An initial bout of maximal eccentric exercise (MaxEC) confers protective effect against muscle damage such that the magnitude of muscle damage is attenuated when the same exercise is repeated by the same muscles (1–3). This is referred to as the repeated bout effect (RBE) and has been shown for the elbow flexors (EF) (1,4,5), knee flexors (KF) (6,7) and knee extensors (KE) (8–11), and tibialis anterior (12).
Several studies (2,13–15) have reported that the magnitude of muscle damage after MaxEC performed by the opposite homologous muscles is also attenuated, which is referred to as the contralateral RBE (CL-RBE). For instance, Chen et al. (2) showed that the CL-RBE was evident when the right and left EF MaxEC bouts were separated by 1 d (changes in muscle damage indices were reduced by 51% on average), 1 wk (48%), or 4 wk (26%), but not within 12 h or at 8 wk. For leg muscles, Hody et al. (16) found no CL-RBE when two MaxEC bouts of the KE were separated by 6 wk. However, Xin et al. (15) reported that the CL-RBE was evident when two MaxEC bouts of the KE were separated by 4 wk. It is possible that the profiles of the CL-RBE such as the magnitude of the effect and its duration are different between muscles.
Chen et al. (17) reported that muscle damage induced by maximal eccentric contractions was greater for the EF and elbow extensors than for the KF and KE, and greater muscle damage was evident for the KF than for the KE. The difference between the arm and leg muscles, and the two leg muscles was probably due to the difference in eccentric contractions performed by these muscles in daily activities (17). Hyldahl et al. (18) compared the magnitude of the RBE between MaxEC of the EF and the KE when the initial and secondary bouts were performed by the same muscles (not contralateral) with an interval of 2 wk, and found that the magnitude of the RBE was smaller for the KE than for the EF. Thus, it is possible that the profiles of the CL-RBE are also different between arm and leg muscles. However, no previous study has investigated the KF for the CL-RBE in comparison with its ipsilateral RBE (IL-RBE). We thought that the comparison between the KF and the EF would provide important information leading to the mechanisms underpinning the CL-RBE.
Therefore, the current study tested the hypothesis that CL-RBE of the KF would be observed at 1, 7, and 28 d after the initial eccentric exercise bout as shown in the EF. The present study also compared the magnitude of the RBE between the KF found in the present study and the EF reported in our previous study (2), to test the hypothesis that the magnitude of the CL-RBE would be smaller for the KF than for the EF.
Subjects and Study Design
Sedentary young men (n = 52) who were university students who had no musculoskeletal injuries of the lower extremities were recruited for this study. They provided informed consent to participate in this study, which had been approved by the institutional ethics review board. The study was conducted in conformity with the policy statement regarding the use of human subjects by the Declaration of Helsinki and Medicine & Science in Sports & Exercise®. Their mean ± SD age, height, body mass, and maximal voluntary isokinetic (60°·s−1) concentric contraction torque of the KF (MVC-KF torque) were 21.4 ± 1.8 y, 172.9 ± 4.8 cm, 63.7 ± 7.1 kg, and 68.9 ± 6.3 N·m, respectively.
The sample size was estimated using the data from our previous study in which the IL-RBE of the KF was investigated (19). On the basis of the possible effect size of 1 for the difference in some variables between bouts, an alpha level of 0.05, and a power (1 − β) of 0.80 (20), it was shown that at least 12 participants were necessary per group. The participants were placed into one of the four groups (n = 13 per group) by matching the baseline MVC-KF torque among the control and three experimental groups as much as possible. The experimental groups (1d, 7d, and 28d) performed the first bout of maximal eccentric contractions of the KF (MaxEC1) with a randomly chosen leg (either dominant or nondominant leg) followed by the second bout of MaxEC (MaxEC2) of the KF of the opposite leg (contralateral leg) 1, 7, or 28 d later, respectively. The choice of the dominant and nondominant legs was counterbalanced among the participants. The participants in the control group performed two bouts of MaxEC by their nondominant leg separated by 14 d on the basis of the previous study (2) in which the CL-RBE and IL-RBE of the EF were investigated. It should be noted that the changes in the muscle damage markers do not fully return to the baseline in 7 d (19); thus, the 7-d interval was not ideal for the control condition. It was possible to set the interval to 28 d, but to compare with the RBE of the EF, it was better to use the 14-d interval. No significant differences in age, height, body mass, and baseline values of all dependent valuables were observed among the groups (Table 1).
