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

## TL;DR

This review explores how neuroinflammatory biomarkers could help identify and treat chronic low back pain patients with central sensitization.

## Contribution

The paper provides a critical evaluation of neuroinflammatory biomarkers in CLBP and their potential for patient stratification.

## Key findings

- Neuroinflammatory processes are linked to subgroups of CLBP patients, supported by TSPO-PET imaging and CSF chemokine studies.
- Epigenetic markers like BDNF DNA methylation correlate with central sensitization-related pain.
- Traditional systemic inflammatory markers are inconsistent and nonspecific in CLBP.

## Abstract

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. Studies were preferentially selected according to the following hierarchical criteria: (1) human studies directly investigating neuroinflammatory biomarkers in CLBP; (2) mechanistic human imaging or cerebrospinal fluid studies; (3) translational preclinical investigations providing direct mechanistic relevance; and (4) high-quality systematic reviews providing synthesis of biomarker evidence. As this was a narrative review, study selection was guided by conceptual relevance and translational significance rather than by formal systematic review methodology. 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 phenotyping to establish clinical utility.