Association of pain sensitization with prefrontal cortex activation and movement patterns during single- and...

Pain sensitization may contribute to heightened prefrontal cortex (PFC) activity during walking in people with knee osteoarthritis (OA), especially under cognitively demanding conditions. We examined associations of central and peripheral pain sensitization with PFC activation and walking performance during single- and dual-task walking. Forty-eight individuals with symptomatic knee OA completed single-task walking (STW) and dual-task walking (DTW) with a serial-7 subtraction. Central and peripheral sensitization were indexed by pressure pain threshold (PPT) at the wrist and knee, respectively. Oxygenated hemoglobin (HbO₂) in bilateral PFC was recorded using functional near-infrared spectroscopy. Gait speed, step duration variability, stride length variability, and serial-7 accuracy were assessed. Linear mixed-effects models tested group (lowest vs highest PPT tertile) by task (STW vs DTW) interactions on HbO₂ and performance, adjusting for age, sex, and BMI. When stratified by wrist PPT, participants (72.9% female, mean age 64.8 ± 7.2 years) showed significant group-by-task interactions for HbO₂ in left dorsolateral PFC (p=0.03, η²p=0.10) and stride length variability (p=0.01, η²p=0.16). When stratified by knee PPT, gait speed showed a significant interaction (p=0.02, η²p=0.11). No other comparisons reached statistical significance. Across walking tasks, the most centrally sensitized group exhibited moderately higher PFC activation (Cohen's d≈0.6-0.7) than the least sensitized group. Central pain sensitization in knee OA is associated with greater recruitment of PFC resources and more variable gait under walking and dual-task conditions. Central sensitization may represent a therapeutic target to reduce executive control demands and improve gait in people with knee OA.