The purpose of this study was to use paired-pulse transcranial magnetic stimulation (TMS) to examine the effect of eccentric exercise on short-interval intracortical inhibition (SICI) after damage to elbow flexor muscles. Nine young (22.5 ± 0.6 yr; mean ± SD) male subjects performed maximal eccentric exercise of the elbow flexor muscles until maximal voluntary contraction (MVC) force was reduced by ∼40%. TMS was performed before, 2 h after, and 2 days after exercise under Rest and Active (5% MVC) conditions with motor-evoked potentials (MEPs) recorded from the biceps brachii (BB) muscle. Peripheral electrical stimulation of the brachial plexus was used to assess maximal M-waves, and paired-pulse TMS with a 3-ms interstimulus interval was used to assess changes in SICI at each time point. The eccentric exercise resulted in a 34% decline in strength (P < 0.001), a 41% decline in resting M-wave (P = 0.01), changes in resting elbow joint angle (10°, P < 0.001), and a shift in the optimal elbow joint angle for force production (18°, P < 0.05) 2 h after exercise. This was accompanied by impaired muscle strength (27%, P < 0.001) and increased muscle soreness (P < 0.001) 2 days after exercise, which is indicative of muscle damage. When the test MEP amplitudes were matched between sessions, we found that SICI was reduced by 27% in resting and 23% in active BB muscle 2 h after exercise. SICI recovered 2 days after exercise when muscle pain and soreness were present, suggesting that delayed onset muscle soreness from eccentric exercise does not influence SICI. The change in SICI observed 2 h after exercise suggests that eccentric muscle damage has widespread effects throughout the motor system that likely includes changes in motor cortex.
- motor control
- motor cortex
unaccustomed eccentric exercise involving the repetitive lengthening of muscle is known to cause significant damage to the ultrastructural and cytoskeletal components of muscle fibers (1) and an impairment in the excitation-contraction coupling process (59). The consequences of this exercise-induced muscle damage are a long-lasting decline in muscle strength, a shift in the optimal muscle length for force generation, muscle swelling, and an increase in passive muscle tension or stiffness (46). Furthermore, muscle pain develops 1 or 2 days after the exercise, which is thought to reflect increased release of noxious chemicals from damaged muscle (39). This delayed onset muscle soreness (DOMS) is not discernible at rest but is elicited under mechanical stimulation such as pressure, stretching, or contraction of the affected muscle (45), which can produce debilitating and long-lasting effects on muscle function (7).
Along with these changes in the muscle, several lines of evidence suggest that eccentric muscle damage produces changes in the central nervous system, such as a disturbance in proprioception (3, 6, 60), reduced maximal activation of muscle (44), alterations in the electromyogram (EMG)-force relationship and increased force fluctuations (54, 60), and an increase in antagonist muscle coactivation (30, 54, 56). More recently, we have used single motor-unit recordings in elbow flexor muscles to show that eccentric muscle damage alters the neural control of spinal motor neurons, as shown by an increase in mean motor-unit discharge rates, a decrease in motor-unit recruitment thresholds, and an increase in motor-unit synchronization (13, 14), the latter of which can last for at least 7 days after the exercise (12). However, it is not currently known whether these central effects of muscle damage are isolated to changes at the spinal level or also manifest as changes in the cortical control of muscle force that involve the motor cortex.
Transcranial magnetic stimulation (TMS) of the motor cortex is a noninvasive technique that allows quantitative assessment of corticospinal activity in humans. Descending volleys elicited by TMS arrive at motor neurons and evoke a response in muscles that is recorded with surface EMG electrodes. Because the size of this motor-evoked potential (MEP) depends on the level of excitation of motor cortex and spinal motor neurons, it is not possible to ascribe any change in the MEP following single-pulse TMS to changes in cortical or spinal excitability. In contrast, intracortical inhibition in human motor cortex can be studied with paired-pulse TMS, where a first-conditioning TMS, which is subthreshold for a motor response, activates an intracortical inhibitory circuit, reducing the size of the MEP elicited by a second suprathreshold test TMS pulse, delivered up to 5 ms later (28). This phenomenon is termed short-interval intracortical inhibition (SICI), and there is considerable evidence to show that SICI involves a GABAA circuit (62) and is mediated at cortical rather than subcortical structures (17, 28).
