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Delayed muscle soreness. The inflammatory response to muscle injury and its clinical implications
Abstract
Delayed onset muscle soreness (DOMS) is a sensation of discomfort that occurs 1 to 2 days after exercise. The soreness has been reported to be most evident at the muscle/tendon junction initially, and then spreading throughout the muscle. The muscle activity which causes the most soreness and injury to the muscle is eccentric activity. The injury to the muscle has been well described but the mechanism underlying the injury is not fully understood. Some recent studies have focused on the role of the cytoskeleton and its contribution to the sarcomere injury. Although little has been confirmed regarding the mechanisms involved in the production of delayed muscle soreness, it has been suggested that the soreness may occur as a result of mechanical factors or it may be biochemical in nature. To date, there appears to be no relationship between the development of soreness and the loss of muscle strength, in that the timing of the two events is different. Loss of muscle force has been observed immediately after the exercise. However, by collecting data at more frequent intervals a second loss of force has been reported in mice 1 to 3 days post-exercise. Future studies with humans may find this second loss of force to be related to DOMS. The role of inflammation during exercise-induced muscle injury has not been clearly defined. It is possible that the inflammatory response may be responsible for initiating, amplifying, and/or resolving skeletal muscle injury. Evidence from the literature of the involvement of cytokines, complement, neutrophils, monocytes and macrophages in the acute phase response are presented in this review. Clinically, DOMS is a common but self-limiting condition that usually requires no treatment. Most exercise enthusiasts are familiar with its symptoms. However, where a muscle has been immobilised or debilitated, it is not known how that muscle will respond to exercise, especially eccentric activity.
... It is commonly experienced by anyone who has undergone unaccustomed exercises and suffered from exerciseinduced muscle damage (EIMD). [1] It is typically experienced by all individuals regardless of their fitness level and is a normal physiological response to increased exertion and introduction of unfamiliar physical activities. [2] DOMS, which occurs 48-72 h after activity, is more common following eccentric contraction due to the significantly greater force produced. ...
... [3][4][5] In addition to pain, DOMS is associated with loss of strength, loss of motion, and swelling of the involved musculature. [1,3] According to Clarkson and Sayers, [6] immediately after exercise, there is up to 60% loss in muscle strength that could persist for 10 days. The pain and discomfort associated with DOMS generally peaks 24-48 h following the activity and resolves itself within 3-7 days without any special treatment. ...
... Evidence indicates that resistance training positively changes mitochondria and microvasculature, improving participants' muscular endurance (Kon et al., 2010;Groennebaek et al., 2018). However, multiple sets of resistance training can cause muscle tissue damage, increased creatine kinase, and decreased neuromuscular status, leading to exercise fatigue and difficulty maintaining specific power output and completing additional repetitions (MacIntyre et al., 1995;González-Hernández et al., 2021;Pareja-Blanco et al., 2017). Additionally, intense resistance training induces delayed onset muscle soreness (DOMS), causing participants to experience discomfort in their skeletal muscles for 24-48 h after exercise (Stauber, 1989;McQuilliam et al., 2023). ...
Background
Exercise-induced oxidative stress and inflammation can impair muscular function in humans. The antioxidant and anti-inflammatory properties of molecular hydrogen (H2) highlight its potential to be as an effective nutritional supplement to support muscular function performance in healthy adults. However, the effects of H2 supplementation on muscular endurance performance in trained individuals have not been well characterized. This study aimed to assess the effects of intermittent hydrogen-rich water (HRW) supplementation before, during, and after resistance training on muscular endurance performance, neuromuscular status, and subjective perceptual responses after a 48-h recovery period.
