Regular physical activity is an important treatment constituent for chronic pain. To unravel the neuronal influence of exercise on pain, we investigated the neuronal changes during exercise-induced hypoalgesia in endurance athletes and controls. Twenty-two athletes (mean age: 33.3 ± 10.8 years) and twenty non-athletes (mean age: 28.9 ± 9.0 years) underwent High-Intensity Interval Training (HIIT) and pressure pain tests, while brain oxygenation was monitored using functional near-infrared spectroscopy to cover key regions of pain processing: the prefrontal cortex (PFC), sensory motor cortices, and posterior parietal cortex (PPC). During HIIT, both groups exhibited a steady increase in PFC oxyhemoglobin, with athletes showing a greater increase in the PPC area than non-athletes. As expected, athletes showed a significant reduction in pain perception after HIIT, whereas non-athletes did not. In line, athletes showed a significant decrease in oxyhemoglobin levels in all brain areas post-HIIT, while non-athletes only showed a decrease in sensory motor areas. Interestingly, in athletes, pain reduction correlated with the decrease in PFC oxyhemoglobin during painful stimulation, whereas no significant correlation was observed in non-athletes. The pronounced HIIT-induced increase in oxyhemoglobin in athletes may elevate baseline neural activity to a level where additional activation is limited, potentially reducing the salience of pain-related signals. This athlete-specific response may result from endurance training adaptations, such as enhanced microvascularization and oxygen delivery, promoting greater neural efficiency during high-intensity exercise. These findings highlight HIIT's potential as a targeted pain management strategy for athletes and the need for tailored approaches in non-athletes.

dataset: sub01-sub27 are athletes; sub29-sub53 are non-athletes