GABAergic inhibitory systems responsible for SICI are crucial in modulating corticospinal output, with increasing evidence suggesting that SICI plays an important role in motor performance. For example, SICI effects on corticospinal excitability are suppressed during voluntary activation (48), and the modulation of SICI is likely to be important for activating the desired combination of muscles for the task (63). The importance of SICI in motor performance is also highlighted by the increased prevalence of abnormal SICI in several movement disorders (2). Reductions in SICI are also observed following interventions that modulate motor performance, such as motor training (8, 40), fatigue (33, 57), and immobilization (61). However, the effect of muscle damage from eccentric exercise on SICI, which is known to impair motor performance (5, 54), is unknown. Furthermore, previous studies have shown differences in intracortical inhibition that are dependent on the activity state of the muscle (9, 35); so, we wanted to examine SICI after eccentric muscle damage at rest and during muscle activation, particularly as DOMS is greatest during muscle activation. Based on other interventions that modulate SICI and impair motor performance (33, 57, 61), we hypothesize that muscle damage from eccentric exercise will result in reduced SICI at rest or during muscle activation.
Nine young (22.5 ± 0.6 yr; mean ± SD), neurologically healthy male subjects gave written, informed consent to participate in this study. All procedures conformed to the Declaration of Helsinki and were approved by the Human Research Ethics Committee at The University of Adelaide.
All subjects underwent three experimental sessions, which were performed before, 2 h after, and 2 days after a bout of eccentric exercise to induce muscle damage of the left (nondominant) arm. The experimental procedure was replicated in each of these sessions and involved elbow flexion tasks, electrical stimulation of the brachial plexus, and TMS. The session 2 h after eccentric exercise was performed to examine the changes in intracortical inhibition after eccentric exercise in the presumed absence of metabolic fatigue, as we have shown previously that a similar decline in maximal strength recovers within 2 h following concentric but not eccentric exercise (18). The session 2 days after eccentric exercise coincided with the peak in DOMS (44).
For each experimental session, subjects were seated in an experimental chair with the elbow joint of the left arm at 90° flexion. The subject's forearm was supinated and secured vertically in the manipulandum by two wide nylon straps. A force transducer (range 0-670 N; model MLP-150; Transducer Techniques, Temecula, CA), located perpendicular to the forearm at the level of the wrist, measured isometric elbow flexion force in the sagittal plane. During experiments, subjects underwent procedures to assess muscle strength, M-waves, and TMS, while the target arm muscles were relaxed (Rest condition) and while maintaining an isometric flexion contraction at 5% of the maximal voluntary contraction (MVC) strength obtained in that session (Active condition).
Surface EMG signals were recorded with pediatric (3.2-cm diameter) self-adhesive, disposable surface electrodes (3M Red Dot; 3M, Ontario, Canada), placed on the skin over the distal tendon and muscle belly of biceps brachii (BB) muscle. A grounding strap was fastened around the proximal part of the arm (just above the elbow), and the EMG signal was displayed on an oscilloscope for subject feedback. After the first experimental session, the electrodes were removed and their positions marked on the skin for correct placement for subsequent sessions. The EMG was amplified (100–1000×), bandpass filtered (20–1,000 Hz), and digitized (2,000 Hz) using a CED 1401 interface and 1902 amplifier (Cambridge Electronic Design, UK).
Relaxed elbow angle.
The resting elbow joint angle was assessed before each experimental session as an indicator of the passive tension in the elbow flexor muscles. Three landmarks were marked on the arm with indelible ink, while the subjects stood relaxed with their arms hanging by their side. These landmarks consisted of the midpoint of the acromion and coracoid process, the lateral epicondyle of the humerus, and the midpoint of the ulnar and radius styloid processes. A goniometer was lined up to these landmarks, and the resting elbow angle was recorded.