Methods
This randomized, double-blinded, placebo-controlled cross-over study included 18 trained men aged 19.7 ± 0.9 years. Participants in this study were instructed to consume 1,920 mL of HRW or pure water (Placebo) daily for 7 days. Additionally, participants were required to supplement with HRW or pure water five times during the training day (1,260 mL total). This included drinking 210 mL 30 min and 1 min before training, 210 mL between training sets, 210 mL immediately after training, and 420 mL 30 min into the recovery period. Participants performed half-squat exercises with the load set at 70% of one repetition maximum for six sets (half-squat exercise performed to repetitions failure each set). We measured the power output and number of repetitions in the free barbell half-squat used to assess muscular endurance performance in participants. The countermovement jump (CMJ) height, total quality recovery scale (TQRS), and muscle soreness visual analog scale (VAS) scores were measured to assess fatigue recovery status after training, as well as at 24 and 48 h of recovery.
Results
The total power output (HRW: 50,866.7 ± 6,359.9W, Placebo: 46,431.0 ± 9,376.5W, p = 0.032) and the total number of repetitions (HRW:78.2 ± 9.5 repetitions, Placebo: 70.3 ± 9.5 repetitions, p = 0.019) in the H2 supplemented group were significantly higher than in the placebo group. However, there was no statistically significant difference (p< 0.05) between the H2 and placebo groups in CMJ, TQRS, and VAS.
Conclusion
Eight days of intermittent HRW intake could significantly improve muscular endurance performance in trained individuals, making it a promising strategy for athletes or fitness enthusiasts looking to boost muscular endurance during resistance training or competitions. However, it should be noted that HRW intake alone may not be adequate to accelerate recovery from muscle soreness or fatigue following high-intensity training.
... However, there was no significant difference in muscle soreness reported, indicating that only subjective pain was recorded, which may not be influenced by long-term CP intake. As muscle soreness is also closely related to inflammation [74] and expresses the degree of muscle damage and/ or regeneration at least to some extent [75], animal studies have demonstrated anti-inflammatory potential of CPs and glycine alone. CPs were able to positively modulate local and systemic inflammatory response by reducing swelling and interleukin-6 (IL-6)-mediated lipopolysaccharide (LPS) production, possibly via the activation of glycine-gated chloride channels [76]. ...
Introduction
Over the past decade, collagen peptide (CP) supplements have received considerable attention in sports nutrition research. These supplements have shown promising results in improving personal health, enhancing athletic performance, and preventing injuries in some but not all studies.
Objective
A systematic review and meta-analysis of randomized controlled trials (RCTs) has been conducted to investigate the effects of long-term daily collagen peptide (CP) supplementation on strength, musculotendinous adaptation, functional recovery, and body composition in healthy adults, both with and without concurrent exercise interventions over several weeks.
Methods
The PRISMA with PERSiST guidelines were followed for this systematic literature review, which was conducted in December 2023 using PubMed, Scopus, CINAHL, and SPORTDiscus databases. Eligible studies included healthy, normal to overweight adults over 17 years of age who engaged in exercise and daily collagen peptide (CP) supplementation for a minimum of 8 weeks (except one 3-week trial only included for maximal strength). Studies examining recovery-related outcomes were also eligible if they included a 1-week supplementation period without exercise. Methodological study quality was assessed using the PEDro scale. A random-effects model with standardized mean differences (SMD) of change scores was chosen to calculate overall effect sizes.
Results
Nineteen studies comprising 768 participants were included in both the systematic review and meta-analysis. Results indicate statistically significant effects in favor of long-term CP intake regarding fat-free mass (FFM) (SMD 0.48, p < 0.01), tendon morphology (SMD 0.67, p < 0.01), muscle architecture (SMD 0.39, p < 0.01), maximal strength (SMD 0.19, p < 0.01), and 48 h recovery in reactive strength following exercise-induced muscle damage (SMD 0.43, p = 0.045). The GRADE approach revealed a moderate certainty of evidence for body composition, a very low certainty for tendon morphology and mechanical properties, and a low certainty for the remaining.
