Effects of Graded Exposure on Functional Improvement, Quality of Life, and Mental Health in Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic musculoskeletal pain (CMP) is a prevalent and disabling condition associated with impaired physical function and reduced quality of life. Graded exposure therapy (GEP), a cognitive-behavioral intervention targeting pain-related fear and avoidance, has been proposed as a non-pharmacological approach for CMP management. OBJECTIVE: To evaluate the effects of GEP compared with non-GEP interventions in individuals with CMP. METHODS: We searched electronic databases from inception to February 2025 for randomized controlled trials (RCTs) comparing GEP and non-GEP interventions in individuals with CMP. Primary outcomes included pain intensity and pain-related disability. Secondary outcomes included pain-related fear and cognition, health-related quality of life, psychological outcomes, sleep-related outcomes, behavioral adaptation, self-efficacy, and physical functioning. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Eight RCTs involving 554 participants were included. Compared with non-GEP interventions, GEP was associated with improvements in pain-related disability and pain-related fear and cognition, including pain catastrophizing (Pain Catastrophizing Scale [PCS]: mean difference [MD] = -4.45, 95% confidence interval [CI] -7.20 to -1.69) and kinesiophobia (Tampa Scale of Kinesiophobia [TSK]: MD = -4.57, 95% CI -7.11 to -2.03). Disability outcomes have showen beneficial effects across several instruments, although many estimates are based on individual studies. Effects on pain intensity were inconsistent, with significant reductions observed for Neuropathic Pain Scale (NPS) (MD = -2.66, 95% CI -4.09 to -1.23) and Fibromyalgia Impact Questionnaire Pain subscale (FIQ-Pain) (MD = -2.51, 95% CI -3.48 to -1.54). The certainty of evidence ranged from very low to moderate, with most outcomes being downgraded owing to the risk of bias and imprecision. CONCLUSION: GEP may improve pain-related disability and pain-related fear and cognition in individuals with CMP. However, the limited certainty of evidence and variability across populations, interventions, and outcome measures warrant cautious interpretation. Further high-quality trials with standardized outcomes and longer-term follow-up are needed.