Subjects performed two tasks to measure elbow flexor strength: one in the experimental apparatus to measure maximal isometric flexion force and one on an isokinetic dynamometer (Biodex System 4; Biodex, Shirley, NY) to measure maximal concentric torque. All muscle-strength measurements (force or torque) were digitized at 200 Hz with a Cambridge Electronic Design interface and Spike2 software. For the isometric MVC task, subjects performed a 3-s ramp contraction (zero to maximum) in the flexion direction and then maintained the contraction for a further 3 s, while receiving strong verbal encouragement. Subjects performed three trials, which were each separated by a 1-min rest, and the largest force was designated as the MVC force. After each contraction, subjects were asked to rate the extent of muscle pain that was felt during the contraction by placing a mark on a 10-cm visual analog scale (VAS) showing “no pain” at the left extreme and “excruciating pain” at the right extreme. To measure concentric MVC torque, subjects were seated at an isokinetic dynamometer and performed three maximal concentric contractions at 60°/s over the full range of motion for the elbow joint. These data were averaged over 12° increments from 32° to 140° of elbow flexion (nine bins). Fourth-order polynomials were then fitted to these data points in Matlab (MathWorks, Natick, MA) to obtain peak torque and optimal elbow joint angle during the concentric contractions (4).
While positioned in the experimental apparatus, single rectangular pulses (200-μs duration) were delivered via a DS7AH constant current stimulator (Digitimer, UK) to the brachial plexus at Erb's point to assess maximal compound muscle action potentials for the BB muscle. The cathode was placed in the supraclavicular fossa and the anode over the acromion. Stimulus intensity was increased until responses had plateaued. This stimulus intensity was then exceeded by 20% (supramaximal) to obtain the maximal M-wave (M-max). M-wave peak-to-peak amplitudes were analyzed offline using the Signal 4.0 Signal Analysis system.
TMS was delivered with two Magstim 200 stimulators (Magstim, UK), connected with a BiStim module (Magstim) to allow the output of both stimulators to be discharged through a single circular coil (90-mm diameter). The coil was held on the scalp near the vertex to produce posterior-anterior current flow in the right motor cortex. The optimal site for eliciting a MEP in the relaxed BB muscle was identified and marked on the scalp with an indelible ink pen. Coil position and orientation were checked constantly during the experiment to ensure that no changes occurred.
TMS thresholds were defined according to international guidelines (50, 51), as described previously (24). Resting motor threshold was defined as the minimum stimulus intensity for eliciting MEPs of >50 μV peak-to-peak amplitude in at least five of 10 consecutive trials in the relaxed BB muscle. Active motor threshold (AMT) was defined as the lowest stimulus intensity required to produce MEPs of at least 200 μV amplitude in at least five of 10 consecutive trials, while the BB muscle was activated at 5% of the MVC force. Stimulus intensity was adjusted by 1% of maximum stimulator output (MSO) to determine these thresholds. MEP peak-to-peak amplitudes were obtained online using Signal 4.0 Signal Analysis software.
Paired-pulse TMS involving a subthreshold conditioning stimulus at 70%, 80%, or 90% of AMT, followed 3 ms later by a suprathreshold test stimulus, was used to assess intracortical inhibition (28). Trials were assessed for Rest and Active conditions using a test TMS intensity set to produce a MEP of ∼0.5 mV in the relaxed BB muscle. Active trials using a reduced test TMS intensity (ActiveRI), adjusted to produce an ∼0.5-mV MEP in BB muscle during a 5% MVC, were also performed. Each data block consisted of 10 trials at each conditioning intensity and 10 test-alone trials, delivered in random order (40 pulses). SICI was assessed by measuring the peak-to-peak MEP amplitude of each trial and normalizing the mean MEP amplitude in the conditioned trials to the mean MEP amplitude in the test-alone trials to obtain a value relative to 100%. Values <100% indicate that the conditioning TMS reduced the size of the test TMS through intracortical inhibitory circuits.
Following the first experimental session, subjects performed controlled eccentric exercise of the left elbow flexor muscles on an isokinetic dynamometer (Biodex System 4; Biodex). Subjects were seated and positioned to perform eccentric contractions at 45°/s from 90° flexion to full elbow extension, as performed previously (12). Each muscle contraction lasted 2 s, followed by a 4-s rest period in which the subjects relaxed while the dynamometer arm returned automatically back to 90° of elbow flexion to begin the next repetition. Contractions were performed in sets of 10 with 30 s rest between sets. Isometric muscle strength at 90° of elbow flexion was measured on the isokinetic dynamometer after 30 contractions and regularly tested until muscle strength was reduced by 40% (12). A constant reduction in strength was used to obtain a putatively similar extent of muscle damage in all subjects, which reduces the variability in strength loss after eccentric exercise compared with protocols that use a set number of contractions in all subjects.