Conclusion
This systematic review and meta-analysis represents the first comprehensive investigation into the effects of long-term CP supplementation combined with regular physical training on various aspects of musculoskeletal health in adults. The findings indicate significant, though of low to moderate certainty, evidence of improvements in fat-free mass (FFM), tendon morphology, muscle mass, maximal strength, and recovery in reactive strength following exercise-induced muscle damage. However, further research is required to fully understand the mechanisms underlying these effects, particularly regarding tendon mechanical properties and short-term adaptations to collagen peptide (CP) intake without exercise, as observed in recovery outcomes. Overall, CP supplementation appears promising as a beneficial adjunct to physical training for enhancing musculoskeletal performance in adults.
Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/WCF4Y).
... Delayed onset muscle soreness (DOMS) is defined as the discomfort of muscle groups that occurs 24-48 hours after strenuous exercise and is usually accompanied by a decrease in pain threshold. 45,46 Many studies [47][48][49][50][51] have found that inflammation is an important cause of DOMS and is associated with an increase in mediators such as histamine, bradykinin, neutrophils as well as prostaglandins in the muscle. Another research 52 considered that nerve growth factor (NGF) and derived neurotrophic factor (GDNF) produced by muscle fibers/satellite cells play crucial roles in DOMS. ...
Pinching at specific areas of the human body will produce special sensations, such as soreness, numbness, heaviness and distention, which are collectively referred to as acupuncture sensation. The generation of acupuncture sensation, linked to a variety of receptors and nerve endings in different acupoint areas, induces nerve impulses that are transmitted to the central system through the spinal cord in different patterns. Sensory areas in the cerebral cortex are processed and transformed the impulses to form special sensations. This paper will systematically review the mechanisms of these sensations in different situations, and compare acupuncture sensations to review and analyze the mechanism of acupuncture effect.
This study aimed to assess the levels of delayed onset muscle soreness (DOMS) markers in individuals adhering to vegan and omnivore diets after engaging in acute resistance exercise. A total of 54 untrained young, healthy, normal-body-weight women (age: 26.8±4.1 years; body mass index: 22.5±2.7 kg/m2) participated in the study. Participants were categorized into two groups: vegans (n=27) and omnivores (n=27) based on their dietary preferences, with all subjects having adhered to their respective diets for a minimum of 2 years. DOMS was induced by a single eccentric resistance exercise session, comprising four exercises (leg press, chest press, leg curls, and arm curls), each consisting of four sets of 10 repetitions. Various measurements, including dietary factors, state of wellness, body composition, muscle circumferences, muscle pressure point thresholds (PPTs), and muscle strength, were recorded both before and 48 hours after the exercise session. The results showed that wellness and muscle circumferences remained unchanged or displayed similar changes between the vegan and omnivore groups following acute resistance exercise. However, notable differences were observed in PPTs in favor of vegans, specifically for the right biceps (95% CI: 1.4 to 10.2; p=0.01), the left vastus medialis (95% CI: 0.5 to 6.4; p=0.02), and the right vastus lateralis (95% CI: 3.2 to 12.1; p=0.001). Furthermore, significant differences in right grip strength were found in favor of vegans after the exercise session (95% CI: 3.1 to 26.2; p=0.01). In conclusion, our findings suggest that vegans may experience more favorable changes in DOMS levels following acute resistance exercise in comparison to omnivores. This discrepancy in DOMS markers may indicate enhanced muscle recovery in vegans.
Background
Delayed onset of muscle soreness (DOMS) is a typical physiological response to unaccustomed to intense exercise, characterised by pain, stiffness, and reduced muscle function. DOMS is often experienced in muscles after strenuous limb activities, impacting an individual's physical performance and overall well-being. Effective management strategies for DOMS are essential to minimise discomfort and enhance recovery. In the treatment of DOMS, physiotherapy management is a better option rather than analgesics or NSAIDs. There is a research gap on radial extracorporeal shockwave therapy, rESWT, MFR, cryotherapy, etc. that has an individual and unique effect on pain reduction and functional improvement.
