Systemic inflammation mediates links between sleep, obesity, and musculoskeletal pain but not consistently for psychological factors.

A range of studies have shown that psychological and lifestyle factors are associated with musculoskeletal pain. The factors also correlate with persistent systemic inflammation. Since systemic inflammation is also present in numerous conditions involving musculoskeletal pain, it is of interest to examine whether systemic inflammation mediates the relationship between psychological and lifestyle factors and musculoskeletal pain. A systematic review was conducted according to the PRISMA guidelines. The PubMed, Scopus and PsycINFO databases were searched for studies examining systemic inflammation as a mediating factor between psychological and/or lifestyle factors and musculoskeletal pain. Studies were grouped into three themes of influencing factors; sleep disturbances, obesity and psychological factors. A risk of bias assessment tool for mediation studies was used to assess methodological quality. A narrative synthesis of outcomes was performed. Twenty-one articles were included in the review. Evidence derived primarily from moderate-quality studies suggested small but significant mediating effects of systemic inflammation on the relationship between sleep disturbance and musculoskeletal pain, as well as between obesity and osteoarthritis. In contrast, no consistent mediating effects were observed for psychological factors. However, findings from studies of low to moderate quality indicated potential interaction effects, suggesting that psychological factors may lead to pain in the presence of systemic inflammation. Systemic inflammation may represent a biological pathway linking sleep disturbances and obesity to musculoskeletal pain, likely operating alongside other mediating factors. For psychological factors, systemic inflammation appears to act as an interacting variable rather than a direct mediator of pain. Given the reliance on cross-sectional data in current research, longitudinal studies are essential to confirm these causal mechanisms and to evaluate the clinical significance of targeting systemic inflammation in pain management.