A Biomarker-Based Framework for the Prediction of Future Chronic Pain

Chronic pain is a multifactorial condition presenting significant diagnostic and prognostic challenges. Biomarkers for the classification and the prediction of chronic pain are therefore critically needed. In this multi-dataset study of over 523,000 participants, we applied machine learning to multi-dimensional biological data from the UK Biobank to identify biomarkers for 35 medical conditions associated with pain (e.g., clinical diagnosis of rheumatoid arthritis, fibromyalgia, stroke, gout, etc.) or self-reported chronic pain (e.g., back pain, knee pain, etc). Biomarkers derived from blood immunoassays, brain and bone imaging, and genetics were effective in predicting medical conditions associated with chronic pain (area under the curve (AUC) 0.62-0.87) but not self-reported pain (AUC 0.50-0.62). Among the biomarkers identified was a composite blood-based signature that predicted the onset of various medical conditions approximately nine years in advance (AUC 0.59-0.72). Notably, all biomarkers worked in synergy with psychosocial factors, accurately predicting both medical conditions (AUC 0.69- 0.91) and self-report pain (AUC 0.71-0.92). Over a period of 15 years, individuals scoring high on both biomarkers and psychosocial risk factors had twice the cumulative incidence of diagnoses for pain-associated medical conditions (Hazard Ratio (HR): 2.26) compared to individuals scoring high on biomarkers but low on psychosocial risk factors (HR: 1.06). In summary, we identified various biomarkers for chronic pain conditions and showed that their predictive efficacy heavily depended on psychological and social influences. These findings underscore the necessity of adopting a holistic approach in the development of biomarkers to enhance their clinical utility.