Method
An assessor and participants-blinded randomised clinical trial (RCT) will be used for the investigation. The impact of rESWT, MFR, and stretching combined with cryotherapy on exercise-induced DOMS will be examined in this study. On the patient, DOMS will be induced for research purposes. Three groups will receive rESWT, MFR, and stretching in addition to cryotherapy. After DOMS is induced, the treatment will be given once daily for 0 to 48 hours (3 times in 3 days). Each group will include 40 students, and the research will measure how rESWT, MFR, Cryotherapy, and Stretching affect pain alleviation before treatment (pretest), immediately after treatment (post-test 1), 24 hours later (post-test 2), 48 hours later (post-test 3) and 72 hours later (post-test 4). The outcome metric will be pain intensity and ROM. Male and female students of the University with good physical health and without a history of taking painkillers recently make up the study’s groups.
Discussion
The study investigates the efficacy of physiotherapy approaches (rESWT, MFR, Cryotherapy, and Stretching) on exercise-induced DOMS. It addresses a research gap regarding rESWT’s effectiveness and offers valuable insights into pain reduction methods. The findings can guide comprehensive pain management and individualised recovery strategies.
Trial registration
CTRI/2023/08/056649 [Registered on: 18/08/2023]
Intense, long exercise can increase oxidative stress, leading to higher levels of inflammatory mediators and muscle damage. At the same time, fatigue has been suggested as one of the factors giving rise to delayed-onset muscle soreness (DOMS). The aim of this study was to investigate the efficacy of a specific electrical stimulation (ES) treatment (without elicited muscular contraction) on two different scenarios: in the laboratory on eleven healthy volunteers (56.45 ± 4.87 years) after upper limbs eccentric exercise (Study 1) and in the field on fourteen ultra-endurance athletes (age 47.4 ± 10.2 year) after an ultra-running race (134 km, altitude difference of 10,970 m+) by lower exercising limbs (Study 2). Subjects were randomly assigned to two experimental tasks in cross-over: Active or Sham ES treatments. The ES efficacy was assessed by monitoring the oxy-inflammation status: Reactive Oxygen Species production, total antioxidant capacity, IL-6 cytokine levels, and lactate with micro-invasive measurements (capillary blood, urine) and scales for fatigue and recovery assessments. No significant differences (p > 0.05) were found in the time course of recovery and/or pre–post-race between Sham and Active groups in both study conditions. A subjective positive role of sham stimulation (VAS scores for muscle pain assessment) was reported. In conclusion, the effectiveness of ES in treating DOMS and its effects on muscle recovery remain still unclear.
Running recovery is challenging for several body systems and can be improved by nutritional focus. Non-alcoholic beer is a widely used post-exercise beverage for its antioxidant and energetic properties. After three consecutive days of 1 h submaximal running (80% HRmax), antioxidant enzyme activity (glutathione peroxidase [GPx], glutathione reductase [GR], catalase), lactate dehydrogenase (LDH) activity as a muscle damage blood marker, and lower limb thermographic values were determined in order to observe possible changes in 20 subjects divided into two groups: control (n = 10) and NAB (n = 10). NAB drank 10 mL/kg of non-alcoholic beer post-exercise (both groups drank water ad libitum). Non-alcoholic beer did not show statistically significant changes compared to water. Regarding the effect size, the NAB group had a medium increase in thermography values (15′Post-15′Pre) on days 1 and 2 compared to the control group; a large increase in LDH activity (both 60′Post-0′Post and 60′Post-Pre) on day 2, and a medium increase (60′Post-0′Post) on day 3; a medium decrease in GR (60′Post-Pre) on days 1 and 3; and a large (60′Post-0′Post) and medium (60′Post-Pre) decrease in GPx on day 3. These findings support the idea that non-alcoholic beer is not an appropriate recovery beverage after 1 h running for three consecutive days.
