Pain as a precursor: elevated risk of chronic disease development in older adults—findings from dual aging prospective cohort studies and Mendelian randomization analysis

BACKGROUND: The relationship between pain characteristics and chronic disease development in aging populations remains poorly understood. This study explored associations between early pain exposure and incident chronic diseases in older adults through epidemiological and genetic analyses. METHODS: Using data from China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), participants were classified by pain trajectories across consecutive surveys: "now stronger/more sites/more frequent, previously stronger/more sites/more frequent, persistently pain-free, persistently strong/multiple/frequent." Cohorts were followed for incident chronic conditions through 2018 (CHARLS) and 2015 (ELSA). Mendelian randomization (MR) examined causal relationships between multisite chronic pain and disease outcomes. RESULTS: Early pain trajectory changes were significantly associated with increased incidence of multiple chronic diseases. Participants with "persistently strong pain" or "now stronger pain" demonstrated 37%-267% increased disease risks, particularly for chronic lung disease (HR 2.11, 95% CI: 1.52-2.94) and memory-related diseases (HR 3.67, 95% CI: 1.15-11.71); those with "previously stronger pain" remained associated with 24%-124% elevated risks, especially for liver disease (HR 2.24, 95% CI: 1.56-3.22). "Persistently multiple sites" or "now more sites" trajectories were associated with 58%-275% higher risks; "previously more sites" was associated with 39%-203% elevated risks. "Persistently frequent" pain was associated with 62%-131% increased risks. MR confirmed genetic associations between multisite chronic pain and 30 chronic diseases. CONCLUSIONS: The burden of chronic pain in older adults has been underestimated by overlooking its potential association with elevated risks across multiple chronic diseases. Monitoring pain intensity, sites, and frequency should be integrated into geriatric evaluation to promote healthy aging.