Content uploaded by W Darlene Reid
Author content
All content in this area was uploaded by W Darlene Reid on Apr 07, 2014
Content may be subject to copyright.
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.
... Thus, high-intensity eccentric muscle work causes substantial overstretching of sarcomeres with signs of structural muscle damage (Mekjavic et al. 2000;Proske and Morgan 2001;Fridén et al. 1981;Newham et al. 1983), triggering a local inflammatory response (Newham 1988;MacIntyre et al. 1995), signified by oedema and soreness, often referred to as delayed-onset muscle soreness (DOMS) (MacIntyre et al. 1995;Jones et al. 1987;Newham et al. 1983;Ebbeling and Clarkson 1989). Typically, maximal voluntary contraction force (MCV) can be reduced by 50% immediately after a bout of highintensity eccentric exercise and remain significantly reduced 24 and 48 h after the exercise (Clarkson et al. 1992;Prasartwuth et al. 2005). ...
... Thus, high-intensity eccentric muscle work causes substantial overstretching of sarcomeres with signs of structural muscle damage (Mekjavic et al. 2000;Proske and Morgan 2001;Fridén et al. 1981;Newham et al. 1983), triggering a local inflammatory response (Newham 1988;MacIntyre et al. 1995), signified by oedema and soreness, often referred to as delayed-onset muscle soreness (DOMS) (MacIntyre et al. 1995;Jones et al. 1987;Newham et al. 1983;Ebbeling and Clarkson 1989). Typically, maximal voluntary contraction force (MCV) can be reduced by 50% immediately after a bout of highintensity eccentric exercise and remain significantly reduced 24 and 48 h after the exercise (Clarkson et al. 1992;Prasartwuth et al. 2005). ...
... Seven days might not have been enough to completely restore the EIMD; however, it appears from indirect markers of muscle damage (i.e. drop in strength, soreness and biomarkers) that the affected muscle will almost, if not completely, recover by day 7 after a maximal eccentric bout (MacIntyre et al. 1995;Jones et al. 1987). In the present study, the interval between the exposures carried out in the order CNT-ECC was (mean (range)) 12 (5-28) days and for ECC-CNT order it was 16 (8-28) days. ...
Purpose: Animal studies have shown that recent musculoskeletal injuries increase the risk of decompression sickness (DCS). However, to date no similar experimental study has been performed in humans. The aim was to investigate if exercise-induced muscle damage (EIMD) - as provoked by eccentric work and characterized by reduced strength and delayed onset muscle soreness (DOMS) - leads to increased formation of venous gas emboli (VGE) during subsequent hypobaric exposure.
Methods: Each subject (n=13) was on two occasions exposed to a simulated altitude of 24000 ft for 90 min, whilst breathing oxygen. Twenty-four hrs prior to one of the altitude exposures, each subject performed 15 min of eccentric arm-crank exercise. Markers of EIMD were reduction in isometric m. biceps brachii strength and DOMS as assessed on the Borg CR10 pain scale. The presence of VGE was measured in the right cardiac ventricle using ultrasound, with measurements performed at rest and after three leg kicks and three arm flexions. The degree of VGE was evaluated using the 6-graded Eftedal Brubakk scale and the Kisman integrated severity score (KISS).
Results: Eccentric exercise induced DOMS (median 6.5), reduced the biceps brachii strength (from 230 ± 62 N to 151 ± 8.8 N) and increased the median KISS at 24000 ft, both at rest (from 1.2 ± 2.3 to 6.9 ± 9.2, p=0.01) and after arm flexions (from 3.8 ± 6.2 to 15.5 ± 17.3, p=0.029).
Conclusion: EIMD, induced by eccentric work, provokes release of VGE in response to acute decompression.
... DOMS is pain or discomfort that develops commonly between 24 and 48 h after unaccustomed, eccentric, or intense and prolonged exercise sessions (Bussulo et al. 2021;Nicol et al. 2015;Cheung et al. 2003;MacIntyre et al. 1995). Clinically, DOMS is classified as an overexertion-functional muscle disorder type Ib. ...
