Relative differences of brain, sensory, psychological, motor, and tissue domains across musculoskeletal pain conditions: Systematic review and multivariate meta-analyses.

Musculoskeletal pain is associated with alterations across brain, sensory, psychological, motor, and tissue domains, but the relative magnitude of these differences across domains and diagnoses remains unclear. We synthesised evidence comparing people with fibromyalgia, knee osteoarthritis, low back pain, and neck pain with pain-free controls and examined whether multidomain patterns differed by diagnosis. MEDLINE, EMBASE, PsycINFO, CINAHL, and SPORTDiscus were searched from inception to June 2025, supplemented by trial registries and reference lists. We included observational studies and randomised trials contributing baseline data that compared adults with fibromyalgia, knee osteoarthritis, low back pain, or neck pain with pain-free controls. Standardised mean differences (Hedges' g) were pooled using random-effects models with robust variance estimation. Multivariate models jointly estimated domain-level effects while accounting for within-study dependence. Certainty of evidence was assessed using GRADE. Across 118 studies (N = 11,822), psychological (g = 1.08, 95% CI 0.94-1.22; moderate-certainty evidence) and sensory (g = 0.85, 95% CI 0.61-1.08; moderate-certainty evidence) measures showed larger case-control differences than motor (g = 0.66, 95% CI 0.51-0.82; very low-certainty evidence), brain (g = 0.59, 95% CI 0.39-0.78; low-certainty evidence), and tissue measures (g = 0.30, 95% CI 0.05-0.55; very low-certainty evidence). Patterns of effects differed across diagnostic categories, with fibromyalgia showing larger differences across domains than the other conditions. PERSPECTIVE: This review provides an integrated overview of evidence that has often been restricted to single domains or diagnoses. Considering findings across multiple assessment domains may help distinguish musculoskeletal pain states and guide future multidomain research and more targeted treatment approaches. REGISTRATION: This review was prospectively registered on the Open Science Framework (https://osf.io/dy9ek).