Neuroinflammatory Biomarkers in Chronic Low Back Pain: Mechanisms, Clinical Evidence, and Translational Challenges

Background: Chronic low back pain (CLBP) is a leading cause of disability worldwide and remains clinically challenging due to its marked heterogeneity and limited correlation between structural pathology and symptoms. Increasing evidence suggests that neuroinflammatory mechanisms and central sensitization (CS) contribute to pain persistence in a clinically relevant subset of patients. This narrative review critically evaluates the current evidence on neuroinflammatory biomarkers in CLBP and discusses their translational potential for mechanism-based patient stratification. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar using terms related to neuroinflammation, biomarkers, CLBP, CS, and glial activation. Priority was given to human studies, systematic reviews, and mechanistic investigations. Results: Converging evidence supports the involvement of neuroinflammatory processes in subgroups of patients with CLBP. In vivo TSPO-PET imaging and experimental data support glial activation in pain-processing regions. Cerebrospinal fluid studies report elevated chemokines, particularly interleukin-8 and monocyte chemoattractant protein-1, highlighting periphery-to-central nervous system inflammatory cross-talk and the concept of compartmentalized neuroinflammation. In parallel, epigenetic markers such as brain-derived neurotrophic factor DNA methylation have emerged as indirect correlates of CS-related pain phenotypes. In contrast, traditional systemic inflammatory markers show inconsistent and nonspecific associations. Conclusions: Neuroinflammatory biomarkers hold promise for mechanism-based stratification of CLBP, particularly for identifying patients with CS-driven pain. However, major methodological and translational challenges remain, including lack of standardization, limited accessibility of central nervous system-compartment measures, and the need for longitudinal and interventional validation. Future research should prioritize multi-marker and multi-compartment approaches integrated with functional pheno-typing to establish clinical utility.