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Somatosensory feedback from the limbs exerts inhibitory influences on central neural drive during whole body endurance exercise.

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  • 1. John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin-Madison Medical School, Madison, Wisconsin, USA.
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    • Amann M 1
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Journal of Applied Physiology (Bethesda, Md. : 1985), 11 Sep 2008, 105(6):1714-1724
https://doi.org/10.1152/japplphysiol.90456.2008 PMID: 18787091 PMCID: PMC2612475

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Abstract 

We investigated whether somatosensory feedback from contracting limb muscles exerts an inhibitory influence on the determination of central command during closed-loop cycling exercise in which the subject voluntarily determines his second-by-second central motor drive. Eight trained cyclists performed two 5-km time trials either without (5K(Ctrl)) or with lumbar epidural anesthesia (5K(Epi); 24 ml of 0.5% lidocaine, vertebral interspace L(3)-L(4)). Percent voluntary quadriceps muscle activation was determined at rest using a superimposed twitch technique. Epidural lidocaine reduced pretime trial maximal voluntary quadriceps strength (553 +/- 45 N) by 22 +/- 3%. Percent voluntary quadriceps activation was also reduced from 97 +/- 1% to 81 +/- 3% via epidural lidocaine, and this was unchanged following the 5K(Epi), indicating the presence of a sustained level of neural impairment throughout the trial. Power output was reduced by 9 +/- 2% throughout the race (P < 0.05). We found three types of significant effects of epidural lidocaine that supported a substantial role for somatosensory feedback from the exercising limbs as a determinant of central command throughout high-intensity closed-loop cycling exercise: 1) significantly increased relative integrated EMG of the vastus lateralis; 2) similar pedal forces despite the reduced number of fast-twitch muscle fibers available for activation; 3) and increased ventilation out of proportion to a reduced carbon dioxide production and heart rate and increased blood pressure out of proportion to power output and oxygen consumption. These findings demonstrate the inhibitory influence of somatosensory feedback from contracting locomotor muscles on the conscious and/or subconscious determination of the magnitude of central motor drive during high intensity closed-loop endurance exercise.

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J Appl Physiol (1985). 2008 Dec; 105(6): 1714–1724.
PMCID: PMC2612475
PMID: 18787091

Somatosensory feedback from the limbs exerts inhibitory influences on central neural drive during whole body endurance exercise

Markus Amann,1,2 Lester T. Proctor,3 Joshua J. Sebranek,3 Marlowe W. Eldridge,1 David F. Pegelow,1 and Jerome A. Dempsey1
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Abstract

We investigated whether somatosensory feedback from contracting limb muscles exerts an inhibitory influence on the determination of central command during closed-loop cycling exercise in which the subject voluntarily determines his second-by-second central motor drive. Eight trained cyclists performed two 5-km time trials either without (5KCtrl) or with lumbar epidural anesthesia (5KEpi; 24 ml of 0.5% lidocaine, vertebral interspace L3–L4). Percent voluntary quadriceps muscle activation was determined at rest using a superimposed twitch technique. Epidural lidocaine reduced pretime trial maximal voluntary quadriceps strength (553 ± 45 N) by 22 ± 3%. Percent voluntary quadriceps activation was also reduced from 97 ± 1% to 81 ± 3% via epidural lidocaine, and this was unchanged following the 5KEpi, indicating the presence of a sustained level of neural impairment throughout the trial. Power output was reduced by 9 ± 2% throughout the race (P < 0.05). We found three types of significant effects of epidural lidocaine that supported a substantial role for somatosensory feedback from the exercising limbs as a determinant of central command throughout high-intensity closed-loop cycling exercise: 1) significantly increased relative integrated EMG of the vastus lateralis; 2) similar pedal forces despite the reduced number of fast-twitch muscle fibers available for activation; 3) and increased ventilation out of proportion to a reduced carbon dioxide production and heart rate and increased blood pressure out of proportion to power output and oxygen consumption. These findings demonstrate the inhibitory influence of somatosensory feedback from contracting locomotor muscles on the conscious and/or subconscious determination of the magnitude of central motor drive during high intensity closed-loop endurance exercise.

Keywords: nociception, control of breathing, exercise hyperpnea, cardiorespiratory response, muscle metaboreflex, ascending sensory pathway

a major determinant of exercise performance is the level of central motor drive to the working limbs “chosen” by the subject. Significant roles for both feedforward and feedback mechanisms have been suggested to influence the magnitude of central motor drive (36, 37, 48, 54, 63, 75). Our previous data (3, 4, 9, 45, 67) obtained during high-intensity whole body endurance exercise under varying conditions of oxygenation or prefatigue showed that the magnitude of central motor output, as indicated by changes in power output and muscle EMG, related inversely to the rate of development of peripheral muscle fatigue and associated intramuscular bioenergetic changes. Although the interpretations of these findings were challenged (7, 61), others have also shown a negative correlation between intramuscular metabolites known to cause peripheral fatigue (i.e., H+, phosphates) and time to exhaustion and found a nearly identical intramuscular metabolic milieu at end exercise despite different performances resulting from varying levels of arterial oxygenation or prefatigue (22, 42, 43, 69). Based on these previous findings, we proposed that somatosensory feedback from the fatiguing locomotor muscles exerts inhibitory influence on central motor drive to modulate and/or limit the development of peripheral muscle fatigue during high-intensity whole body endurance exercise, presumably to avoid a severe disturbance of locomotor muscle homeostasis (3, 4). A similar feedback loop is thought to exist during maximal isometric contractions of a single muscle (13, 35, 36, 54, 83). The key component of our proposed regulatory mechanism during high-intensity whole body exercise is the afferent arm consisting of both myelinated (group III) and unmyelinated (group IV) nerve fibers, which increase their spontaneous discharge (and therefore their cortical projection) in the presence of metabolic byproducts of fatigue (1, 46, 52, 55, 68).

