Ensemble input of group III/IV muscle afferents to CNS: A limiting factor of central motor drive during endurance exercise from normoxia to moderate hypoxia

Abstract

We recently hypothesized that across the range of normoxia to severe hypoxia the major determinant of central motor drive (CMD) during endurance exercise switches from a predominantly peripheral origin to a hypoxic-sensitive central component of fatigue. We found that peripheral locomotor muscle fatigue (pLMF) is the prevailing factor limiting central motor drive and therefore exercise performance from normoxia to moderate hypoxia (SaO2 > 75 %). In these levels of arterial hypoxemia, the development of pLMF is confined to a certain limit which varies between humans—pLMF does not develop to this limit in more severe hypoxia (SaO2 < 70 %) and exercise is prematurely terminated presumably to protect the brain from insufficient O2 supply. Based on the observations from normoxia to moderate hypoxia, we outlined a model suggesting that group III/IV muscle afferents impose inhibitory influences on the determination of CMD of working humans during high-intensity endurance exercise with the purpose to regulate and restrict the level of exercise-induced pLMF to an “individual critical threshold.” To experimentally test this model, we pharmacologically blocked somatosensory pathways originating in the working limbs during cycling exercise in normoxia. After initial difficulties with a local anesthetic (epidural lidocaine, L3 –L4) and associated loss of locomotor muscle strength we switched to an intrathecally applied opioid analgesic (fentanyl, L3 –L4). These experiments were the first ever to selectively block locomotor muscle afferents during high-intensity cycling exercise without affecting maximal locomotor muscle strength. In the absence of opioid-mediated neural feedback from the working limbs, CMD was increased and end-exercise pLMF substantially exceeded, for the first time, the individual critical threshold of peripheral fatigue. The outcome of these studies confirm our hypothesis claiming that afferent feedback inhibits CMD and restricts the development of pLMF to an individual critical threshold as observed from normoxia up to moderate hypoxia.