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

Abstract

Key pointsr 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.r 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.r 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.r 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 ( QT single ) 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 (ß8.8 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. QT single 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.

Bioenergetics and ATP Synthesis during Exercise

“…Interestingly, although not highlighted in our group’s previous work (7), the attenuation of group III/IV muscle afferent feedback appeared to impair muscle efficiency during cycling exercise. This was evinced by a greater PCr depletion and hydrogen ion accumulation in the vastus lateralis, despite an unchanged mean power output, following the fentanyl-induced attenuation of feedback from leg muscle afferents (7).…”

“…Mechanistically, this constraint appears to be mediated by group III/IV muscle afferents, which innervate the extracellular space of skeletal muscle and respond in a dose-dependent manner to the mechanical and metabolic stimuli associated with muscle contractions to provide feedback to the brain and spinal cord (25). Specifically, [PCr], [Pi], adenosine diphosphate ([ADP]), [lactate], and pH were perturbed to a greater extent with the fentanyl-induced attenuation of feedback from these leg muscle afferents (7). However, the influence of group III/IV muscle afferents on exercising skeletal muscle bioenergetics (i.e.…”

“…This was evinced by a greater PCr depletion and hydrogen ion accumulation in the vastus lateralis, despite an unchanged mean power output, following the fentanyl-induced attenuation of feedback from leg muscle afferents (7). However, given the large variation in power output during these cycling time trials and utilization of highly localized, periodic biopsies, such an observation needs to be investigated using an experimental design better suited to assess such a phenomenon (i.e.…”

Limitation of fatigue and performance during exercise: the brain–muscle interaction

“…Blain GM, Mangum TS, Sidhu SK, Weavil JC, Hureau TJ, Jessop JE, Bledsoe AD, Richardson RS & Amann M (2016). Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans.…”

“…In a recent collaborative study (Blain et al 2016), Amann's group and mine have joined their efforts to determine the role of group III-IV muscle afferent feedback in restraining muscle activation and limiting the exercise-induced intramuscular metabolic perturbation and peripheral fatigue. Specifically, on the basis of an experimental protocol originally developed by Dempsey in 2009 (Amann et al 2009), the central projections of muscle afferents were pharmacologically attenuated, using intrathecal fentanyl, during a 5 km cycling time trial.…”