Previous studies have already blocked peripheral feedback during moderate-intensity constant workload cycling exercise and observed increases in cardiorespiratory response (20, 29, 33, 44, 70, 71). However, the augmented central command with epidural blockade in these studies was not “voluntary” but rather due to the effects of the local anesthetic on locomotor muscle strength, an impact that made increases in central motor drive inevitable to maintain the required fixed workload. In the present study, we determined the effects of pharmacologic blockade of ascending sensory pathways during closed loop time trial exercise on the level of central neural drive voluntarily selected by the subject. Based on our correlative data, as summarized above, we hypothesized that feedback from working limbs inhibits central neural drive.

METHODS

Subjects

Eight competitive male cyclists volunteered to participate in the study [age = 23.2 ± 2.1 years, body mass = 71.6 ± 2.0 kg, stature = 1.78 ± 0.1 m, maximal O2 consumption = 64.4 ± 3.0 ml·kg−1·min−1, resting single leg quadriceps maximal voluntary contraction (MVC) = 553 ± 45 N]. Written, informed consent was obtained from each participant. The protocol was approved by the University of Wisconsin's Health Sciences Institutional Review Board.

Protocol

At preliminary visits to the laboratory, subjects were thoroughly familiarized with the procedures used to assess neuromuscular functions. All participants performed a practice 5-km cycling time trial and a maximal incremental exercise test [20 W + 25 W/min (10)] on a computer-controlled electromagnetically braked cycle ergometer (Velotron, Elite model, Racer Mate, Seattle, WA) for the determination of peak power output and maximal O2 consumption. On separate days and in random order, all participants performed two time trials (5), with (5KEpi) and without (5KCtrl) epidural anesthesia.

All time trials were preceded by a 10-min warm-up at 1.5 W/kg body mass, and the subjects remained seated throughout exercise. Before the start of the time trials, an antecubital intravenous catheter was inserted, and a bolus injection of ~500 ml of normal saline was administered. The catheter was removed after completion of the experiment. To avoid initial peak power outputs, subjects were instructed to slowly pick up their pace; the recording period started after mean power output and pedal frequency, adopted from the practice time trial, were reached (within 10–15 s). Quadriceps strength and percent voluntary quadriceps muscle activation were assessed before exercise. The subjects were naive to the purpose of the study, the expected outcomes, and the variables of interest. Each exercise session was separated by at least 48 h and was completed at the same time of day. Subjects were instructed to refrain from caffeine for 12 h and stressful exercise for 48 h before each exercise trial. Ambient temperature and relative humidity were not different between conditions.

Exercise Responses

Ventilation and pulmonary gas exchange were measured breath-by-breath at rest and throughout exercise using an open-circuit system including two pneumotachographs (Hans Rudolph, model 3800) (inspiration, expiration) and two Perkin-Elmer mass spectrometer (model 1100) for the analysis of mixed expired and end-tidal gases (40). Arterial O2 saturation was estimated using a pulse oximeter (Nellcor N-595, Pleasanton, CA) with adhesive forehead sensors. Heart rate was measured from the R-R interval of an electrocardiogram using a three-lead arrangement. Ratings of perceived exertion for dyspnea and limb discomfort were obtained at rest and after completion of each trial using Borg's modified CR10 scale (14). Arterialized (Finalgon, Boehringer Ingelheim, Ingelheim, Germany) capillary blood samples were collected from an earlobe at rest and every kilometer during the time trials for determination of total whole blood lactate concentration using an electrochemical analyzer (YSI 1500 Sport, Yellow Springs, OH). Mean arterial blood pressure (MAP) was measured on the left arm at rest, 5 min into the warm-up, and during the time trials (kilometer 1) using an automated blood pressure recorder (Dinamap 1846 SX). Power output and pedal frequency were measured continuously throughout the time trials. To estimate alterations in pedal forces, we calculated, for each pedal revolution, the mean force component perpendicular to the pedal (power output = pedal force × angular velocity).

Neuromuscular Function

Electromyography.

Quadriceps EMGs were recorded from the right vastus lateralis, vastus medialis, and rectus femoris using monitoring electrodes with full-surface solid adhesive hydrogel (Kendall H59P, Mansfield, MA), with on-site amplification. Electrodes were placed in a bipolar electrode configuration over the middle of the respective muscle belly. The active electrode was placed over the motor point of the muscle. The recording electrode was moved along the muscle until an acceptable configuration (confirmed by a “maximal” M-wave shape) was achieved. The reference electrode was placed over an electrically neutral site (anterior border of the tibia, neck of fibula). The position of the EMG electrodes was marked with indelible ink to ensure that they were placed in the same location at subsequent visits. Correct electrode configuration was checked before the beginning of every experiment. To minimize movement artifacts, electrode cables were fastened to the subject's quadriceps using medical adhesive tape and wrapped in elastic bandage. The vastus lateralis, vastus medialis, and rectus femoris electrodes were used to record 1) magnetically evoked compound muscle action potentials (M waves) to evaluate changes in membrane excitability and 2) EMG for the vastus lateralis throughout exercise to estimate fatigue and central neural command. The M-wave properties included conduction time, peak amplitude, and area (18, 45, 69). Membrane excitability was maintained from pre- to postexercise in all trials as indicated by unchanged M-wave characteristics.