A one-way repeated-measures ANOVA was used to assess changes in MVC force, resting elbow joint angle, muscle soreness, and optimal elbow joint angle between Exercise sessions (before, 2 h after, and 2 days after exercise). A two-way repeated-measures ANOVA comparing Activity State (Rest and Active) with Exercise (before, 2 h after, and 2 days after exercise) was performed for TMS thresholds, test-alone MEP amplitudes, and TMS intensities. SICI was analyzed by a three-way repeated-measures ANOVA comparing Activity State (Rest, Active, and ActiveRI), Conditioning Intensity (70%, 80%, and 90% AMT), and Exercise. Fisher post hoc test was used to analyze the significant main effect and its interactions. Statistical significance was set at P ≤ 0.05 for all comparisons. Data are provided as mean ± SE unless indicated otherwise.
From 40 to 180 eccentric contractions were required to obtain a reduction in maximal elbow flexor muscle torque of at least 40% in all nine participants. The indicators of muscle damage, as revealed by changes in muscle strength, optimal angle for force generation, muscle soreness, and relaxed elbow angle before and after eccentric exercise, are shown in Fig. 1. When tested in the experimental apparatus, MVC force (Fig. 1A) was 34% lower (P < 0.001) 2 h after and 27% lower (P < 0.001) 2 days after exercise compared with before exercise. The optimal elbow joint angle for maximum torque production had shifted to longer muscle lengths by 18° 2 h after exercise (Fig. 1B; P < 0.05) and remained shifted (19°) 2 days after exercise (P < 0.05) compared with before exercise. Muscle soreness (Fig. 1C), ranging from zero to 10 points on a VAS, was not significantly different before and 2 h after exercise (P = 0.75) but was increased significantly 2 days later (P < 0.001 compared with before exercise). Furthermore, relaxed elbow joint angle (Fig. 1D) was reduced by 10° 2 h after (P < 0.001) and remained reduced (8°, P < 0.001) 2 days after exercise compared with before exercise.
M-max was altered after eccentric exercise (Exercise effect, P = 0.004) but did not differ between Rest and Active conditions (Activity State effect, P = 0.97). M-max for BB at rest was significantly lower 2 h after exercise (11.9 ± 1.9 mV) compared with before exercise (20.3 ± 2.6 mV, P = 0.01), which had recovered 2 days later (20.5 ± 2.2 mV, P = 0.86). Similarly, M-max for BB, when the muscle was active, was significantly lower 2 h after exercise (12.0 ± 1.9 mV) compared with before (21.1 ± 2.3 mV, P = 0.006) and 2 days after exercise (20.5 ± 2.3 mV, P = 0.01).
Paired-Pulse TMS and Eccentric Exercise
A representative example of M-max and MEP responses from paired-pulse TMS in one subject obtained before and after eccentric exercise is shown in Fig. 2. In this subject, there was a 53% decline in M-wave amplitude 2 h after exercise, which had recovered 2 days later (Fig. 2A). For the assessment of SICI, the test-alone TMS intensity was adjusted to produce a test MEP of similar amplitude in all three sessions (∼0.7 mV), which for this subject, required a TMS intensity of 51% MSO before exercise and 49% MSO 2 h and 2 days after exercise. Paired-pulse TMS (Fig. 2B) was obtained at conditioning intensities of 70%, 80%, and 90% of AMT and normalized to the mean test-alone MEP performed in the same block of trials. Although there was within-subject variability among the different conditioning intensities, the magnitude of SICI in the active muscle when pooled over all conditioning intensities was reduced (average SICI of 50%) 2 h after exercise compared with before exercise (average SICI of 40%) in this subject.