A familiarization session was set at 3 d before MaxEC1, in which the participants experienced measurements of muscle soreness and range of motion (ROM) and performed submaximal (approximately 50%) MVC-KF torque and MVC torque of the KE (MVC-KE torque) measures. The investigator demonstrated the MaxEC, but no eccentric contractions of the KF were performed by the participants.
All participants performed two bouts of 10 sets of six maximal eccentric contractions of the KF (MaxEC) on an isokinetic dynamometer (Biodex System 3 Pro; Biodex Medical Systems, Shirley, NY). The protocol of the KF eccentric exercise was based on our previous study (21). Briefly, each participant lay prone on the platform of the dynamometer, and the trunk and the unexercised leg were strapped to the platform. The knee joint of the exercise leg was forcibly extended from 90° flexion to a fully extended position (0°, full-knee extension angle) by the dynamometer at 30°·s−1, whereas each participant was asked to maximally resist against the knee extending motion (19,21). Each contraction lasted for 3 s and was repeated every 10 s, and a 2-min rest was given between sets. After each contraction, the isokinetic dynamometer passively brought the participant’s leg back to the knee (90°) at the angular velocity of 9°·s−1. The peak torque and work of each contraction were calculated using a software of the Biodex Medical Systems, and their average values of each set were used for further analysis (19,21).
The dependent variables consisted of MVC-KF torque, MVC-KE torque, ROM at the knee joint, plasma creatine kinase (CK) activity, and muscle soreness. MVC-KF and MVC-KE torques and ROM measures were taken 2 d and immediately before, immediately after, and 1, 2, 3, 4, and 5 d after MaxEC1 and MaxEC2 for all groups. Plasma CK activity and muscle soreness were measured at all time points shown previously except immediately after exercise. The test–retest reliability based on intraclass correlation coefficient (R) and coefficient of variation were 0.91 and 9.1% for MVC-KF, 0.92 and 0.98% for MVC-KE, 0.96 and 5.8% for ROM, 1.00 and 0.0% for muscle soreness, and 0.88 and 9.3% for plasma CK activity.
MVC-KF and MVC-KE torques
It has been reported that as few as two maximal voluntary isometric contractions at a long muscle length confer protective effect against muscle damage induced by maximal eccentric contractions performed several days later for the same muscle (22,23). To avoid a potential protective effect conferred by maximal voluntary isometric contraction torque measures, the present study used maximal voluntary “concentric” contraction torque to assess muscle function. Our previous study on the CL-RBE of the EF (2) also used maximal voluntary “concentric” contraction torque. MVC-KF and MVC-KE torques were measured by using the isokinetic dynamometer in the same participant position as that described for the MaxEC, at an angular velocity of 60°·s−1 for a ROM of 120° for the KF (0°–120°) and the KE (120°–0°) for three continuous contractions for both directions (19). MVC-KE torque measures were included to examine the effect of the eccentric exercise on the antagonist muscles. Verbal encouragement was provided during the tests. The highest value of the three trials for each of the KF and the KE torque was used for further analysis (24).
ROM was determined as the difference between the knee joint angles of maximal voluntarily flexion and extension measured by a manual goniometer. Three measurements were taken for each angle, and the mean of the three measurements was used to calculate ROM (19).
Plasma CK activity
Approximately 5 mL of venous blood was withdrawn from the cubital fossa region and centrifuged for 10 min to extract plasma by using a standard venipuncture technique, and plasma samples were stored at −80°C until analyses. Plasma CK activity was assayed spectrophotometrically by an automated clinical chemistry analyzer (Model 7080; Hitachi, Co Ltd, Tokyo, Japan) using a commercial test kit. Each sample was analyzed in duplicate, and the average value of two measures was used for further analysis.
Muscle soreness of the KF was quantified using a visual analog scale (VAS) that had a 100-mm continuous line, with “not sore at all” on one side (0 mm) and “very, very sore” on the other side (100 mm). The investigator asked the participant to rate his perceived soreness on the VAS when the muscles were passively extended (19).