Muscle fatigue can limit performance both in sports and daily life activities. Consecutive days of exercise without a proper recovery time may elicit cumulative fatigue. Although it has been speculated that skin temperature could serve as an indirect indicator of exercise-induced adaptations, it is unclear if skin temperature measured by infrared thermography (IRT) could be an outcome related to the effects of cumulative fatigue. In this study, we recruited 21 untrained women and induced cumulative fatigue in biceps brachii over two consecutive days of exercise. We measured delayed onset muscle soreness (DOMS, using a numeric rate scale), maximal strength (using a dynamometer), and skin temperature (using IRT) in exercise and non-exercise muscles. Cumulative fatigue reduced muscle strength and increased DOMS. Skin temperature in the arm submitted to cumulative fatigue was higher for minimum and mean temperature, being asymmetrical in relation to the control arm. We also observed that the variations in the minimum and mean temperatures correlated with the strength losses. In summary, skin temperature measured by IRT seems promising to help detect cumulative fatigue in untrained women, being useful to explain strength losses. Future studies should provide additional evidence for the potential applications not only in trained participants but also in patients that may not be able to report outcomes of scales or precisely report DOMS.
Exercise-induced muscle damage (EIMD) is a common occurrence in athletes and can lead to delayed onset muscle soreness, reduced athletic performance, and an increased risk of secondary injury. EIMD is a complex process involving oxidative stress, inflammation, and various cellular signaling pathways. Timely and effective repair of the extracellular matrix (ECM) and plasma membrane (PM) damage is critical for recovery from EIMD. Recent studies have shown that the targeted inhibition of phosphatase and tension homolog (PTEN) in skeletal muscles can enhance the ECM environment and reduce membrane damage in Duchenne muscular dystrophy (DMD) mice. However, the effects of PTEN inhibition on EIMD are unknown. Therefore, the present study aimed to investigate the potential therapeutic effects of VO-OHpic (VO), a PTEN inhibitor, on EIMD symptoms and underlying mechanisms. Our findings indicate that VO treatment effectively enhances skeletal muscle function and reduces strength loss during EIMD by upregulating membrane repair signals related to MG53 and ECM repair signals related to the tissue inhibitor of metalloproteinases (TIMPs) and matrix metalloproteinase (MMPs). These results highlight the potential of pharmacological PTEN inhibition as a promising therapeutic approach for EIMD.
The effects of one 45-min bout of high-intensity eccentric exercise (250 W) were studied in four male runners and five untrained men. Plasma creatine kinase (CK) activity in these runners was higher (P less than 0.001) than in the untrained men before exercise and peaked at 207 IU/ml 1 day after exercise, whereas in untrained men the maximum was 2,143 IU/ml 5 days after exercise. Plasma interleukin-1 (IL-1) in the trained men was also higher (P less than 0.001) than in the untrained men before exercise but did not significantly increase after exercise. In the untrained men, IL-1 was significantly elevated 3 h after exercise (P less than 0.001). In the untrained group only, 24-h urines were collected before and after exercise while the men consumed a meat-free diet. Urinary 3-methylhistidine/creatinine in the untrained group rose significantly from 127 mumol/g before exercise to 180 mumol/g 10 days after exercise. The results suggest that in untrained men eccentric exercise leads to a metabolic response indicative of delayed muscle damage. Regularly performed long distance running was associated with chronically elevated plasma IL-1 levels and serum CK activities without acute increases after an eccentric exercise bout.
Eight male subjects (mean age 24.1 +/- 2.6 years) performed at intervals of 2 weeks successively a 3 h and two 2 h runs of different running speed. The days following the running there were moderate elevations of C-reactive protein, haptoglobin, alpha-1-acid glycoprotein, coeruloplasmin, transferrin, alpha-1-antitrypsin and plasminogen. There were small or no changes of albumin, alpha-2-macroglobulin and hemopexin. The elevations of the "acute phase reactants" were examined in three male subjects following a 2 h run before and after an endurance training period of 9 weeks. This demonstrated a decreased acute phase response after training as illustrated by the changes of C-reactive protein, haptoglobin and alpha-1-acid glycoprotein in spite of higher posttraining running speeds. Well-trained athletes have elevated levels of the serum protease inhibitors alpha-1-antitrypsin, alpha-2-macroglobulin and C1-inhibitor. These antiproteolytic glycoproteins might limit exercise-induced inflammatory reactions.
