Most running studies have considered level running (LR), yet the regulation of locomotor behaviour during uphill (UR) and downhill (DR) running is fundamental to increase our understanding of human locomotion. The purpose of this article was to review the existing literature regarding biomechanical, neuromuscular and physiological adaptations during graded running. Relative to LR, UR is characterized by a higher step frequency, increased internal mechanical work, shorter swing/aerial phase duration, and greater duty factor, while DR is characterized by increased aerial time, reduced step frequency and decreased duty factor. Grade also modifies foot strike patterns, with a progressive adoption of a mid- to fore-foot strike pattern during UR, and rear-foot strike patterns during DR. In UR, lower limb muscles perform a higher net mechanical work compared to LR and DR to increase the body's potential energy. In DR, energy dissipation is generally prevalent compared to energy generation. The increased demands for work as running incline increases are met by an increase in power output at all joints, particularly the hip. This implies that UR requires greater muscular activity compared to LR and DR. Energy cost of running (C ) linearly increases with positive slope but C of DR decreases until a minimum slope is reached at -20 %, after which C increases again. The effects of slope on biomechanics, muscle contraction patterns and physiological responses have important implications for injury prevention and success of athletes engaged in graded running competitions.

CD patients in clinical remission have decreased muscle function that may affect their quality of life. This pattern is reflected by reduced strength and endurance indexes, particularly for lower limbs. The reasons for these changes need further study. Strength training should be assessed in these patients.

Scientific experiments on running mainly consider level running. However, the magnitude and etiology of fatigue depend on the exercise under consideration, particularly the predominant type of contraction, which differs between level, uphill, and downhill running. The purpose of this review is to comprehensively summarize the neurophysiological and biomechanical changes due to fatigue in graded running. When comparing prolonged hilly running (i.e., a combination of uphill and downhill running) to level running, it is found that (1) the general shape of the neuromuscular fatigue-exercise duration curve as well as the etiology of fatigue in knee extensor and plantar flexor muscles are similar and (2) the biomechanical consequences are also relatively comparable, suggesting that duration rather than elevation changes affects neuromuscular function and running patterns. However, 'pure' uphill or downhill running has several fatigue-related intrinsic features compared with the level running. Downhill running induces severe lower limb tissue damage, indirectly evidenced by massive increases in plasma creatine kinase/myoglobin concentration or inflammatory markers. In addition, low-frequency fatigue (i.e., excitation-contraction coupling failure) is systematically observed after downhill running, although it has also been found in high-intensity uphill running for different reasons. Indeed, low-frequency fatigue in downhill running is attributed to mechanical stress at the interface sarcoplasmic reticulum/T-tubule, while the inorganic phosphate accumulation probably plays a central role in intense uphill running. Other fatigue-related specificities of graded running such as strategies to minimize the deleterious effects of downhill running on muscle function, the difference of energy cost versus heat storage or muscle activity changes in downhill, level, and uphill running are also discussed.