Pharmacological attenuation of group III/IV muscle afferents improves endurance performance when oxygen delivery to locomotor muscles is preserved

We sought to investigate the role of group III/IV muscle afferents in limiting endurance exercise performance, independently of their role in optimizing locomotor muscle O delivery. While breathing 100% O to ensure a similar arterial O content ([Formula: see text]) in both trials, eight male cyclists performed 5-km time trials under control conditions (H ) and with lumbar intrathecal fentanyl (H ) impairing neural feedback from the lower limbs. After each time trial, common femoral artery blood flow (FBF) was quantified (Doppler ultrasound) during constant-load cycling performed at the average power of the preceding time trial. The assessment of end-tidal gases, hemoglobin content and saturation, and FBF facilitated the calculation of leg O delivery. Locomotor muscle activation during cycling was estimated from vastus lateralis EMG. With electrical femoral nerve stimulation, peripheral and central fatigue were quantified by pre- to postexercise decreases in quadriceps twitch torque (ΔQ ) and voluntary activation (ΔVA), respectively. FBF (~16 mL·min ·W ; = 0.6), [Formula: see text] (~24 mL O /dL; = 0.9), and leg O delivery (~0.38 mL O ·min ·W ; = 0.9) were not different during H and H . Mean power output and time to completion were significantly improved by 9% (~310 W vs. ~288 W) and 3% (~479 s vs. ~463 s), respectively, during H compared with H . Quadriceps muscle activation was 9 ± 7% higher during H compared with H ( < 0.05). ΔQ was significantly greater in H compared with H (54 ± 8% vs. 39 ± 9%), whereas ΔVA was not different (~5%; = 0.3) in both trials. These findings reveal that group III/IV muscle afferent feedback limits whole body endurance exercise performance and peripheral fatigue by restricting neural activation of locomotor muscle. Group III/IV muscle afferent feedback facilitates endurance performance by optimizing locomotor muscle O delivery but also limits performance by restricting neural drive to locomotor muscle. To isolate the performance-limiting effect of these sensory neurons, we pharmacologically attenuated their central projection during a cycling time trial while controlling for locomotor muscle O delivery. With no difference in leg O delivery, afferent blockade attenuated the centrally mediated restriction in motoneuronal output and improved cycling performance.