Group III/IV Muscle Afferents Restrict Intramuscular Metabolic Perturbation In Exercising Humans

Abstract

Group III/IV muscle afferent feedback limits the development of peripheral fatigue during intense endurance exercise to a critical threshold, by restricting central motor drive (CMD). Pharmacological blockade of these sensory neurons inhibits this regulatory mechanism and causes this threshold to be exceeded with the consequence of excessive end-exercise fatigue. However, the intramuscular metabolic perturbation associated with this altered level of peripheral fatigue is unknown. PURPOSE: To investigate the role of group III/IV locomotor muscle afferents in limiting intramuscular metabolic perturbation during intense cycling exercise. METHODS: Eight subjects performed a 5 km cycling time trial under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing feedback from the μ-opioid receptor-sensitive lower limb muscle afferents (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Exercise-induced changes in intramuscular metabolites were determined using liquid chromatography (mass spectrometry). Quadriceps fatigue was quantified via pre- to post-exercise changes in potentiated quadriceps twitch force (ΔQtw) evoked by electrical femoral nerve stimulation. Central fatigue was measured by comparing pre- to post-exercise changes in quadriceps voluntary activation (ΔVA). RESULTS: Although power output during the first half of the time trial with FENT was 10 ± 1% higher compared to CTRL, it was 11 ± 4% lower during the second half (P < 0.01). ΔQtw was greater following FENT than CTRL (−52 ± 2 vs. −31 ± 1%, P < 0.001); ΔVA was also more pronounced in FENT than CTRL (-11 ± 3% vs. -6 ± 1%, P < 0.001). The pre- to post-exercise-induced increase in intramuscular inorganic phosphate, adenosine diphosphate, and lactate was 133%, 190% and 129% greater in FENT than CTRL (P < 0.001), respectively. Phosphocreatine depletion was 47% greater in FENT compared to CTRL (P < 0.01). CONCLUSIONS: Group III/IV muscle afferents limit peripheral fatigue and intramuscular metabolic perturbation during intense endurance exercise. Therefore, the intramuscular metabolic milieu, representing a key stimulus for group III/IV afferent feedback which is in turn associated with reductions in CMD, could be highly regulated to prevent the development of excessive peripheral fatigue during whole body endurance exercise.