Post-Treatment Urine Metabolites as Indicators of Chronic Pain: A Secondary Data Analysis of a Pragmatic Clinical Trial

Abstract

Biomarkers may complement patient-reported outcomes by providing objective insight into the multidimensional nature of chronic pain. The urine metabolite pain indicator (UMPI), a composite of four urine metabolites, has previously demonstrated cross-sectional associations with pain-related symptoms; however, it is unclear whether these associations are consistent over time. This study evaluated whether the UMPI and its individual metabolites remain associated with chronic pain outcomes following intervention, which would support its potential as a monitoring biomarker. A secondary analysis of a pragmatic clinical trial, where 148 active-duty service members with chronic pain provided urine samples and completed 11 self-reported outcome measures at baseline and 6-week follow-up after either a complementary and integrative health or a standard rehabilitative care pain intervention. Associations were examined using linear regression and mixed models. The UMPI remained significantly associated with physical function and overall pain impact post-intervention. Ethylmalonic acid showed associations with fatigue, anger, and physical function. Notably, methylmalonate, while not significant at baseline, had the most robust association with pain post-intervention, including significant correlations with both physical function and pain impact. Kynurenic acid was associated with sleep-related impairment. Pyroglutamic acid showed no significant adjusted associations. No statistically significant differences in metabolite and symptom correlations were found between time points, suggesting that these associations remained consistent over the short term. The UMPI may serve as a reliable, noninvasive index biomarker for tracking chronic pain burden, particularly physical outcomes. Findings support integrating the UMPI into biologically informed chronic pain assessment.