Raw EMG signals from the vastus lateralis corresponding to each muscle contraction during the exercise trials and the pre- and postexercise MVC maneuvers were recorded for later analyses. The EMG signals were amplified and filtered by a Butterworth band pass filter (BMA 830, CWE, Ardmore, PA) with a low-pass cutoff frequency of 10 Hz and a high-pass cut-off frequency of 1 kHz. The slope of the filters was −6 dB/octave. The filtered EMG signals were sampled at 2 kHz by a 16-bit analog-to-digital converter (PCI-MIO-16XE-50, National Instruments, Austin, TX) with custom software (Labview 6.0, National Instruments). A computer algorithm identified the onset of activity where the rectified EMG signals deviated by more than 2 standard deviations above the baselines for at least 100 ms. Each EMG burst was visually inspected to verify the timing identified by the computer. For data analysis, the integral of each burst [integrated EMG (iEMG)] was calculated using the formula

equation M1

where m is the raw EMG signal. As an estimate of central neural drive, mean iEMG over each 500-m segment of the time trial was normalized to the iEMG obtained from preexercise MVCs performed either without (control trial) or with (lumbar epidural anesthesia trial) blockade of locomotor muscle somatosensory afferent nerve fibers.

Magnetic stimulation and quadriceps strength assessment.

For a detailed description, we refer the reader to previous studies from our laboratory (8, 9). Briefly, subjects lay semi-recumbent on a table with the right thigh resting in a preformed holder, the knee joint angle set at 1.57 rad (90°) of flexion, and the arms folded across the chest. A magnetic stimulator (Magstim 200, The Magstim Company, Wales, UK) connected to a double 70-mm coil was used to stimulate the femoral nerve. The evoked quadriceps twitch force (Qtw) was obtained from a calibrated load cell (Interface, model SM 1000, Scottsdale, AZ) connected to a noncompliant strap, which was placed around the subject's right leg just superior to the ankle malleoli. To determine whether nerve stimulation was supramaximal, unpotentiated Qtw were obtained every 30 s at 50, 60, 70, 80, 85, 90, 95, and 100% of maximal stimulator power output. Similar to our previous studies (4, 6, 8, 45), a near plateau in baseline Qtw and M-wave amplitudes with increasing stimulus intensities was observed in every subject, indicating maximal depolarization of the femoral nerve. For the evaluation of locomotor muscle strength, we used six 5-s MVC of the right quadriceps separated by 30 s. For the evaluation of percent voluntary muscle activation during each MVC, we used a superimposed twitch technique (56, 72). Briefly, the force produced during a superimposed single twitch on the MVC was compared with the force produced by the potentiated single twitch delivered 5 s afterward.

Epidural Anesthesia

A 20-gauge peripheral intravenous catheter was inserted, and a bolus of ~500 ml of normal saline was infused to prevent a potential drop in blood pressure. The subjects were placed in the lateral decubitus position, and the skin and subcutaneous tissue were anesthetized at the L3–L4 vertebral interspace using 2–4 ml of 1% (10 mg/ml) lidocaine. An 18-gauge, 3.5-inch Tuohy needle was advanced to the epidural space using a saline loss of resistance technique. After the dose entered the epidural space, a 4-ml test dose of 0.75% lidocaine with 1:400,000 epinephrine was administered, and the subject was observed for signs of inadvertent intravascular and/or subarachnoid administration. After the test dose, 20 ml of 0.5% lidocaine was administered in 5-ml divided doses. The level of sensory dysesthesia was determined by using changes in the sensation of skin temperature, pin prick, and light touch on both sides of the body before and after exercise. Blood pressure, ECG, and pulse oximetry were measured before, during, and for 10-min postinjection. To evaluate the effects of 0.5% lidocaine on locomotor muscle functions, percent voluntary muscle activation and MVC force were assessed before and after the epidural injection of lidocaine. To test whether the effect of epidural anesthesia on neural impairment was maintained throughout exercise, percent voluntary muscle activation before vs. 3 min after exercise was compared. The time between the application of lidocaine and the start of the time trial was between 30 and 35 min.

Reliability, reproducibility, and technical considerations.

Quadriceps functions. For between-day reliability, the subjects repeated the assessment protocol at rest on separate visits to the laboratory. There was no systematic bias in the baseline measurements between days. Mean between-day, within-subject coefficients of variation for potentiated Qtw were 4.9% (range 1.3–7.4), 2.5% (range 0.8–6.3) for MVC, and 1.4% (range 0.0–4.1) for voluntary muscle activation. Additional reliability measures regarding magnetic nerve stimulation and technical considerations addressing the limitations of surface EMG and magnetic femoral nerve stimulation can be found in published reports (4, 6, 8, 26, 47).

Exercise trials.

After the practice trials, all eight subjects repeated 5KCtrl twice on different days for reproducibility measures. No systemic changes occurred in group mean values for performance time and mean power output. Between-day coefficients of variation for performance time were 0.8 ± 0.3% (range 0.1–1.8) and 1.6 ± 0.5% (range 0.2–3.4) for mean power output.

Statistical Analyses

Paired-sample t-tests were conducted to compare the effect of sensory feedback blockade on various physiological parameters. Pearson product-moment correlations were computed to evaluate the relationship between time trial power output and quadriceps MVC, pedal frequency, and pedal force. Results are expressed as means ± SE. Statistical significance was set at P < 0.05.