For all subjects, the test-alone TMS intensities were set to produce an ∼0.5-mV MEP in resting BB muscle in each experimental session. The same test TMS intensity was used for the test-alone MEP in the active muscle, and the test TMS intensity was also reduced (ActiveRI) to match the ∼0.5-mV test-alone MEP in the relaxed muscle. The test-alone TMS intensities were 70 ± 3% MSO in the Rest and Active conditions and 51 ± 2% MSO in the ActiveRI condition (P < 0.001). These TMS intensities were not influenced by Exercise (P = 0.08). For the Rest and Active conditions, the test TMS intensities were 68 ± 4% MSO before exercise, 74 ± 5% MSO 2 h after exercise, and 69 ± 5% 2 days after exercise. For the ActiveRI condition, the test TMS intensities were 50 ± 3% MSO before exercise, 52 ± 3% MSO 2 h after exercise, and 52 ± 2% MSO 2 days later.
The test-alone MEP amplitudes that were used to quantify SICI in BB muscle are shown in Fig. 3A. As expected, there was a significant increase in test-alone MEP amplitude when the muscle was Active compared with the Rest (P < 0.001) and ActiveRI conditions (P < 0.001). When normalized to the M-max, the test-alone MEPs were different between exercise sessions (P < 0.001) and activity states (P < 0.001), and there was an exercise × activity state interaction (P = 0.006). Subsequent post hoc analysis showed that in resting muscle, there was no significant difference between the normalized test-alone MEP 2 h after exercise (6.3 ± 1.3% M-max) compared with before (2.5 ± 0.5% M-max, P = 0.16) and 2 days after exercise (3.8 ± 0.7% M-max, P = 0.4). Furthermore, in the ActiveRI, there was no significant difference in the normalized test-alone MEP 2 h after exercise (7.1 ± 1.6% M-max) compared with before (3.2 ± 0.5% M-max, P = 0.15) and 2 days after exercise (3.3 ± 0.4% M-max, P = 0.16). In contrast, the normalized test-alone MEP was significantly greater 2 h after exercise (25.0 ± 3.6% M-max) compared with before (12.8 ± 2.5% M-max, P < 0.001) and 2 days later (13.0 ± 2.7% M-max, P < 0.001).
SICI for control of the BB muscle obtained before, 2 h after, and 2 days after exercise is shown in Fig. 3B. These data are shown pooled for conditioning intensities, as there was no significant effect of conditioning intensity in the ANOVA (P = 0.78) and no significant interactions. However, SICI was influenced by Exercise (P = 0.04), and there was reduced inhibition during muscle activation (P < 0.001). In resting BB muscle, there was a 27% reduction in SICI 2 h after exercise compared with before exercise (P = 0.05), which returned to pre-exercise levels 2 days later. Similarly, in the active BB muscle, there was a 23% reduction in SICI 2 h after exercise compared with before exercise (P = 0.02). However, there was no effect of exercise on SICI in the active BB muscle when the test-alone MEP was reduced to match the MEP obtained at rest (ActiveRI, P = 0.27).
The present study investigated the effect of eccentric exercise of elbow flexor muscles on intracortical inhibition after muscle damage. We found that intracortical inhibition in the BB muscle was reduced 2 h after exercise, but this had recovered 2 days later even though DOMS was present at this time. These findings provide the first evidence of altered motor cortical excitability after eccentric muscle damage and suggest that intracortical inhibition recovers rapidly and is not influenced by DOMS.
Muscle Damage and Neuromotor Performance After Eccentric Exercise
We have used several indirect measures of muscle function suggesting that eccentric exercise resulted in significant damage to muscle fibers. These changes include a prolonged decline in muscle strength, a shift in the optimal joint angle to produce peak torque to longer muscle lengths, changes in the relaxed elbow joint angle that are indicative of increased passive muscle tension, and an increase in muscle soreness 2 days after the exercise. Changes in these and other markers of muscle damage are not observed after concentric exercise, which produces a short-lasting decline in muscle strength with minimal muscle damage (10, 18, 55). The decline in muscle strength after concentric exercise primarily results from metabolic fatigue in the muscle (19) with recovery of strength within 2 h (18, 26, 38). In contrast, muscle strength after eccentric exercise can take 1 wk or more to recover (11) and is considered to be one of the most reliable indicators of muscle damage in humans (58). Therefore, the changes in muscle function that we have observed after eccentric exercise are likely to result from damage to the ultrastructural and cytoskeletal components of muscle fibers (11).
