muscle-injury modelsView product
Research use only. Pure Peptides Canada products are laboratory reagents for in-vitro research, not for human or veterinary use. This article explains published research for education; it is not medical, dietary or dosing guidance.
Frequently asked questions
What is delayed onset muscle soreness (DOMS)?
Delayed onset muscle soreness is the tenderness, stiffness and aching that develops in muscles hours after unaccustomed exercise, especially eccentric exercise such as downhill running. It typically begins 12 to 24 hours afterwards, peaks between 24 and 72 hours and resolves within about a week.
How long does DOMS last?
DOMS usually follows a pain-free period of 12 to 24 hours, peaks between 24 and 72 hours after exercise and resolves within 5 to 7 days. Muscle strength can take longer to return than the soreness does.
Is DOMS caused by lactic acid?
No. Lactate returns to pre-exercise levels within about an hour after exercise, long before soreness peaks. Concentric exercise, which has a higher metabolic cost, rarely produces DOMS, while an easier downhill run can.
Why do eccentric exercises cause more muscle soreness?
In an eccentric contraction the muscle lengthens while producing force, generating high tension with relatively few active fibres, so the weakest sarcomeres can be overstretched. In rats, lengthening contractions, but not shortening contractions or stretching alone, also trigger growth-factor signalling that sensitizes pain nerves.
Does muscle soreness mean muscle damage?
Not reliably. In a study of 110 men, soreness on palpation did not correlate significantly with any other marker of muscle damage, and the authors called DOMS a poor reflector of damage and inflammation. In rats, DOMS-like tenderness develops without visible fibre damage.
What is the difference between DOMS and a pulled muscle?
DOMS is a functional muscle disorder that develops hours after unaccustomed exercise, with no macroscopic tear of muscle fibres. A pulled muscle, or strain, is a structural tear, usually at the muscle-tendon junction, caused by sudden forced lengthening. This describes how researchers classify the two, not how to diagnose an injury.
What is the repeated bout effect?
It is the protection that a single bout of eccentric exercise gives against muscle damage and soreness from later bouts. In one study of 35 men, the protection lasted at least 6 months and was lost between 9 and 12 months.
Research peptides for muscle and pain studies, from a Canadian supplier
ARA-290, TB-500, BPC-157 and related research peptides for laboratory work, priced in Canadian dollars and shipped tracked from inside Canada. Checkout accepts credit and debit cards, Interac e-Transfer and cryptocurrency.
References
- Armstrong RB, Ogilvie RW, Schwane JA. Eccentric exercise-induced injury to rat skeletal muscle. J Appl Physiol. 1983;54(1):80–93. DOI
- Schwane JA, Johnson SR, Vandenakker CB, Armstrong RB. Delayed-onset muscular soreness and plasma CPK and LDH activities after downhill running. Med Sci Sports Exerc. 1983;15(1):51–56. DOI
- MacIntyre DL, Reid WD, Lyster DM, Szasz IJ, McKenzie DC. Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise. J Appl Physiol. 1996;80(3):1006–1013. DOI
- Nosaka K, Clarkson PM. Variability in serum creatine kinase response after eccentric exercise of the elbow flexors. Int J Sports Med. 1996;17(2):120–127. DOI
- Nosaka K, Sakamoto K, Newton M, Sacco P. How long does the protective effect on eccentric exercise-induced muscle damage last? Med Sci Sports Exerc. 2001;33(9):1490–1495. DOI
- Nosaka K, Newton M, Sacco P. Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage. Scand J Med Sci Sports. 2002;12(6):337–346. DOI
- McHugh MP. Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise. Scand J Med Sci Sports. 2003;13(2):88–97. DOI
- Brines M, Grasso G, Fiordaliso F, et al. Erythropoietin mediates tissue protection through an erythropoietin and common β-subunit heteroreceptor. Proc Natl Acad Sci U S A. 2004;101(41):14907–14912. DOI
- Taguchi T, Matsuda T, Tamura R, Sato J, Mizumura K. Muscular mechanical hyperalgesia revealed by behavioural pain test and c-Fos expression in the spinal dorsal horn after eccentric contraction in rats. J Physiol. 2005;564(Pt 1):259–268. DOI
- Staresinic M, Petrovic I, Novinscak T, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res. 2006;24(5):1109–1117. DOI
- Nie H, Madeleine P, Arendt-Nielsen L, Graven-Nielsen T. Temporal summation of pressure pain during muscle hyperalgesia evoked by nerve growth factor and eccentric contractions. Eur J Pain. 2009;13(7):704–710. DOI
- Murase S, Terazawa E, Queme F, et al. Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed-onset muscle soreness). J Neurosci. 2010;30(10):3752–3761. DOI
- Paulsen G, Crameri RM, Benestad HB, et al. Time course of leukocyte accumulation in human muscle after eccentric exercise. Med Sci Sports Exerc. 2010;42(1):75–85. DOI
- Spurney CF, Cha HJ, Sali A, et al. Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin β-4 in the dystrophin deficient mouse. PLoS One. 2010;5(1):e8976. DOI
- Tokura Y, Nakayama Y, Fukada S, et al. Muscle injury-induced thymosin β4 acts as a chemoattractant for myoblasts. J Biochem. 2011;149(1):43–48. DOI
- Murase S, Terazawa E, Hirate K, et al. Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats. J Physiol. 2013;591(12):3035–3048. DOI
- Mueller-Wohlfahrt HW, Haensel L, Mithoefer K, et al. Terminology and classification of muscle injuries in sport: the Munich consensus statement. Br J Sports Med. 2013;47(6):342–350. DOI
- Swartjes M, van Velzen M, Niesters M, et al. ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. Mol Pain. 2014;10:13. DOI
- Mizumura K, Taguchi T. Delayed onset muscle soreness: involvement of neurotrophic factors. J Physiol Sci. 2016;66:43–52. DOI
- Peake JM, Neubauer O, Della Gatta PA, Nosaka K. Muscle damage and inflammation during recovery from exercise. J Appl Physiol. 2017;122(3):559–570. DOI
- Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain. Invest Ophthalmol Vis Sci. 2017;58(6):BIO52–BIO60. DOI
- Hody S, Croisier JL, Bury T, Rogister B, Leprince P. Eccentric muscle contractions: risks and benefits. Front Physiol. 2019;10:536. DOI
- Wilke J, Behringer M. Is “delayed onset muscle soreness” a false friend? The potential implication of the fascial connective tissue in post-exercise discomfort. Int J Mol Sci. 2021;22(17):9482. DOI
- UniProt Consortium. UniProtKB entries P01042 (kininogen-1, bradykinin) and P30411 (B2 bradykinin receptor). UniProt
For laboratory research use only. Not for human or veterinary use. This article summarizes published research for educational purposes and is not medical advice.