RESULTS

Effects of 0.5% Lidocaine on Resting Quadriceps Functions

Epidural lidocaine (24 ml) applied through vertebral interspace L3–L4 resulted in cutaneous hyposthesia below T6–T8. Figure 1 illustrates individual effects of the epidural anesthetic on quadriceps functions at rest. After the lidocaine injection, percent voluntary muscle activation and MVC force were significantly reduced from baseline by 17 ± 2% (97 ± 1 vs. 81 ± 3%) and 22 ± 3% (553 ± 45 vs. 435 ± 46 N), respectively (P < 0.001). Unpotentiated Qtw was not affected by lumbar anesthesia (113 ± 9 vs. 113 ± 9 N; P = 0.90), confirming that the peripheral femoral motor nerve and quadriceps motor units remained intact and unaffected during the partial spinal block.

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Individual (•) and group mean (○) effects of lumbar epidural anesthesia on resting quadriceps functions. Measures were taken before (preinjection) and ~25 min after (postinjection) the epidural administration of 24 ml of 0.5% lidocaine through the vertebral interspace L3–L4. A: lidocaine-induced reduction in voluntary muscle activation. B: maximal voluntary contraction force (MVC). P < 0.001.

Was the Level of Blockade of Sensory Feedback Maintained Throughout 5KEpi?

After exercise, the level of sensory dysesthesia (as determined by changes in the sensation of skin temperature, pin prick, and light touch) was reduced from T6–T8 before to T8–T10 after exercise. To further estimate whether the neural blockade was sustained throughout the time trial, we used the change in voluntary muscle activation from immediately before (after lidocaine injection) to 3 min after the time trial. Percent voluntary muscle activation is known to recover quickly after exercise, and it has been shown to be identical before vs. more than 2 min after high-intensity exercise (4, 8, 9, 13). Lidocaine injection reduced resting voluntary muscle activation from 97% to 81% (see above). Percent voluntary muscle activation was unchanged from before to after the time trial (81 ± 3% and 83 ± 2%, respectively; P = 0.09), indicating a sustained neural blockade.

Effects of Epidural Lidocaine on Time Trial Performance, Pedal Force and Frequency, iEMG, and Cardiorespiratory Variables

Performance variables.

Exercise performance was highly sensitive to the effects of epidural lidocaine on neuromuscular functions. Performance time was prolonged in all subjects by an average of 4.2 ± 1.2% (range 1 to 10%) and mean power output decreased by 8.9 ± 2.3% (range 2 to 19%) from 5KCtrl to 5KEpi (P < 0.05) (Table 1 and Fig. 2). The profiles for power output of an initial fall, plateau, and a terminal rise were similar for 5KCtrl and 5KEpi. There was no significant correlation between the lidocaine-induced reduction in quadriceps MVC and the reduction in mean time trial power output (r = 0.53, P = 0.17). The Pearson product-moment correlations between time trial power output and pedal frequency (r = 0.73, P < 0.001) and pedal force (r = 0.91, P < 0.001) indicate a high degree of relationship between the variables.

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Effect of partial blockade of locomotor muscle somatosensory afferents on integrated EMG (iEMG) and power output during a 5-km cycling time trial. The local anesthetic (epidural lidocaine) significantly affected resting neuromuscular functions, as indicated by a reduction in maximal voluntary muscle activation and MVC force by 17 and 22%, respectively. Furthermore, mean iEMG during the preexercise MVCs was significantly reduced from pre- to postinjection (0.24 ± 0.03 vs. 0.21 ± 0.03 V/s, respectively; P < 0.5). Hence, the epidural anesthesia trial ([open triangle]) was performed with a reduced capacity of the locomotor muscles to generate force. A: effects of lumbar epidural anesthesia on group mean iEMG of vastus lateralis normalized to the iEMG obtained during preexercise (after injection of lidocaine) MVC of the quadriceps. Each point represents the mean iEMG of the preceding 0.5-km section. Mean iEMG during the time trial was significantly increased from the control trial (5KCtrl; [filled triangle]) to the epidural anesthesia trial (5KEpi) (P = 0.04). B: group mean power output during the 5-km time trial with and without impaired afferent feedback. Subjects (n = 8) were required to reach an individual target power output before the race was launched (362 ± 14 W). Group mean power output/time to completion results were 347 ± 14 W/7.35 ± 0.10 min and 317 ± 14 W/7.66 ± 0.17 min (P < 0.05) for 5KCtrl and 5KEpi, respectively.

Table 1.

Physiological response to 2.5 km, 5 km, and mean values over 5 km of cycling at maximal self-selected effort

Control
Epidural Anesthesia
2.5 km5 kmMean over 5 km2.5 km5 kmMean over 5 km
Power output, W338±13390±23347±14303±18*350±13*317±16*
Pedal frequency, revolutions/min108±2110±2108±2101±2*102±2*102±2*
Mean force perpendicular to pedals (per revolution), N86±398±688±482±492±485±4
Exercise time, min3.67±0.057.35±0.103.83±0.08*7.66±0.17*
Heart rate, beats/min184±3196±3184±2185±2193±3183±2
Ve, l/min142±8174±8141±7157±6*174±5152±6*
Expected Ve, l/min132±6154±7132±5
f, breaths/min51±362±351±356±3*70±657±3*
Vt, liters2.85±0.182.84±0.182.85±0.182.79±0.192.56±0.18*2.69±0.18
Vo2, l/min4.01±0.174.43±0.193.95±0.193.83±0.18*4.19±0.19*3.76±0.18*
Vo2, % of Vo2max90±3100±188±285±2*94±2*82±2*
Vco2, l/min4.30±0.294.59±0.274.23±0.264.00±0.24*4.04±0.21*3.96±0.22*
Ve/Vo236.1±2.540.0±2.236.1±2.140.6±1.8*42.0±2.140.4±1.5*
Ve/Vco233.1±0.838.2±1.033.3±0.739.0±1.9*43.6±2.5*38.1±1.7*
PetO2, Torr106.9±1.2109.6±1.6106.2±1.2112.0±0.7*114.0±1.2*111.7±0.9*
SaO2, %95.5±0.592.3±0.495.4±0.596.5±0.593.7±0.996.2±0.6
RPE (dyspnea)7.6±0.47.5±0.4
RPE (limb discomfort)8.4±0.26.8±0.4*
Capillary lactate concentration, mmol/l7.1±0.410.0±0.27.1±0.37.7±0.69.8±0.57.5±0.5

