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Evidence of central neuroimmune alterations in fibromyalgia: a systematic review of case-control studies
Marçal Castán-Sogas1, Adela Fusté Escolano2
1Department of Clinical Psychology and Psychobiology, Faculty of Psychology, University of Barcelona, Barcelona, Spain; Psychological Services Centre, University of Barcelona, Barcelona, Spain.
Background:
Fibromyalgia (FM) is a chronic disorder characterized by widespread pain, fatigue, and cognitive or affective symptoms. Despite its high prevalence among middle-aged women and substantial clinical impact, the central mechanisms underlying FM remain poorly understood. Evidence points to a multicausal origin, potentially involving the immune system. Although peripheral immune dysregulation has been consistently reported, no systematic review has yet evaluated central neuroimmune changes and their clinical relevance.
Methods:
A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251036797). Searches were performed in PubMed, Web of Science, and Scopus for records published up to January 5, 2025.
Results:
18 studies reporting central immune alterations in FM patients were included. 9 employed neuroimaging techniques, 6 analyzed cerebrospinal fluid, 2 investigated differential gene expression, and one used a translational cellular approach. Despite high heterogeneity across studies and methodologies, findings suggested convergent patterns of glial and neurometabolic abnormalities in cortical and subcortical brain regions, alongside alterations in immune-related proteins and markers of disrupted neuroimmune signaling.
Conclusion:
Consistent with previous reports of peripheral findings, the available evidence suggests that FM may involve central neuroimmune alterations encompassing both pro-inflammatory and regulatory mechanisms across genetic, molecular, and cellular levels. Alterations in brain regions converge on key networks implicated in pain processing, emotional regulation, cognition, and behavior. These findings support a neuroimmune framework for FM and highlight the potential role of neuroimmune processes in its pathophysiology.
