Circadian Regulation and Pain: A Systematic Review of the Association Between Rest-Activity Rhythm and Pain-Related Outcomes.

The rest-activity rhythm (RAR) is a key marker of circadian regulation and is commonly assessed using actigraphy. Emerging evidence suggests that characteristics of RAR, such as amplitude, stability, and regularity, may be associated with pain-related outcomes. However, no systematic review has yet synthesized this evidence across populations and pain conditions. This systematic review aimed to provide an overview of current approaches to measuring and defining RAR and to examine its associations with pain outcomes in both healthy individuals and clinical populations experiencing acute or chronic pain. A systematic search of PubMed, Web of Science, Scopus, and Embase was conducted, with the final search completed on 20 May 2025. Observational studies reporting associations between at least one RAR characteristic and a pain outcome were eligible. Article selection and risk-of-bias assessment using the ROBINS-E tool were performed independently by two reviewers, and findings were synthesized narratively. Seven cross-sectional studies were included, employing diverse analytic methods such as cosinor and non-parametric analyses. Overall, the findings were heterogeneous, suggesting that associations between RAR and pain vary according to the RAR metric used, the analytical approach, and the population studied. Nevertheless, the evidence generally indicates that more robust and well-consolidated circadian rhythms are associated with lower pain, whereas regularity and timing appear to play more context-dependent roles, highlighting the potential relevance of RAR metrics as modifiable targets and the need for standardized measurement approaches.