Values are means ± SE; n = 8 subjects. f, respiratory frequency; PetO2, end-tidal Po2; RPE, rate of perceived exertion; SaO2, arterial blood saturation; Ve, minute ventilation; Vco2, CO2 production; Vo2, oxygen consumption; Vo2max, maximal Vo2; Vt, tidal volume. Note that all 2.5- and 5-km values (with the exemption of power output and lactate concentration) are given as mean over the preceding 250 m ( approximately 21 s). Expected Ve, Ve as expected based on calculations using the Ve/Vco2 ratio obtained from 5-km time trial without lumbar epidural anesthesia (5KCtrl) and the Vco2 values as measured during 5-km time trial with lumbar epidural anesthesia (5KEpi).

*P < 0.05 vs. 5KCtrl.

Pedal force and frequency.

Figure 3 depicts alterations in pedal force and pedal frequency during the two time trials. Group mean absolute pedal forces throughout the time trials were similar for 5KCtrl and 5KEpi (87.6 ± 3.6 and 84.8 ± 3.9 N, respectively; P = 0.19); compared with 5KCtrl, pedal forces during 5KEpi were increased out of proportion to power output (P < 0.01). Group mean pedal frequency was reduced by 5.1 ± 1.4% (range 1–13%) from 5KCtrl to 5KEpi (108 ± 2 and 102 ± 2 revolutions/min, respectively; P < 0.01).

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Relationship between voluntary power output and pedal frequency and pedal force during the 5-km time trials in 8 subjects. Both pedal frequency and pedal force are highly correlated with power output (r = 0.73 and r = 0.91, respectively). Because pedal forces were similar in both trials (P = 0.19), the substantial reduction in power output from 5KCtrl to 5KEpi was predominantly the result of the significant reduction in pedal frequency, which was presumably caused by the lidocaine-induced reduction in available fast-twitch muscle fibers. rev, Revolutions. *P < 0.05.

iEMG.

Figure 2 illustrates changes in iEMG during the time trials; each point represents the preceding 500-m segment of the time trial. Mean iEMG of the vastus lateralis was normalized to the iEMG obtained from preexercise MVC maneuvers performed either without (5KCtrl) or with (5KEpi) epidural anesthesia. On the lidocaine day, mean iEMG during the preexercise MVCs was significantly reduced from before to after injection (0.24 ± 0.03 vs. 0.21 ± 0.03 V/s, respectively; P < 0.5). Group mean average iEMG over the entire time trial was 8.9 ± 3.5% higher in 5KEpi vs. 5KCtrl (P = 0.045). This increase in average iEMG from 5KCtrl to 5KEpi occurred in seven of eight subjects (1–24%). iEMG fell progressively and similarly from kilometer 0.5 to kilometer 1.5 in 5KCtrl (11 ± 4%; P < 0.05) and 5KEpi (10 ± 1%; P < 0.01) in all eight subjects and rose again toward the end of the time trial by 18 ± 4% in all subjects in 5KCtrl (P < 0.01). However, in 5KEpi, the group mean increase in iEMG from 1.5 to 5 km was only 6 ± 6% (P = 0.31) and highly variable. Only four of eight subjects increased iEMG from kilometer 1.5 to kilometer 5 (6–36%), whereas iEMG for the remaining subjects remained either unchanged (n = 1) or further decreased between 2 and 17% (n = 3).

Cardiorespiratory responses.

Various physiological responses to 5-km time trial exercise with and without epidural anesthesia are shown in Table 1 and Fig. 4. Resting metabolic rate and various cardiorespiratory variables were not affected by the local anesthetic (P > 0.3). Furthermore, a lidocaine-induced reduction in sympathetic tone at rest can be excluded given identical MAP (98 ± 3 and 95 ± 2 mmHg; P = 0.06) and heart rate (63 ± 4 and 62 ± 3 beats/min; P = 0.62) in 5KEpi and 5KCtrl, respectively. The reduced power output throughout the lidocaine trial is reflected in a lower metabolic rate since oxygen consumption (Vo2) and carbon dioxide production (Vco2) were on average 7 ± 2% and 6 ± 2%, respectively, lower in 5KEpi vs. 5KCtrl (P < 0.05). The group mean average minute ventilation (Ve) over the time trial was 9 ± 4% higher during 5KEpi vs. 5KCtrl (P < 0.05) despite the significantly lower mean power output. The increase in Ve was achieved by a 15 ± 6% increase in breathing frequency. The ventilatory response to 5KEpi was out of proportion to the metabolic rate, as indicated by the group mean average ventilatory equivalents for O2 and CO2, which were increased from 5KCtrl to 5KEpi by 13 ± 6% and 14 ± 4%, respectively (both P < 0.05). The increases in breathing frequency and Ve/Vco2 in 5KEpi vs. 5KCtrl were present throughout the time trial. Furthermore, despite the 8.8 ± 2.3% lower mean muscle power output in 5KEpi vs. 5KCtrl, no significant differences were found in heart rate and MAP between the two trials (Table 1 and Fig. 4). MAP at the end of the warm-up (same workload in both conditions) was 99 ± 4 vs. 97 ± 5 mmHg (P = 0.87) in 5KCtrl vs. 5KEpi, respectively. MAP was substantially increased at kilometer 1; however, the difference between 5KCtrl vs. 5KEpi remained unchanged (141 ± 6 vs. 139 ± 4 mmHg, P = 0.37) in 5KCtrl vs. 5KEpi, respectively.