Index of Protection
The magnitude of the protective effect (index of protection) was calculated using the values at 2 d after exercise for MVC-KF torque and ROM, and peak values for plasma CK activity and muscle soreness by the following equation: (MaxEC1 − MaxEC2)/MaxEC1 × 100 (2). If the responses were the same between MaxEC1 and MaxEC2, it was considered as no protection (the index is 0%), and if the index was 50%, it showed that the changes in the dependent variables were 50% smaller for the 2-d postexercise values of MVC-KF torque and ROM, or for the postexercise peak values of plasma CK activity and muscle soreness after MaxEC2 compared with MaxEC1.
To compare the magnitude of the RBE of the KF obtained from the present study with that of the EF, we used a part of the data from our previous study (2). In the study, untrained young men (similar to those used in the present study) performed exercise consisting of 30 (five sets of six) maximal isokinetic (30°·s−1) eccentric contractions of the EF for a ROM of 90° (90° elbow flexion to a full extension) with either a dominant or a nondominant arm followed by the same exercise using the opposite arm at 1, 7, or 28 d later. A control group used the nondominant arm for both bouts separated by 14 d. The study included comparable measures with those of the present study, such as MVC torque, ROM, plasma CK activity, and muscle soreness. Thus, the indices of protection for these parameters were compared for the matched conditions (i.e., control and the CL-RBE at 1, 7, and 28 d).
Data were assessed by using a Shapiro–Wilk test for the normality and a Levene test for the homogeneity of variance assumption. All dependent variables before each exercise bout were compared among the groups by a one-way ANOVA for each variable separately. Changes in peak torque and work between MaxEC1 and MaxEC2 over sets, and changes in the dependent variables (MVC-KF torque, ROM, CK, muscle soreness) over time were compared between MaxEC1 and MaxEC2 for each group by using a two-way (bouts–time) repeated-measures ANOVA. Changes in the variables after each MaxEC were compared among the groups by using a mixed-design, two-way ANOVA. When a significant interaction effect was found, a series of two-way ANOVA were performed to compare between two groups. When the ANOVA found a significant interaction effect, a Tukey’s post hoc test was performed. The index of protection for each muscle damage marker (MVC-KF torque, ROM, CK, muscle soreness) was compared among the groups (control, 1d, 7d, 28d) by using a one-way ANOVA. When the ANOVA found a significant main effect, a Tukey’s post hoc test was performed. The index of protection of each group (control, 1d, 7d, 28d) for each of the four muscle damage markers was also compared between the KF and the EF by using a t test. For all statistical analyses, a significant level was set at P ≤ 0.05. The data were presented as mean ± SD, unless otherwise stated.
No significant differences in any of the baseline-dependent variables existed among the groups before MaxEC1 (Table 1), and this was also the case for the baseline before MaxEC2 except plasma CK activity. Plasma CK activity was higher for the 1d group than for other groups before MaxEC2, because the 1d group performed MaxEC2 when plasma CK was still increased by MaxEC1.
The average peak torque of the KF during MaxEC was similar between MaxEC1 (72 ± 14 N·m) and MaxEC2 (76 ± 17 N·m) for all groups. The average total work was also similar between MaxEC1 (4878 ± 904 J) and MaxEC2 (4990 ± 1040 J).
Changes in the dependent variables
No significant changes in MVC-KE torque were observed, but other dependent variables showed significant (P < 0.05) changes after MaxEC1 without significant differences among the groups (Figs. 1–4). When comparing the changes in the variables between MaxEC1 and MaxEC2 for each group separately, the changes in MVC-KF torque (Fig. 1), ROM (Fig. 2), plasma CK activity (Fig. 3), and muscle soreness (Fig. 4) were significantly smaller after MaxEC2 than MaxEC1 for the control, 1d, and 7d groups, but not for the 28d group. No significant differences in the changes in these variables after MaxEC2 were evident between the 1d and 7d groups, but the changes were significantly larger for the 1d and 7d groups when compared with the control group (Figs. 1–4).
