Background: Chronic knee pain is a complex and multifactorial condition influenced not only by structural factors but also by neurophysiological, psychological, and behavioral mechanisms. Central sensitization and fear of movement are important contributors to pain persistence, functional limitations, and reduced participation in daily and physical activities. Exercise therapy, as a primary rehabilitation intervention, may influence these mechanisms through various neural, biological, and psychological pathways.

Objective: This narrative review aimed to explore the underlying mechanisms through which exercise interventions affect central sensitization and fear of movement in individuals with chronic knee pain and to provide an integrated perspective for clinical application.

Methods: Relevant studies investigating the effects of exercise interventions on chronic knee pain, central sensitization, pain processing, psychological factors related to pain, and fear of movement were reviewed and critically discussed. Current evidence regarding neural, biological, and psychological mechanisms involved in exercise-induced pain modulation and movement adaptation was synthesized.

Results: Current evidence suggests that graded and individualized exercise interventions may improve clinical outcomes through multiple mechanisms, including enhanced endogenous pain modulation, increased tolerance to mechanical loading, reduction of threat-related responses to movement, modification of maladaptive pain beliefs, and improvement of self-efficacy. In individuals presenting with features of central sensitization and fear of movement, integrating pain neuroscience education with exercise therapy may provide additional benefits compared with exercise alone.

Conclusion: Management of chronic knee pain should move beyond purely structural approaches toward multidimensional and patient-centered strategies. Assessment of central sensitization and psychological factors before treatment initiation may facilitate more targeted exercise prescription. Future research should focus on personalized exercise approaches, identification of predictors of treatment response, and high-quality longitudinal clinical trials.