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Physiological responses to a 5-km cycling time trial without (5KCtrl; [filled triangle]) and with (5KEpi; [open triangle]) partially blocked somatosensory neural feedback from the fatiguing locomotor muscles. Group mean performance (average power output/time to completion) was significantly reduced from 5KCtrl (347 ± 14 W/7.35 ± 0.10 min) to 5KEpi (317 ± 14 W/7.66 ± 0.17 min). Ve, minute ventilation; Vo2, oxygen consumption; Vco2, carbon dioxide production; SpO2, arterial oxygen saturation; n = 8 subjects.

DISCUSSION

We tested the hypothesis that somatosensory afferent feedback from working and fatiguing limbs exerts inhibitory influences on central motor drive during high-intensity, closed-loop endurance exercise. Earlier studies used local anesthetics to block neural feedback during constant workload whole body exercise (see Introduction). However, the associated drug-induced reduction in locomotor muscle strength in these investigations resulted in an inevitable increase in central motor drive necessary to maintain the given absolute required fixed workload (64). In the present study, we used a unique design to test this hypothesis. Workload was not fixed, and the subjects were able to voluntarily “choose” their level of central motor drive during cycling exercise with blocked sensory feedback from the working limbs. The lumbar epidural application of a local anesthetic also affected efferent motor nerves (including fusimotor axons), leading to a significant loss in locomotor muscle strength. Accordingly, because of these confounding effects of epidural lidocaine, we did not expect to observe an increase in power output or improvement in time trial performance. However, we did observe several lines of evidence that supported a higher central neural drive with epidural anesthesia. Our study is the first to directly confirm the postulate that sensory feedback from the working limb exerts inhibitory influences on central motor drive.

Sensory and Motor Effects of Epidural Anesthesia During Exercise

The somatosensory system may be functionally divided into nonnociceptive and nociceptive ascending pathways projecting to the cerebral cortex or to the cerebellum. Local anesthetics, such as lidocaine, affect conduction of ascending and descending nerves by binding to the Na+-channel complex at the internal side of the cell membrane, which leads to the inhibition of the ion flux (17). The magnitude with which nerve conduction is affected via a given concentration of a local anesthetic has initially been suggested to differ with the type of nerve fiber; that is, conduction is inhibited more in thin myelinated and unmyelinated fibers than in thick myelinated fibers (15, 16), whereas thick myelinated fibers are only little affected by epidural anesthesia (51). However, the phenomenon of such differential blockade is now thought to be more complex. The “length of exposure” theory claims that impulse propagation can either be impeded by a full block of three consecutive nodes of Ranvier or (in case of a lower concentration of local anesthetic) by a partial block of more nodes of Ranvier over a longer nerve segment (31). Lidocaine is spatially not confined to the epidural space, and its passive diffusion to other tissue spaces, including the cerebrospinal fluid, depends not only on the volume and concentration of the injected solution but also on individual anatomic characteristics, which can explain interindividual differences of the effects of local anesthetics (Fig. 1) (76, 85). Because the dural sleeve surrounding the roots is thinner than elsewhere, epidural lidocaine is thought to first reach a blocking concentration in the roots within the sleeve (30). Nonetheless, diffusion from one tissue space to another leads to a concentration loss of the injected solution (76). The concentration of the local anesthetic outside the epidural space is presumably still sufficient to block three consecutive nodes of Ranvier in short-internode Aδ and unmyelinated C-fibers impeding nerve conduction in these muscle afferent. On the other hand, motor nerves are characterized by long-internodal distances (further diffusion necessary to achieve a conduction block), and the concentration of the diffused local anesthetic might be too low to reach a similar magnitude of blockage in these fibers (30, 31, 38). As a result of this differential conduction block, impulse propagation of sensory ascending pathways was effectively inhibited in our study. However, to a much lesser degree, conduction along the descending efferent pathway was also impaired.

With the intent to minimize the drug-induced effect on neuromuscular functions, we chose a relatively low concentration of a short-acting local anesthetic (24 ml 0.5% lidocaine) and thereby avoided the up to 40% reductions in resting muscle strength observed in previous investigations (29, 33, 49, 50, 58). Nonetheless, neuromuscular blockade was indicated by the ~17% reduction in voluntary quadriceps activation and consequently an ~22% reduction in resting MVC force output (Fig. 1). This weakness was well noted by the subjects.

To test whether the neural blockade was sustained throughout exercise, we compared the change in percent voluntary muscle activation from immediately before (following lidocaine injection) to 3 min after the time trial. This parameter has been shown to be identical before vs. more than 2 min after high-intensity exercise (4, 8, 9, 13). The observations that voluntary muscle activation was the same before vs. 3 min after exercise and sensory dysesthesia was maintained throughout exercise support the notion of a sustained degree of epidural blockade during the time trial.

It needs to be mentioned that lumbar epidural lidocaine might also have affected the blood flow distribution to the locomotor muscles. Kjaer et al. (49) found that lumbar anesthesia reduced leg vascular resistance (reduced norepinephrine spillover combined with reduced MAP) during normoxic cycling exercise, whereas cardiac output and leg blood flow were unchanged from control. In our study, MAP and heart rate during 5KEpi were increased out of proportion to the workload (revealing increased central command), perhaps indicating that a potentially reduced vascular resistance was counterbalanced and that leg blood flow was even increased vs. 5KCtrl. These presumed local increases in blood flow might have increased limb O2 delivery and therefore attenuated the oxygen sensitive rate of accumulation of metabolites known to cause fatigue (2), resulting in an overall lower stimulation of muscle metaboreceptors.