Index of protection
As shown in Table 2, the protective effect was greatest for the control group, and the average indices of protection for MVC-KF torque, ROM, muscle soreness, and CK were 66%, 68%, 67%, and 83%, respectively. The index of protection for MVC-KF torque was greater (P < 0.05) for the control group than for the 1d, 7d, and 28d groups, and for the 1d and 7d groups than for the 28d group (P < 0.05). As for ROM, the protective index of the control group was greater (P < 0.05) than that of the 7d and 28d groups, and the index was also greater (P < 0.05) for the 1d and 7d groups than for the 28d group. For CK, the protective index of the control group was greater (P < 0.05) than that of the 7d and 28d groups, and a significant difference was also evident between the 7d and 28d groups (P < 0.05). The protective index of muscle soreness was greater (P < 0.05) for the control than that for the 7d and 28d groups, and the 1d group was greater (P < 0.05) than the 28d group.
When compared between the KF and the EF for the matched groups (i.e., control, 1d, 7d, 28d), the indices of protection for MVC-KF and ROM were not significantly different (P > 0.05) between the KF and the EF for the 1d, 7d, 28d, and control groups (Table 2). Regarding the index of protection of CK, the KF was smaller (P < 0.05) than the EF for the control and 28d groups only. The index of protection for muscle soreness was smaller (P < 0.05) for the KF than the EF for the 28d group only.
The present study demonstrated that changes in all criterion measures after MaxEC2 were significantly smaller than those after MaxEC1 for the control group, which performed MaxEC2 with the same leg 14 d later, and also for the experimental groups, which performed MaxEC2 either at 1 or 7 d after MaxEC1 by the opposite leg (Figs. 1–4). These results suggest that the CL-RBE of the KF was evident for the interval of 1 and 7 d, but was lost between 7 and 28 d. This supported the hypothesis that the CL-RBE of the KF would be observed but rejected the hypothesis that the effect would last for 28 d as previously shown by the EF (2).
It is important to note that no significant changes in MVC-KE torque were evident after MaxEC1 and MaxEC2, indicating that muscle damage was induced to the KF only. The changes in MVC-KF torque, ROM, plasma CK activity, and muscle soreness after MaxEC1 were similar among the groups (Figs. 1–4) and were also similar to those reported in the previous studies in which a similar eccentric exercise of the KF was performed by non–resistance-trained individuals (7,19). The changes in the peak torque and work over sets were not significantly different between MaxEC1 and MaxEC2 for all groups; thus, it was assumed that the exercise was performed similarly between bouts and among the groups. The control group showed a typical RBE, which was similar to that reported in the previous studies examining the KF RBE (7,19). The changes in the dependent variables should have been similar between bouts, if no effects of MaxEC1 had been transferred to the opposite leg for the experimental groups. However, the 1d and 7d groups showed significantly smaller changes in and faster recovery of all variables after MaxEC2 when compared with those after MaxEC1 (Figs. 1–4), but the changes were not significantly different between bouts for the 28d group. This suggests that the CL-RBE was conferred for the 1d and 7d groups, but not for the 28d group. Previous studies had already found the CL-RBE for the EF (2,13,14), KE (15), and tibialis anterior muscle (12), but the present study was the first to show the CL-RBE of the KF.
As shown in Table 2, the magnitude of the protective effect on MVC-KF torque (42%), ROM (46%), plasma CK activity (62%), and muscle soreness (40%) in the 7d group seemed to be smaller than that of the control group, which repeated the second bout at 14 d after the initial bout with the same leg (MVC-KF torque, 66%; ROM, 68%; CK, 83%; muscle soreness, 67%). However, it should also be noted that the interval between bouts was longer for the control group (14 d) than for the 7d group. It would have been better to set the same interval between the control and the experimental groups; thus, having the different interval between bouts for the control and experiment groups was a limitation of the present study. However, it seems likely that the magnitude of the protective effect gradually decreased over time when the interval between bouts was increased from 7 to 28 d. Considering the difference in the magnitude of the protective effect between the 7d and 28d groups, it is assumed that the magnitude of the CL-RBE was approximately 50% of that of the IL-RBE for the same time interval such as 14 d.
