Molecular and clinical markers of pain relief in complex regional pain syndrome: An observational study

Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. While long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies.In this study, we characterised CRPS patients over a course of 2.5 years of standard treatment. Patient underwent clinical examination including pain measurement, symptom questionnaires, Quantitative Sensory Testing (QST) and blood sampling. Exosomal microRNA levels were measured via qPCR. After follow-up, patients were stratified into "pain relief" (mean pain reduced by ≥ 2 numeric rating scale) or "persistence" (mean pain unchanged or worsened). Primary outcome was miR-223 and miR-939 expression, secondary outcomes were differences in clinical parameters between groups and time points.39 patients were included, 33 of whom qualified for stratification. Overall, patients reported lower pain and improved clinical characteristics after 2.5 years, but no significant changes in QST or miR-223 and miR-939 expression levels. 16 patients met criteria for pain relief. This was associated with stable exosomal miR-223 expression, while levels further decreased in pain persistence. Clinically, pain relief was marked by shorter disease duration and correlated positively with high initial pain.We identified progressively reduced miR-223 as putative biomarker of chronic CRPS pain. Clinically, this study underlines the importance of early diagnosis and treatment showing that high initial pain does not predict unfavourable outcome. Finally, pain relief and recovery of sensory disturbances seem independent processes.