Finally, we acknowledge the possibility that the effects of the lidocaine on central motor output may have been due in part to a placebo effect of the epidural injection, per se, rather than to the drug's neural blockade properties. In subsequent ongoing studies of lumbar spinal blockade, we have used a placebo trial consisting of a sham intraspinous ligament injection of sterile normal saline at vertebral interspace L3–L4. We found that the sham injection did not provoke any of these effects (unpublished observations). In view of these recent data, we believe that the effects of epidural lidocaine that we observed were due to the neural blockade effects of the anesthesia rather than due to the injection per se.

Lidocaine-Induced Alterations in Motor Unit Recruitment and Functional Consequences for Exercise Performance

Important for the interpretation of our data is the consideration of the inevitable functional consequences of the lidocaine-induced changes in nerve fiber excitability and impulse conduction on the motor unit recruitment of the lower limbs. The predominant actions of local anesthetics on conducting nerve fibers are transient decreases in excitability and conduction velocity in combination with a reduction of intrinsic oscillatory aftereffects of impulse discharge (66). These alterations result in a reduced net excitatory current in the peripheral motor neurons, leading, according to the size principle (23), to a failure to reach the activation threshold of large motor units (i.e., fast-twitch muscle fibers) (27). Consequently, less type II fibers can be recruited and the overall number of available motor units is reduced after epidural lidocaine injection. Type II fibers are characterized by high contractile forces and high shortening velocities and have been shown to be significant determinants not only of peak leg muscle forces but also of peak power output, pedal force, and pedal frequency (27, 32, 41, 74). The lidocaine-induced reduction in the availability of predominantly type II fibers might therefore not only explain the substantial decrease in resting peak quadriceps strength but also the reduction in pedal frequency during 5KEpi (27). However, despite the reduction in available type II fibers during 5KEpi, the mean force applied perpendicular to the crank arms (surrogate for active locomotor muscle force) was similar in both time trials (Fig. 3). Therefore, to generate comparable absolute pedal forces during 5KEpi (increased out of proportion to workload), additional low threshold motor units had to be recruited or each motor unit had to perform more work. The similar lactate values despite a substantially lower power output and a lower number of available motor units during 5KEpi vs. 5KCtrl support the notion that each available motor unit performed more work. In conclusion, a compensation for the reduction of available type II fibers was possible with respect to pedal force (similar in both trials despite substantial differences in power output) by increasing type I motor unit recruitment; however, it was not possible to compensate for the decrement in shortening velocity (i.e., pedal frequency) presumably evoked by the reduction of available type II fibers, and the net result was a reduced power output during 5KEpi vs. 5KCtrl.

Increased Central Neural Drive via Feedback Blockade

The evaluation of central command during systemic exercise is presently restricted to indirect estimates (12, 20, 24, 26, 34, 44, 57, 70), and various limitations need to be considered before valid conclusions can be drawn. In this investigation, we relied on different indicators known to reflect changes in central command, and our indirect evidence for a voluntarily increase in central motor drive in the absence of somatosensory afferent feedback from the fatiguing locomotor muscles is threefold.

First, relative electromyographic activity obtained from the vastus lateralis suggests that on average and over time the “drive” to race averaged 9% stronger when neural feedback was blocked. Interestingly, the change of iEMG over the 5-km distance was similar in both time trials but upregulated throughout the 5KEpi (Fig. 2). In support of the use of iEMG as an index of central motor drive, we have previously observed vastus lateralis iEMG to increase significantly over time at a constant work rate of heavy intensity, and this time-dependent increase in EMG coincided with the rate of development of peripheral quadriceps fatigue, as determined via pre- vs. postexercise reduction in Qtw (6, 8, 9). However, potential limitations of surface EMG to reflect central motor drive need to be considered (11, 28, 47, 54, 65, 84). For example, significant filtering effects on the EMG will occur, which are related to the thickness of the subcutaneous tissues and overrepresent motor units located near the recording electrodes. Additionally, amplitude cancellation can attenuate increases in motor unit activity measured by surface EMG. This insensitivity of the surface EMG technique might underestimate increases in neural drive (47). Furthermore, the depression (65) and/or facilitation (54) of the efficacy of corticospinal synapses on motoneurons and associated effects on motoneuronal output during voluntary muscle contractions need to be considered. Based on these findings, it has been suggested that the motoneuron can no longer be viewed as a “simple way station” between the motor cortex and the peripheral muscle (39); consequently, surface EMG might underestimate or overestimate the motor cortical output, that is, central motor drive.

Second, epidural lidocaine presumably reduced the number of available type II muscle fibers that can voluntarily be activated (see above). Regardless, absolute pedal force (i.e., active locomotor muscle force) was similar in both trials (Fig. 3; pedal force during 5KEpi was even increased out of proportion to power output), indicating that the subjects were able to compensate for the reduced force contribution from type II fibers (presumably either via the additional recruitment of additional type I motor units or each available motor unit had to perform more work). In any case, the neural activation of the locomotor muscles had to be substantially increased to generate comparable absolute pedal forces in both time trials, given the negative effects of epidural lidocaine on the excitatory current in the peripheral motoneurons during 5KEpi. The reduced pedal frequency in the face of an increased central motor drive is not in contrast to these considerations. The motor units contributing to the power output during 5KEpi were physically simply not capable of achieving very high shortening velocities and thus the loss in power output attributable to a reduction in revolutions per minute could not have been compensated by the increased neural drive.