Changes in sarcolemmal excitability, as shown by a change in the M-max, are a common occurrence after fatiguing exercise (21), which may lead to a failure in the generation and propagation of the action potential to the contractile apparatus. However, the effects observed after eccentric muscle damage of the elbow flexor muscles are inconsistent. For example, BB M-wave amplitude following motor-point stimulation was significantly lower immediately after (42) and 2 h after eccentric exercise (41). In contrast, other studies with brachial plexus stimulation (44) and musculocutaneous nerve stimulation (22) have shown no change in BB M-waves immediately after eccentric exercise. From these studies, it is tempting to speculate that the procedure used to measure the M-wave may be responsible for the discrepant findings. However, we used brachial plexus stimulation and found that the M-wave was reduced by ∼40% 2 h after eccentric exercise, which had recovered 2 days later. It is not readily apparent why we found a decline in the M-wave after eccentric exercise, whereas Prasartwuth et al. (44) did not, as both studies used brachial plexus stimulation and produced an equivalent decline in muscle strength after exercise, although the technique used to induce muscle damage was different between the two studies. Nonetheless, the reduced M-wave 2 h after eccentric exercise suggests that there was an impairment of sarcolemmal function observed in the present study. This could be explained by a disturbance of ion concentrations as a result of changes in ion permeability from the damaged sarcolemma (36, 42) or the activation of stretch-sensitive Na+ and Ca2+ channels as a result of the eccentric exercise (34).
Reduced Intracortical Inhibition After Eccentric Exercise
The paired-pulse technique used in the present study to assess intracortical inhibition involves a weak conditioning TMS that does not produce a descending volley in the corticospinal tract (17) or alter spinal H-reflexes (28), so the effects of subthreshold conditioning are mediated at a cortical level. The intracortical inhibitory neurons activated by the conditioning stimulus do not activate corticospinal neurons directly but act indirectly by inhibiting interneurons that are primarily responsible for late indirect (I)-waves (known as I3-waves) in corticospinal cells (17, 23). In support of previous studies in hand muscles (48, 63), we found reduced SICI in the active BB muscle (Fig. 2), which is thought to occur because there is an increased contribution of early I-waves (known as I1-waves) in the active state (23, 63), and these are not affected by SICI. Furthermore, the effect of SICI in the active BB muscle was reduced further with weaker test TMS (ActiveRI condition), which reflects a greater preferential activation of I1- and direct-waves in corticospinal neurons at low TMS intensities (15, 16).
Paired-pulse TMS in resting and active muscle was used to examine the changes in SICI after eccentric muscle damage. We show that there was a reduction in SICI of ∼25% in resting and active BB muscle after eccentric exercise, which returned to baseline levels 2 days later. No effect of eccentric muscle damage on SICI was observed in the active BB muscle with an ActiveRI, which involves a reduced contribution from I3-waves to the MEP (15, 16). These data suggest that the reduced SICI observed in resting and active muscle at the higher TMS intensity occurs due to a reduced excitability of intracortical inhibitory neurons responsible for I3-wave activation after eccentric muscle damage.
In the present study, we chose to use a constant test MEP amplitude between testing sessions, because it is known that SICI is influenced by the test MEP amplitude (49, 52). This approach is consistent with previous studies that have assessed SICI before and after an intervention that alters motor performance and is likely to involve a change in M-max, such as after fatigue (33) or immobilization (61). However, we found a significant reduction in M-wave 2 h after eccentric exercise, which may influence the estimate of SICI under some circumstances (29). In our study, we found that the normalized test MEP changed from 3% (before exercise) to 6% (2 h after) M-max at rest and from 13% to 25% M-Max in the active state. According to the findings of Lackmy and Marchand-Pauvert (29) (see their Fig. 4E), our differences between normalized MEPs before and after exercise in the resting muscle fall within a single pooled cohort of their samples (i.e., 0–10% M-max), where a 3% difference in normalized MEP is unlikely to have any discernable effect on SICI after exercise. Furthermore, they also show that the magnitude of SICI is similar for normalized test MEPs between 10% and 30% M-Max (29), which encompasses the range of values that we observed before and after exercise in the active muscle. These findings suggest that the change in M-wave, which we observed after eccentric exercise, was unlikely to have any effect on the assessment of SICI in the present study.