This chapter elaborates about painful disorders of muscle. Most healthy people will have experienced muscle pain due to cramp or due to vigorous sustained voluntary contraction. Exercise-induced muscle pain is similar in quality to that of intermittent claudication and is thought to be caused by the release of some putative pain substance or substances from contracting fibers. The identity of the nociceptive substance is not known. In the untrained subject, protracted muscle pain and tenderness can persist for hours or even days after unaccustomed exercise. Skeletal muscle is also sensitive to firm pressure and to direct trauma such as that occurs during electromyography or at the time of muscle biopsy. Many patients who present with muscle pain remain undiagnosed even after the most careful and detailed investigation. Clinical examination usually shows normal results, although muscle strength is sometimes restricted by pain. Although vague muscle aches and pains are relatively common in depression and other emotional disorders, these patients rarely, if ever, show any other evidence of psychiatric disturbance and their symptoms usually remain sufficiently consistent over the years to indicate that they have an organic basis.
Eleven male subjects took part in a 100 km running competition. Alterations in the total plasma protein and in ten individual plasma protein concentrations in blood and urine were measured prior to the run, immediately after and after 1 day of recovery. Five individual proteins showed a 7–10%, and lysozyme a 40%, increase in the plasma after the run. On the contrary, the haptoglobin concentration fell to 40% of its pre-race level. None of these variations were correlated with the plasma volume change. The present data showed a moderate hemolysis, as evidenced by plasma lysozyme and hemoglobin-haptoglobin binding. The urinary excretion of plasma proteins was slightly increased, especially albumin and α
1-acid-glycoprotein. The renal clearance of plasma proteins revealed that the 100 km run induced a moderate increase of glomerular permeability without any significant change in the tubular reabsorption process.
1. After severe muscular contraction in man recovery of force is largely complete in a few minutes, but is not wholly so for many hours. The long-lasting element of fatigue is found to occur primarily for low frequencies of stimulation (e.g. 20/sec), and is much less pronounced, or absent, at high frequencies (80/sec). The twitch force is an unreliable measure of the state of fatigue. 2. The long-lasting element of fatigue is not due to depletion of high-energy phosphate nor is it due to failure of electrical activity as recorded from surface electrodes. It is probably the result of an impairment of the process of excitation-contraction coupling. Its practical importance for man could be significant as an explanation of the subjective feelings of weakness following exercise.
Plasma volume, hematocrit, intravascular protein concentration, colloid osmotic pressure and the intravascular mass of proteins were measured in 49 sedentary subjects and 40 endurance athletes (long-, middle distance runners, cyclists). The plasma volume in sedentary subjects was 42.7(35.8-51.7) ml/kg body weight (BW) as compared to 54.6(46.7-65.9) ml/kg BW in athletes. The protein concentrations were 71.0 (66.5-77.1) g/l in sedentary subjects and 69.0 (64.8-75.2) g/l in athletes. The respective numbers for the hematocrit were 44.6 (40.1-49.25)% and 42.8 (38.2-49.6)%, for the colloid osmotic pressure 38.0 (36.0-40.5) cm H2O (n=35) and 30.0 (25.0-34.4) cm H2O (n=31), for the intravascular mass of proteins 3.09 (2.45-4.01) g/kg BW and 3.75 (3.31-4.67) g/kg BW. All differences were statistically significant at least on the 5% level. The physiological consequences for athletes of having a lower hematocrit and lower protein concentration but a higher intravascular mass of proteins (+22%) for their waterbalance as well as for their dietary protein intake are discussed. Endurance exercise stimulates mainly the synthesis of albumin and globulins produced by the liver resulting in an expansion of the PV. The protein synthesis of the RES does not seem to respond to exercise stimulus.