Finally, cardiorespiratory variables, namely, Ve, heart rate, and blood pressure, are well known to reliably reflect increases in central motor drive (12, 20, 21, 24, 25, 34, 44, 53, 57–59, 70, 73, 77–82). In the present study, a substantially increased central command during the time trial with impaired neural feedback (vs. 5KCtrl) was reflected by the similar or even greater cardiorespiratory response to exercise despite the significantly lower workload and metabolic rate during 5KEpi vs. 5KCtrl. In other words, heart rate and MAP were nearly identical and Ve was even significantly increased despite the lower power output, Vo2, and Vco2 during 5KEpi vs. 5KCtrl (Fig. 4). Furthermore, the greater Ve/Vco2 was sustained throughout 5KEpi (vs. 5KCtrl), suggesting a greater sensitivity of exercise hyperpnea to increases in central command compared with heart rate and MAP. We calculated Ve (from Ve/Vco2 as measured during 5KCtrl) as it would be expected during a hypothetical control time trial performed at a metabolic rate (Vco2) identical to that measured during 5KEpi (Table 1). Ve during 5KEpi was 13–19% higher, as would be expected from the metabolic rate, and these theoretical calculations further emphasize the substantial effect of increased central command on Ve. Our observations are consistent with earlier findings by Asmussen et al. (12) and Galbo et al. (34), who found exaggerated ventilatory responses to constant workload dynamic exercise with curare (partial neuromuscular blockade and intact afferent feedback), whereas heart rate and MAP responses were less affected by the increased central command. These trends were even further pronounced with lumbar epidural anesthesia during constant workload dynamic exercise characterized by higher ventilation but similar heart rate and MAP compared with control exercise (29). Lastly, although reductions in pedaling frequency have been shown to reduce Ve/Vco2 particularly for pedaling rates above 100 (19), the exercise hyperventilation in our study occurred despite a reduced pedaling frequency, which accompanied the partial neuromuscular blockade (Table 1). We note further that the exercise hyperventilation resulting from an increased central motor command occurred entirely due to an increase in breathing frequency.

What Determines Central Motor Command During Closed-Loop, High-Intensity Whole Body Endurance Exercise?

We have recently proposed that, during high-intensity whole body endurance exercise, the rate of development of peripheral muscle fatigue is one of the key determinants of central motor drive. Furthermore, we proposed that central motor drive is regulated, via feedback pathways from the locomotor muscles, to prevent the development of peripheral fatigue beyond a “critical threshold” (3, 4, 9). The purpose of such a negative influence on the determination of the magnitude of central motor output could be the protection of the muscle from damage associated with a disturbance of muscle homeostasis, but possibly at the expense of truly maximal exercise performance (36). We assumed that the ability to consciously and/or subconsciously regulate central motor drive and therefore muscle power output, with the purpose to remain below or at this critical threshold, might be due to group III/IV muscle afferents transmitting nociceptive and/or biochemical milieu-related input from the working muscles to supraspinal areas of the central nervous system involved in the regulation of the magnitude of central motor drive. The present study now provides evidence to support our previous assumption. The significantly higher central motor drive with blocked somatosensory feedback from the legs confirms the inhibitory influence of these metaboreceptors and nociceptors on central motor drive during high intensity whole body exercise.

On the basis of the myoelectrical response to transcranial magnetic stimulation, an inhibitory influence of group III/IV muscle afferents on motor cortical output cells has previously been shown during isolated muscle exercise (54). These authors increased the activity in group III/IV afferents via intramuscular injection of hypertonic saline during elbow flexion and extension and showed a progressive inhibition of the motor cortex with increasing somatosensory feedback. Consistent with these data, our present findings of significantly higher central motor drive with blocked somatosensory feedback from the legs confirm the inhibitory influence of these metaboreceptors and nociceptors on central motor drive during high-intensity whole body endurance exercise.

We observed in this and previous studies (3, 4) that power output rose along with iEMG (surrogate for central neural drive) during the final ~500 m of both time trials (Fig. 2), indicating that central motor drive was submaximal during the majority of both trials (i.e., blocked and unblocked). It bears emphasis that the elevated central motor drive during 5KEpi was still not at a maximal level since it also increased over the final ~500 m. This observation emphasizes that somatosensory feedback (substantially attenuated in our lidocaine experiments) from the working muscles is only one of several potential factors determining the magnitude of central motor drive and indicates the importance of the feed-forward component during closed-loop exercise. The moment-to-moment determination of the magnitude of central motor drive within the central nervous system is likely the result of a complex interaction between feedforward as well as various feedback mechanisms. The relative contributions of these determinants to the appropriate regulation of central command will change with exercise modality (duration, intensity, open-loop vs. closed-loop, “end-spurt” vs. middle of the time trial, and so forth) (26), environmental conditions (e.g., hypoxia, heat) (9, 60), or nutritional circumstances (62) and therefore limits our ability to generalize the interpretation of our recent data. However, our present results do provide experimental evidence for a significant role of feedback influences from the working and fatiguing locomotor muscles on the voluntary determination of central motor drive during high-intensity closed-loop endurance exercise.

GRANTS

This research was supported by National Heart, Lung, and Blood Institute Grant RO1 HL-15469. M. Amann was the recipient of a Postdoctoral Fellowship from the American Heart Association.

Acknowledgments

We thank Cynthia E. Bird and Rose E. Voelker for valuable assistance with lactate assessment and EMG data analyzes, respectively.

Notes

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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