It has been reported that the magnitude of the muscle damage is smaller for the KF than for the EF, which is probably because lower extremity muscles are more exposed to submaximal eccentric contractions in daily activities when compared with upper extremity muscles (17). As shown in Table 2, the magnitude of the CL-RBE of the KF and the EF was similar when the interval between bouts was 1 or 7 d, but when the interval between bouts was 28 d, the index of protection was smaller for the KF than for the EF. Hyldahl et al. (18) reported that the magnitude of the IL-RBE was smaller for the KE when compared with the EF, and speculated that this was associated with the less muscle damage induced after the initial bout for the KE than for the EF. It should be noted that the difference in the magnitude of the changes in the indirect muscle damage markers (e.g., MVC, CK, muscle soreness) between the KF and the EF was smaller than that between the KE and the EF, when 30 maximal eccentric contractions were performed for both exercises (18). It should be noted that the number of KF eccentric contractions was 60 in the present study, and Chen et al. (17) found that the magnitude of muscle damage after the first bout was greater for the KF than for the KE. This may explain the similar magnitude of not only the IL-RBE (control group) but also the CL-RBE (1d and 7d groups) between the KF and the EF demonstrated in the present study. It is interesting to investigate whether the magnitude of the CL-RBE for the interval of 28 d becomes similar, when the magnitude of muscle damage is matched between the KF and the EF. As shown previously, it seems that the magnitude of the CL-RBE is approximately 50% of that of the IL-RBE for the same interval for the same parameter. It seems possible that the greater the IL-RBE, the greater the CL-RBE; thus, the two types of the RBE are associated. Further study is warranted to confirm this.
Regarding the potential mechanisms, Hyldahl et al. (18) have documented that the RBE is a combination of neural adaptations, muscle–tendon complex behavior changes, extracellular matrix structural remodeling, and modified inflammatory responses. It seems reasonable to assume that the CL-RBE is more associated with neural adaptations than with adaptations at muscle fibers and extracellular matrix. It may be that the underlying mechanisms of the CL-RBE are somewhat similar to those of the cross-education effect in which resistance training of one limb increases muscle strength of the contralateral limb (25,26). A meta-analysis study showed that an average increase in strength of 52% in the trained limb was accompanied by a significant 7.6% increase in the untrained limb (27). However, when comparing the CL-RBE and the IL-RBE (Table 2), the cross-transfer effect seems greater for the CL-RBE (approximately 50% of the IL-RBE as discussed previously) than the cross-education effect on strength gain (e.g., 7.6%/52% × 100 = 15%). Interestingly, Kidgell et al. (28) showed that the extent of the cross-education effect on maximal voluntary isometric contraction strength of the wrist flexors was significantly greater after eccentric training (+47%) than after concentric training (+28%) performed three times a week for 4 wk. It is possible that the effects of eccentric contractions performed by one limb are transferred to the contralateral limb greater. Hendy and Lamon (29) have recently stated in their review article about cross-education phenomenon that functional reorganization of the motor cortex facilitates the effects of cross-education, and cross-activation of the “untrained” motor cortex (ipsilateral to the trained limb) by increased neural drive from the “untrained” motor cortex contributes to the cross-education effect. This may be applied to the mechanisms of the CL-RBE, at least partially.
It is also possible that neural adaptations lead to muscle–tendon behavior changes. Lau et al. (30) reported that the RBE of the same EF was associated with smaller displacement of biceps brachii myotendinous junction during the second bout than during the initial bout. For such muscle–tendon behavior changes to be produced, it seems reasonable to assume that muscle activation pattern is modified. As for modifications of inflammatory responses, it has been reported that brain cytokines (e.g., interleukin-1β) increase after downhill running in animal studies (31,32), suggesting that inflammatory responses could also affect the central nervous system. Interestingly, Xin et al. (15) reported that an increase in inflammatory-related transcription factor nuclear factor kappa–light-chain-enhancer of activated B cells (NF-κB) in vastus lateralis after MaxEC of the KE was attenuated in the contralateral leg after the second exercise bout (109.1% ± 3.0%) when compared with the initial bout performed by the opposite leg (122.9% ± 2.6%). They concluded that the CL-RBE could be due to the attenuated increase in NF-κB activity after exercise and speculated that NF-κB might be an effector of an upstream mechanistic pathway that could be transferred to the nonexercising contralateral leg muscles. It is also interesting that Xin et al. (15) showed that the CL-RBE of the KE lasted for 4 wk, but the present study did not find evidence of the CL-RBE at 28 d. It should be noted that the participants in the study by Xin et al. (15) took antioxidant and anti-inflammatory supplements before the first eccentric exercise bout. This may have affected the length of the CL-RBE. If a circulating factor is involved, one might expect that other muscles might demonstrate less muscle damage than not just the homologous contralateral muscle. Further studies are needed to investigate the protective effect of a lower limb muscle eccentric exercise on an upper limb muscle eccentric exercise, and vise versa, and the protective effect of one muscle on its antagonist muscle in the upper or lower limb.
