C-reactive protein and incident chronic pain in older adults: comorbidity-driven risk profiles and implications for...

Systemic inflammatory biomarkers such as C-reactive protein (CRP) and interleukin-6 (IL-6) have been implicated in chronic pain, but their independent predictive role in older adults remains unclear. Using longitudinal data from the Health and Retirement Study (2016-2022), we analysed 1850 older adults without chronic pain or arthritis at baseline. CRP, IL-6, IL-10, IGF-1, and the composite INFLA-score, a composite index of low-grade systemic inflammation, were assessed as exposures. Incident chronic pain was defined as the first report of pain during follow-up. Population-averaged Poisson regression models with robust standard errors were used, and sensitivity analyses were conducted in a broader cohort including participants with baseline arthritis. After multivariable adjustment, CRP remained independently associated with incident chronic pain (incidence rate ratio [IRR] 1.10, 95% CI 1.01-1.20), although the effect size was modest. Depression (IRR 1.52, 95% CI 1.23-1.88) and body mass index (IRR 1.02 per unit, 95% CI 1.01-1.04) were stronger predictors. IL-6 was not independently associated in the arthritis-free cohort but showed a small effect in the broader cohort, suggesting context-dependent associations. Incorporating CRP into a clinical prediction model yielded minimal improvement in discrimination (ΔAUC +0.009). IGF-1 showed an inverse association with chronic pain risk in participants without arthritis or obesity. Overall, systemic inflammatory biomarkers appear to contribute limited independent predictive value, while comorbidity burden and psychosocial factors dominate risk. PERSPECTIVE: This study shows that commonly used inflammatory biomarkers offer limited incremental value in predicting chronic pain among older adults. Instead, depression and metabolic factors are the dominant risk factors, supporting a shift towards clinically integrated risk stratification rather than biomarker-based screening alone.