... It is likely that when walking up-and downstairs and sitting down and getting up, several muscle groups are active, which may increase the sensation of pain in the lower limbs as a whole, which does not happen during passive palpation of specific regions in the quadricep muscle. In DOMS, intramuscular edema occurs as a result of the inflammatory response orchestrated after EIMD (Heiss et al. 2019;MacIntyre et al. 1995). During inflammation, increases in interstitial fluid pressure occur in tissues (Scallan et al. 2010), which under manual pressure is further intensified. ...
Purpose
Delayed-onset muscle soreness (DOMS) describes an entity characterized by ultrastructural muscle damage. Hesperidin methyl chalcone (HMC) is a synthetic flavonoid presenting analgesic, anti-inflammatory, and antioxidant properties. We evaluated the effects of HMC upon DOMS.
Method
In a preventive paradigm, 31 sedentary young men were submitted to a randomized, double-blinded parallel trial and received HMC 500 mg or one placebo capsule × 3 days before an intense dynamic exercise protocol (concentric/eccentric actions) applied for lower limbs for inducing muscle damage. Assessments were conducted at baseline, and 24 and 48 h after, comprising physical performance, and post-muscle soreness and damage, inflammation, recovery of muscle strength, and postural balance associated with DOMS. HMC safety was also evaluated. Thirty participants completed the study.
Results
HMC improved the performance of participants during exercise (40.3 vs 51.3 repetitions to failure, p = 0.0187) and inhibited CPK levels (90.5 vs 57.9 U/L, p = 0.0391) and muscle soreness during passive quadriceps palpation (2.6 vs 1.4 VAS cm, p = 0.0439), but not during active actions, nor did it inhibit IL-1β or IL-10 levels. HMC improved muscle strength recovery, and satisfactorily refined postural balance, without inducing injury to kidneys or liver.
Conclusions
Preemptive HMC supplementation may be beneficial for boosting physical performance and for the amelioration of clinical parameters related to DOMS, including pain on muscle palpation, increased blood CPK levels, and muscle strength and proprioceptive deficits, without causing adverse effects. These data advance the understanding of the benefits provided by HMC for DOMS treatment, which supports its usefulness for such purpose.
... 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.
... Exercise-induced muscle damage is typically accompanied by muscle soreness that lasts for several days after exercise. While the mechanisms underpinning the phenomenon of exercise-induced DOMS is unclear, several hypotheses implicate the role of mechanical and biochemical factors in the development and dissipation of DOMS post-exercise [3,17]. Among these biochemical factors are the inflammatory mediators bradykinin [22] and prostaglandin E 2 (PGE 2 ) [30] that are upregulated following exercise-induced muscle damage by infiltrating immune cells or muscle tissue. ...
Purpose
The mechanisms that underpin exercise-induced muscle damage and recovery are believed to be mediated, in part, by immune cells recruited to the site of injury. The aim of this study was to characterise the effects of muscle damage from bench-stepping on circulating cytokine and immune cell populations post-exercise and during recovery.
Methods
Ten untrained, healthy male volunteers completed 30 min of bench-stepping exercise to induce muscle damage to the eccentrically exercised leg. Muscle function, muscle pain and soreness were measured before, immediately after and 24, 48 and 72 h after exercise. Plasma creatine kinase, cartilage oligomeric matrix protein, cytokines and circulating immune cell phenotyping were also measured at these timepoints.