The current study provides some potential clinical implications. When muscles are disused for a while such as after a long-term immobilization, the muscles become more susceptible to eccentric exercise–induced muscle damage. The fact that the muscle damage of the KF of one leg was attenuated after performing maximal eccentric contractions of the KF of the other leg as shown in the present study (Figs. 1–4) may suggest that it is possible to attenuate the magnitude of muscle damage by starting eccentric exercise with a nonimmobilized leg. Hamstrings are the most frequently injured muscles in sporting activities (33,34), so it is likely that its use is restricted for some time. If one of the hamstrings is not used for a while, it is recommended that before retraining of the injured hamstrings, eccentric exercise can be given to the contralateral un-injured hamstrings to minimize potential muscle damage that could occur when the immobilized muscles undergo eccentric contractions.
In summary, the current study demonstrated that the CL-RBE was evident for the KF, and it lasted for 7 d but not for 28 d. The magnitude of the CL-RBE on indirect muscle damage markers seems to be similar between the KF and the EF, but the CL-RBE of the KF seems to last shorter than that of the EF. Further studies are warranted to investigate the mechanisms underpinning the CL-RBE, and it is interesting to investigate whether the protective effects against muscle damage could be transferred from arm to leg muscles, or vise versa. It did not seem that the KE was affected by the KF eccentric exercise as shown by no significant decreases in MVC-KE torque after the exercise (Table 1). However, it is not known whether eccentric exercise can confer protective effect on an antagonist muscle of the ipsilateral and contralateral limbs. This also warrants further investigation.
The authors thanks Miss Jui-Hsin Lin for her assistance with the data collection.
This work was supported by the Ministry of Science and Technology (MOST 102-2628-H-415-036-MY3 and 105-2410-H-003-052-MY3), Taiwan.
The authors declare that they have no conflict of interest. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.
1. Chen TC, Nosaka K, Sacco P. Intensity of eccentric exercise, shift of optimum angle, and the magnitude of repeated-bout effect. J Appl Physiol (1985)
2. Chen TC, Chen HL, Lin MJ, Yu HI, Nosaka K. Contralateral repeated bout effect of eccentric exercise of the elbow flexors. Med Sci Sports Exerc
3. 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
4. Chen TC, Chen HL, Liu YC, Nosaka K. Eccentric exercise-induced muscle damage
of pre-adolescent and adolescent boys in comparison to young men. Eur J Appl Physiol
5. Chapman DW, Newton MJ, McGuigan MR, Nosaka K. Effect of slow velocity lengthening contractions on muscle damage
induced by fast-velocity lengthening contractions. J Strength Cond Res
6. Nikolaidis MG, Paschalis V, Giakas G, et al. Favorable and prolonged changes in blood lipid profile after muscle-damaging exercise. Med Sci Sports Exerc
7. Paschalis V, Nikolaidis MG, Giakas G, Jamurtas AZ, Owolabi EO, Koutedakis Y. Position sense and reaction angle after eccentric exercise: the repeated bout effect. Eur J Appl Physiol
8. Black CD, McCully KK. Muscle injury after repeated bouts of voluntary and electrically stimulated exercise. Med Sci Sports Exerc
9. Deyhle MR, Gier AM, Evans KC, et al. Skeletal muscle inflammation following repeated bouts of lengthening contractions in humans. Front Physiol
10. Hyldahl RD, Nelson B, Xin L, et al. Extracellular matrix remodeling and its contribution to protective adaptation following lengthening contractions in human muscle. FASEB J
11. Paschalis V, Theodorou AA, Panayiotou G, et al. Stair descending exercise using a novel automatic escalator: effects on muscle performance and health-related parameters. PLoS One
