ArticleMolecular pain
Whole-blood miRNA candidate prioritization for longitudinal pain change suggests synaptic and neuronal organization pathway involvement in early rheumatoid arthritis.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Pain is a major clinical outcome in chronic inflammatory disease, yet molecular correlates of within-person pain change remain unclear and must be distinguished from inflammatory change. We used longitudinal whole-blood multi-omics data from the RA-MAP/TACERA early rheumatoid arthritis cohort to prioritize microRNA (miRNA) candidates whose 6-month changes co-varied with change in visual analogue scale pain (ΔVAS). Among 151 participants and 1,881 miRNA features, we applied a stability-oriented delta-omics workflow combining subsampling elastic-net selection frequency, bootstrap directional filtering, and post-selection rank-residual partial correlation adjusted for ΔCRP and ΔESR. This identified 29 directionally stable miRNA candidates; after ΔCRP/ΔESR adjustment, 16 retained sign-consistent support at post-selection BH-FDR < 0.05 within these 29 candidates. Matched miRNA-mRNA delta analysis found no individual miRNA-mRNA pair surviving pair-level BH-FDR correction. At the primary nominal pair-selection threshold of p < 0.05, 123 inverse pairs involving 117 target genes yielded exploratory Gene Ontology Biological Process enrichment involving synaptic and neuronal organization; however, no GO term remained BH-significant when the pair-selection threshold was tightened to p < 0.01. The exploratory plasma chronic neck pain comparison yielded 22 of 39 sign-consistent assay matches (56.4%; exact 95% CI, 39.6%-72.2%), which was not statistically distinguishable from the 50% chance expectation, and no match survived BH-FDR correction. These findings outline a stability-oriented, inflammation-adjusted approach for prioritizing blood miRNA candidates linked to pain change. The 16-miRNA subset should be interpreted as a hypothesis-generating candidate pool rather than a validated biomarker panel and provides a focused basis for future longitudinal validation and functional studies.
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