Results
Significant decreases occurred in eccentric, isometric and concentric ( P = 0.018, 0.047 and 0.003, respectively) muscle function in eccentrically, but not concentrically, exercised quadriceps post-exercise. Plasma monocyte chemoattractant protein (MCP)-1 concentrations significantly increased immediately after exercise (69.0 ± 5.8 to 89.5 ± 10.0 pg/mL), then declined to below pre-exercise concentrations (58.8 ± 6.3 pg/mL) 72 h after exercise. These changes corresponded with the significant decrease of circulating CD45 ⁺ CD16 ⁻ CD14 ⁺ monocytes (5.8% ± 1.5% to 1.9% ± 0.5%; Pre-exercise vs. 48 h) and increase of CD45 ⁺ CD3 ⁺ CD56 ⁻ T-cells (60.5% ± 2.2% to 66.1% ± 2.1%; Pre-exercise vs. 72 h) during recovery.
Conclusion
Bench-stepping induced muscle damage to the quadriceps, which mediated systemic changes in MCP-1, monocytes and T-cells immediately post-exercise and during recovery. Further research is needed to clarify how modulations in immune subpopulations facilitate muscle recovery and adaptation following muscle damage.
... Indeed, healing cannot occur without inflammation (Hart, 2002). Current evidence suggests that this process evolves rapidly, often within minutes (MacIntyre, Reid, & McKenzie, 1995). The primary positive outcome of inflammation is the repair of injured tissue (Tidball, 1995). ...
Dissertation for PhD at The University of Texas at Austin. Department of Kinesiology and Health Education. ABSTRACT: A large body of evidence supports the notion that chronic stress and strain may impact healing from physical trauma. However, no evidence exists to substantiate whether chronic stress impacts recovery from exercise-induced muscle damage. In this study, a group of 31 undergraduate weight-training students completed the Perceived Stress Scale (PSS), Undergraduate Stress Survey (USQ, a measure of life event stress) a series of fitness tests and then returned 5 to 10 days later for an exhaustive resistance exercise stimulus (E-RES) workout. This workout was performed on a leg press to the cadence of a metronome to ensure a strong eccentric component of exercise. Participants were monitored for 1 hour after this workout and every day for 4 days afterwards. Hierarchical Linear Modeling (HLM) multi-level growth curve analyses demonstrated that stress measures were related to recovery from maximal resistance exercise for both functional muscular (maximal isometric force, jump height, and cycling power) and psychological (perceived energy, perceived fatigue, and soreness) outcomes. Stress was not related to outcomes immediately post-workout (except maximal cycling power) after controlling for pre-workout values. Thus, the effect of stress on recovery is not likely due to magnitude of disruption from maximal exercise. After controlling for significant covariates, including fitness and percent disruption from baseline, individuals scoring a 10 on the PSS at their first visit reached baseline 288% (2.88 times) faster than
individuals who scored a 19 at this same time point. There were significant moderating
effects of stress on affective responses during exercise. Feeling (pleasure/displeasure),
activation (arousal), muscular pain and RPE (exertion) trajectories were moderated by
stress. Exploratory analyses found that stress moderated physical recovery, but not
psychological recovery in the first hour after the E-RES workout. Also, stress was related
to the increase in IL-1β, a pro-inflammatory cytokine, in the 48 hour period after exercise
for a sub-set of participants. These findings likely have important theoretical and clinical
implications for those undergoing vigorous physical activity. Those experiencing chronic
loads of stress and mental strain should include more rest time to ensure proper recovery.
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.
In this study, we pursue determining the effect of pentoxifylline (Ptx) in delayed-onset muscle soreness (DOMS) triggered by exposing untrained mice to intense acute swimming exercise (120 min), which, to our knowledge, has not been investigated. Ptx treatment (1.5, 4.5, and 13.5 mg/kg; i.p., 30 min before and 12 h after the session) reduced intense acute swimming–induced mechanical hyperalgesia in a dose-dependent manner. The selected dose of Ptx (4.5 mg/kg) inhibited recruitment of neutrophils to the muscle tissue, oxidative stress, and both pro- and anti-inflammatory cytokine production in the soleus muscle and spinal cord. Furthermore, Ptx treatment also reduced spinal cord glial cell activation. In conclusion, Ptx reduces pain by targeting peripheral and spinal cord mechanisms of DOMS.
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.