The Neutrophil-to-Lymphocyte Ratio in Fibromyalgia: A Systematic Review with a Neuroimmune Perspective

Background/Objectives. Alterations in systemic immune balance, reflected by changes in neutrophil and lymphocyte proportions, index a peripheral immune state relevant to central nervous system function. This systematic review and meta-analysis aimed to assess the differences in the neutrophil-to-lymphocyte ratio (NLR) between fibromyalgia patients and healthy controls and offer a framework to study fibromyalgia. Methods. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered our work on PROSPERO (CRD420251001424). Two authors performed a comprehensive search of databases, including PubMed, Embase, Web of Science, and Scopus, until August 2025. The Newcastle–Ottawa Scale (NOS) was used for bias risk assessment, and STATA 19.0 software was used for statistical analyses. The standardized mean difference (SMD) and 95% confidence interval (CI) of the NLR were reported. Finally, 24 studies with 3143 fibromyalgia patients and 1610 healthy controls were included in our meta-analysis. Results. The results indicated that patients with fibromyalgia had elevated NLRs compared to healthy controls (SMD = 0.30; 95% CI = 0.07–0.52; p = 0.01). Our results showed no publication bias. A bivariate random-effects meta-analysis on the diagnostic accuracy of the NLR showed a summary sensitivity of 0.74 (95% CI: 0.62–0.83) and a summary specificity of 0.63 (95% CI: 0.51–0.73). Conclusions. Our meta-analysis supports the fact that the NLR is significantly different between patients with fibromyalgia and healthy controls. We conceptualize the idea that the NLR may be used as a “state-dependent” peripheral marker indexing the susceptibility of central nervous system sensitization, pain amplification, and responsiveness to future therapies.