Abnormal Brain Structure and Function in People with Shoulder Pain: A Systematic Review of Neuroimaging Studies

Background: Shoulder pain (SP) is a prevalent musculoskeletal disorder. Emerging evidence suggests maladaptive brain plasticity in individuals with SP. This systematic review summarized structural and functional brain abnormalities in individuals with SP and explored their associations with clinical outcomes. Methods: PubMed, Web of Science, EBSCO, and EMBASE were searched from inception to June 2025. The risk of bias was assessed using JBI checklist, and the evidence was graded using the GRADE approach. Results: Five cross-sectional studies were included. These studies demonstrated low to moderate risk of bias. Individuals with SP demonstrated lower volume and density of thalamus grey matter compared to healthy controls. Besides, lower grey matter (volume, density or thickness) was observed in regions such as the amygdala, prefrontal, postcentral, and temporal cortices. Functional neuroimaging studies reported both increased and decreased functional connectivity, as well as abnormalities in regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) in brain areas including thalamus, prefrontal, anterior cingulate, middle temporal, orbitofrontal, and sensorimotor cortices. These structural and functional brain changes were associated with higher pain intensity, lower pain threshold, longer pain duration, poor shoulder function and psychological outcomes. However, the overall certainty of evidence was rated as very low due to the small number of studies and methodological heterogeneity. Conclusion: This systematic review provides preliminary, hypothesis-generating evidence on brain abnormalities in individuals with SP. Very low-certainty evidence suggests that SP may be associated with structural and functional abnormalities in brain regions involved in pain processing, emotion, and sensorimotor integration. Further longitudinal studies are needed to validate the findings.