12. Hosseinzadeh M, Samani A, Andersen OK, Nosaka K, Arendt-Nielsen L, Madeleine P. Ipsilateral resistance exercise prevents exercise-induced central sensitization in the contralateral limb: a randomized controlled trial. Eur J Appl Physiol
13. Howatson G, van Someren KA. Evidence of a contralateral repeated bout effect after maximal eccentric contractions. Eur J Appl Physiol
14. Starbuck C, Eston RG. Exercise-induced muscle damage
and the repeated bout effect: evidence for cross transfer. Eur J Appl Physiol
15. Xin L, Hyldahl RD, Chipkin SR, Clarkson PM. A contralateral repeated bout effect attenuates induction of NF-κB DNA binding following eccentric exercise. J Appl Physiol (1985)
16. Hody S, Rogister B, Leprince P, Laglaine T, Croisier JL. The susceptibility of the knee extensors to eccentric exercise–induced muscle damage
is not affected by leg dominance but by exercise order. Clin Physiol Funct Imaging
17. Chen TC, Lin KY, Chen HL, Lin MJ, Nosaka K. Comparison in eccentric exercise–induced muscle damage
among four limb muscles. Eur J Appl Physiol
18. Hyldahl RD, Chen TC, Nosaka K. Mechanisms and mediators of the skeletal muscle repeated bout effect. Exer Sports Sci Rev
19. Lin MJ, Chen TC, Chen HL, Liu YC, Nosaka K. Low-intensity eccentric contractions of the knee extensors and flexors protect against muscle damage
. Appl Physiol Nutr Metab
20. Cohen J. Statistical Power Analysis for the Behavioral Sciences
. 2nd ed. Hillsdale (NJ): Lawrence Erlbaum Associates; 1988. pp. 55–7.
21. Chen CH, Nosaka K, Chen HL, Lin MJ, Tseng KW, Chen TC. Effects of flexibility training on eccentric exercise–induced muscle damage
. Med Sci Sports Exerc
22. Chen HL, Nosaka K, Pearce AJ, Chen TC. Two maximal isometric contractions attenuate the magnitude of eccentric exercise–induced muscle damage
. Appl Physiol Nutr Metab
23. Chen TC, Chen HL, Lin MJ, Chen CH, Pearce AJ, Nosaka K. Effect of two maximal isometric contractions on eccentric exercise–induced muscle damage
of the elbow flexors. Eur J Appl Physiol
24. Tseng KW, Tseng WC, Lin MJ, Chen HL, Nosaka K, Chen TC. Protective effect
by maximal isometric contractions against maximal eccentric exercise–induced muscle damage
of the knee extensors. Res Sports Med
25. Farthing JP. Cross-education of strength depends on limb dominance: implications for theory and application. Exerc Sport Sci Rev
26. Hortobágyi T, Lambert NJ, Hill JP. Greater cross education following training with muscle lengthening than shortening. Med Sci Sports Exerc
27. Carroll TJ, Herbert RD, Munn J, Lee M, Gandevia SC. Contralateral effects of unilateral strength training: evidence and possible mechanisms. J Appl Physiol (1985)
28. Kidgell DJ, Frazer AK, Daly RM, et al. Increased cross-education of muscle strength and reduced corticospinal inhibition following eccentric strength training. Neurosci
29. Hendy AM, Lamon S. The cross-education phenomenon: brain and beyond. Front Physiol
30. Lau WY, Blazevich AJ, Newton MJ, Nosaka K. Reduced muscle lengthening during eccentric contractions as a mechanism underpinning the repeated-bout effect. Am J Physiol Regul Integr Comp Physiol
31. Carmichael MD, Davis JM, Murphy EA, et al. Role of brain IL-1beta on fatigue after exercise-induced muscle damage
. Am J Physiol Regul Integr Comp Physiol
32. de Rivero Vaccari JP, Dietrich WD, Keane RW. Therapeutics targeting the inflammasome after central nervous system injury. Transl Res
33. Kujala UM, Orava S, Jarvinen M. Hamstring injuries: current trends in treatment and prevention. Sports Med
34. Schmitt B, Tyler T, McHugh M. Hamstring injury rehabilitation and prevention of reinjury using lengthened state eccentric training: a new concept. Int J Sports Phys Ther