INTRODUCTION: Altered walking patterns in individuals with knee osteoarthritis (OA) are a key driver of disease; however, mechanisms underlying this relationship are not clear. Central sensitization is now recognized as an important contributor to pain experience in people with knee OA. In the presence of chronic pain and central sensitization, there are alterations in activity and connectivity across multiple brain regions (e.g., prefrontal cortex, primary motor cortex) that could influence dynamic control of gait. However, the association of central sensitization with gait patterns in knee OA has not been studied. Our objective was to investigate whether central sensitization in individuals with knee OA is associated with dynamic control of gait as assessed using wearable sensor-derived measures of gait complexity and dynamic stability. We hypothesized that a greater degree of sensitization would be associated with lower gait complexity and stability. METHODS: We used data from the 12th-year visit of the Multicenter Osteoarthritis Study, a longitudinal cohort study of individuals with and without knee OA. This was the first visit at which the relevant gait parameters were collected using wearable sensors. Individuals from this visit with valid data available for all measures contained in this analysis were included. Mechanical temporal summation (TS), an augmented response to repetitive mechanical stimulation, is a reliable and valid measure of central sensitization. To assess TS, participants’ pain ratings were assessed after a single wrist stimulus was applied with successively weighted probes until a pain rating of at least 4/10 was achieved (the highest weighted probe was used if that pain rating was not obtained), then was assessed again after 10 repeated stimuli at a rate of 1 Hz was applied with the same probe. A post-stimulation pain rating larger than the initial pain rating reflected facilitated TS. For gait analyses, participants completed 2 trials of a 20m walking test at their usual walking pace while wearing inertial sensors on their lower back and both feet. The lower back sensor was used to calculate sample entropy and Lyapunov exponent, both of which may provide a window into how dynamic control of gait is altered in disease. Sample entropy measures the inter-stride predictability or regularity of gait kinematics. Lower sample entropy represents a more regular or predictable (i.e., less complex) gait pattern and may reflect a reduced ability of the neuromotor system to adapt to ongoing changes experienced in daily walking. LE measures the inter-stride stability of gait kinematics. Large LE values represent more gait instability and may reflect a reduced ability of the motor system to recover from small perturbations. We averaged the gait outcomes across the two trials. Exposure variables were standardized. We determined the association between TS and gait parameters using linear regression while adjusting for age, sex, race, body mass index (BMI), depressive symptoms, education, and presence of radiographic knee OA. Analyses were not adjusted for pain or gait speed because we hypothesized that these impairments were on the causal pathway between our exposure and outcomes. RESULTS: Data from 2,179 participants (age = 62.4 ± 10.0 years, BMI = 29.1 ± 5.5 kg/m2, 56.3% female) were included in the analysis. One standard deviation (SD) increase in TS was associated with a -0.024 [95% Confidence intervals -0.038, -0.010] change in sample entropy (i.e., more regular gait) but not with a change in LE (-0.002 [95% Confidence intervals -0.008, 0.004]). CONCLUSION: Individuals with knee OA and central sensitization display a less complex or more predictable gait pattern, evidenced by lower sample entropy, likely reflecting a deterioration in dynamic control of gait. However, central sensitization was not associated with an individual’s ability to respond to natural fluctuations that occur in walking, as evidenced by a lack of association with LE. We propose a plausible mechanism in which central sensitization may cause a reduction in gait complexity via continuous nociceptor release of glutamate, NMDAR activation, and changes in motoneuron excitability and inhibition at multiple sites along the motor pathway. Although causality cannot be determined from this cross-sectional study, these findings provide support for an association between central sensitization and specific aspects of the walking pattern in people with knee OA. Interventions to mitigate central sensitization may be useful to improve gait quality in people with knee OA.