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CRP is independently linked to incident chronic pain in older adults, but adding it to clinical risk prediction produces only a minimal gain. Depression and BMI show a stronger association with future chronic pain, placing the predictive value of systemic inflammatory biomarkers.
Systemic inflammation has been investigated as a potential marker of chronic pain risk, but whether inflammatory biomarkers can meaningfully identify older adults who will develop chronic pain remains uncertain.
Researchers addressed this question using longitudinal Health and Retirement Study (HRS) data collected from 2016 to 2022. The primary analysis included 1,850 older adults who had neither chronic pain nor arthritis at baseline. C-reactive protein (CRP), interleukin (IL)-6, IL-10, insulin-like growth factor-1 (IGF-1), and the composite INFLA-score—a validated measure incorporating CRP, leukocyte and platelet counts, and the granulocyte-to-lymphocyte ratio—were evaluated for their association with incident chronic pain, defined as the first occurrence of pain during follow-up.
After adjustment for multiple factors, CRP retained an association with incident chronic pain, with an IRR of 1.10. The magnitude of this association was modest. Two clinical characteristics showed stronger associations. Depression had an IRR of 1.52, while body mass index was associated with a 2% increase in incidence rate per unit increase in body mass index (BMI; incidence rate ratio 1.02). This difference in effect size is important because a biomarker can retain an independent statistical association without necessarily adding substantial value to clinical risk prediction.
The practical predictive contribution of CRP was limited. When CRP was incorporated into a clinical prediction model, the area under the curve increased by only 0.009, indicating minimal improvement in discrimination. The results therefore distinguished between association and predictive utility: although CRP remains statistically associated with incident chronic pain, its addition does little to improve the ability of the model to discriminate future cases. The findings were not uniform across all inflammatory markers or clinical groups.
In the cohort without arthritis, IL-6 was not independently linked with incident chronic pain. A small connection emerged in the broader sensitivity analysis that included participants with baseline arthritis, indicating that the relationship between IL-6 and chronic pain differs according to the underlying clinical population. IGF-1 illustrated an inverse link with chronic pain risk among those without arthritis or obesity.
The findings indicated that commonly assessed inflammatory biomarkers have limited independent predictive value for chronic pain in older adults, despite CRP retaining a modest association with incident disease. The study instead points to the importance of considering psychosocial and metabolic characteristics alongside biological markers when assessing chronic pain risk.
The Journal of Pain
C-reactive protein and incident chronic pain in older adults: comorbidity-driven risk profiles and implications for preventive screening
Lavinia Rech et al.
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