Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans

Abstract

Key points: The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise-induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive locomotor muscle afferents during a 5 km cycling time trial. The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural 'drive' to working locomotor muscle and limits the exercise-induced intramuscular metabolic perturbation. Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance.

Abstract: To investigate the role of metabo- and mechanosensitive group III/IV muscle afferents in limiting the intramuscular metabolic perturbation during whole body endurance exercise, eight subjects performed 5 km cycling time trials under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing lower limb muscle afferent feedback (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Motoneuronal output was estimated through vastus lateralis surface electromyography (EMG). Exercise-induced changes in intramuscular metabolites were determined using liquid and gas chromatography-mass spectrometry. Quadriceps fatigue was quantified by pre- to post-exercise changes in potentiated quadriceps twitch torque (ΔQTsingle ) evoked by electrical femoral nerve stimulation. Although motoneuronal output was 21 ± 12% higher during FENT compared to CTRL (P < 0.05), time to complete the time trial was similar (∼8.8 min). Compared to CTRL, power output during FENT was 10 ± 4% higher in the first half of the time trial, but 11 ± 5% lower in the second half (both P < 0.01). The exercise-induced increase in intramuscular inorganic phosphate, H(+) , adenosine diphosphate, lactate and phosphocreatine depletion was 55 ± 30, 62 ± 18, 129 ± 63, 47 ± 14 (P < 0.001) and 27 ± 14% (P < 0.01) greater in FENT than CTRL. ΔQTsingle was greater following FENT than CTRL (-52 ± 2 vs -31 ± 1%, P < 0.001) and this difference was positively correlated with the difference in inorganic phosphate (r(2) = 0.79; P < 0.01) and H(+) (r(2) = 0.92; P < 0.01). In conclusion, during whole body exercise, group III/IV muscle afferents provide feedback to the CNS which, in turn, constrains motoneuronal output to the active skeletal muscle. This regulatory mechanism limits the exercise-induced intramuscular metabolic perturbation, preventing an abnormal homeostatic challenge and excessive peripheral fatigue.

Figure 1. Effect of attenuating group III/IV afferent feedback on power output and quadriceps EMG during 5 km cycling time trial

Each data point represents the average over the preceding 100 m section. Vastus lateralis (VL) and rectus femoris (RF) RMS EMGs were normalized to the RMS recorded during pre‐exercise MVC. Subjects were required to reach an individual target power output (260 ± 15 W) before the race was launched. Although the overall VL and RF EMGs were significantly higher during FENT (○) compared to CTRL (●), the average power output was similar between the two trials. W _peak: peak power output measured during the maximal incremental exercise test (296 ± 37 W). Data are presented as group mean ± SEM. ^* P < 0.05 vs control.

Figure 2. Effect of attenuating group III/IV afferent feedback on intramuscular metabolic perturbations evoked by a 5 km cycling time trial

Muscle samples were obtained from the vastus lateralis immediately after exercise. An occlusion cuff placed at the top of the thigh was inflated at the end of exercise and maintained at 250 mmHg until muscle sampling was completed (<30 s). Muscle pH and metabolite data are expressed in absolute units and per cent change from baseline, respectively. ^* P < 0.05 vs control; ^# P < 0.001 vs baseline.

Figure 3. Effect of attenuating group III/IV afferent feedback on quadriceps fatigue following a 5 km cycling time trial

Despite a similar overall exercise performance (∼8.8 min), end‐exercise quadriceps fatigue was exacerbated in FENT (○) compared to CTRL (●) (P < 0.001). Pre‐exercise values for maximal voluntary contraction (MVC), potentiated quadriceps twitch torque at 1 Hz (QT_Single), 10 Hz (QT₁₀) and 100 Hz (QT₁₀₀) were not different between conditions (274 ± 25, 87 ± 5, 133 ± 5 and 140 ± 7 N.m, respectively). ^* P < 0.05 vs control; ^† P < 0.05 vs baseline in control; ^‡ P < 0.05 vs baseline in fentanyl.

Figure 4. Relationship between quadriceps fatigue and intramuscular metabolites

Data are expressed as per cent difference between FENT and CTRL for both intramuscular metabolites and potentiated quadriceps twitch torque (QT_Single). Continuous lines represent best‐fit linear regression.