Although the factors that contribute to the reduced SICI after muscle damage are unknown, our experimental design suggests that it is unlikely to be due to muscle fatigue. We deliberately delayed the testing session for 2 h after eccentric exercise, because it has been shown previously that a decline in maximal strength from concentric exercise recovers within 2 h, whereas a similar decline in strength in the same subjects after eccentric exercise does not (18), suggesting that the decline in strength 2 h after eccentric exercise is due to muscle damage and not due to metabolic fatigue. Furthermore, we are confident that the reduced SICI that we observed 2 h after eccentric exercise is not due to fatigue, because the reduced SICI that occurs after fatiguing contractions recovers within 10–20 min after exercise (33, 57). Although low-frequency fatigue may still be present 2 h after eccentric exercise (18), this represents an impairment in the excitation-contraction coupling process that occurs in the absence of any metabolic disturbance within the muscle (25), so it is unlikely to have any effect on intracortical inhibition. It is also important to note that low-frequency fatigue would be present for many hours after fatiguing isometric contractions (19), but there is no long-lasting effect on SICI under these circumstances (33, 57), suggesting that these two phenomena are not related. In addition, we do not expect that the reduced SICI 2 h after exercise was influenced by DOMS, as increased muscle soreness was only evident 2 days after exercise (Fig. 1), and SICI had returned to baseline levels at this time.
In contrast to fatigue or DOMS, it is well known that SICI can be reduced by afferent input (47), and there is likely to be a change in the activity of several muscle afferents after eccentric exercise. For example, groups III and IV muscle afferents are sensitive to several parameters of muscle injury, such as the release of biochemical substrates (bradykinin, protaglandin) and factors associated with inflammation (neuropeptides, histamine), which may increase the spontaneous activity of these small-diameter muscle afferents (37). In particular, previous studies of the inflammatory response after eccentric exercise have generally shown significant increases in neutrophil infiltration that occur between 1 and 12 h after exercise (20, 43) but not at 24 h or 48 h after exercise (32), which matches the time course of the change in SICI observed in the current study. Increased activation of these small-diameter afferents may then promote a reflexively induced increase in gamma motor neuron activity (27) that can influence muscle spindle afferent activity during long-lasting contractions (31). We therefore suggest that one possible cause of reduced SICI after eccentric muscle damage is a short-term change (<24 h) in afferent feedback in the muscle due to muscle damage. An alternative explanation is that the effect of muscle damage on SICI may be longer lasting but masked by other physiological changes that occur 2 days after exercise. For example, it is known that experimental muscle pain induced by injection of hypertonic saline results in an increase in SICI (53); so, it is possible that the decreased SICI observed after muscle damage is offset by the increased SICI due to muscle soreness 2 days after exercise. However, this latter possibility is less likely, because SICI had recovered 2 days after exercise in both the relaxed and active muscle, and DOMS is only typically experienced when the muscle is active (45).
In conclusion, intracortical inhibition is considered to be crucial in modulating the output of the motor cortex and is altered with different patterns of muscle use in health and disease. We have used TMS to quantify the change in intracortical inhibition after eccentric exercise that induced muscle damage in the elbow flexor muscles of healthy, young adults. We found that eccentric exercise resulted in reduced intracortical inhibition when measured 2 h after the exercise, providing the first evidence of altered motor cortical control after eccentric muscle damage. Intracortical inhibition recovered 2 days after exercise in both resting and active muscle when muscle pain and soreness were present, suggesting that DOMS from eccentric exercise is unlikely to influence intracortical inhibition. The change in intracortical inhibition observed 2 h after exercise suggests that eccentric muscle damage has widespread effects throughout the motor system, including the motor cortex, and opens the door to test novel therapeutic interventions that act to modulate cortical excitability (e.g., training, immobilization, muscle vibration) in an effort to improve motor performance with muscle damage or injury.
No conflicts of interest, financial or otherwise, are declared by the authors.
Author contributions: B.M.P. and J.G.S. conception and design of research; B.M.P. and J.G.S. performed experiments; B.M.P. and J.G.S. analyzed data; B.M.P. and J.G.S. interpreted results of experiments; B.M.P. and J.G.S. prepared figures; B.M.P. and J.G.S. drafted manuscript; B.M.P. and J.G.S. edited and revised manuscript; B.M.P. and J.G.S. approved final version of manuscript.
- Copyright © 2012 the American Physiological Society