Fibromyalgia and Neuroinflammation: Unraveling Pathophysiological Links and Therapeutic Targets

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 2983

Special Issue Editor


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Guest Editor
Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, 31008 Pamplona, Spain
Interests: fibromyalgia; neuroinflammation; central sensitization; glial activation; cytokines; pain modulation; chronic pain; neuroimmune interaction

Special Issue Information

Dear Colleagues,

Fibromyalgia is a complex, chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, cognitive disturbances, and mood disorders. Despite its high prevalence, the pathophysiological underpinnings of fibromyalgia remain incompletely understood. Increasing evidence suggests that neuroinflammation—a process involving the activation of glial cells and the release of pro-inflammatory cytokines within the central nervous system—may play a pivotal role in the sensitization of pain pathways and the development of fibromyalgia symptoms.

This Special Issue aims to explore the emerging connection between fibromyalgia and neuroinflammatory processes. We invite original research articles, comprehensive reviews, and translational studies that investigate the role of neuroinflammation in the pathogenesis, diagnosis, and treatment of fibromyalgia. Topics of interest include, but are not limited to, the following:

  • Microglial and astrocyte activation in fibromyalgia;
  • Cytokine and chemokine profiles in patients with fibromyalgia;
  • Neuroimmune mechanisms underlying central sensitization;
  • Neuroimaging markers of inflammation in fibromyalgia;
  • The gut–brain axis and systemic inflammation in fibromyalgia;
  • Role of oxidative stress and mitochondrial dysfunction;
  • Preclinical models of fibromyalgia with a focus on neuroinflammatory markers;
  • Novel anti-inflammatory therapies targeting neuroimmune pathways;
  • Biomarkers for diagnosis and disease progression;
  • Interplay between neuroinflammation and psychiatric comorbidities.

This Special Issue seeks to foster interdisciplinary collaboration and facilitate the development of novel therapeutic strategies aimed at mitigating neuroinflammatory processes in fibromyalgia. Contributions from neuroscientists, immunologists, rheumatologists, pain specialists, and psychiatrists are highly encouraged.

Dr. Mario García-Domínguez
Guest Editor

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Keywords

  • fibromyalgia
  • neuroinflammation
  • central sensitization
  • glial activation
  • cytokines
  • pain modulation
  • chronic pain
  • neuroimmune interaction

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Published Papers (2 papers)

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Research

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17 pages, 2664 KB  
Article
Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice
by Hung-Yu Huang, Younbyoung Chae, Ming-Chia Lin, I-Han Hsiao, Hsin-Cheng Hsu, Chien-Yi Ho and Yi-Wen Lin
Biomedicines 2026, 14(3), 584; https://doi.org/10.3390/biomedicines14030584 - 5 Mar 2026
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Abstract
Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both for individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to [...] Read more.
Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both for individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to investigate its underlying mechanisms. Programmed cell death ligand 1 (PD-L1)/PD-1 were first identified to be involved in cancer immunotherapy, and their application to pain management has not been yet investigated. Methods: In this study, we aimed to explore the mechanism underlying the action of PD-L1 on the PD-1 pathway in a mouse model of fibromyalgia. Results: We established such a mouse model using intermittent cold stress (ICS) and confirmed mechanical (D4: 2.02 ± 0.13 g, n = 9) and thermal (D4: 4.28 ± 0.21 s, n = 9) hyperalgesia. We found that EA, intracerebral ventricle (ICV) PD-L1 injection, and transient receptor potential vanilloid 1 (Trpv1) knockout effectively counteracted hyperalgesia. We observed low PD-1 expression in the cerebellum of fibromyalgia mice but increased expression of TRPV1 and pain-related kinases. These phenomena could be further reversed by EA, ICV PD-L1 injection, and Trpv1 knockout. To confirm that these effects were caused by PD-L1 release, we added PD-L1-neutralizing antibodies to the EA and PD-L1 treatment. The analgesic effects and EA and PD-L1 mechanisms were inhibited. Conclusions: Our results elucidate the role of the PD-L1/PD-1 pathway in EA treatment of fibromyalgia and reveal its potential value for fibromyalgia management. Full article
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Review

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24 pages, 572 KB  
Review
Moving Toward Objective Diagnosis in Fibromyalgia: Emerging Biomarkers and Digital Phenotyping Tools
by Mario García-Domínguez
Biomedicines 2026, 14(2), 440; https://doi.org/10.3390/biomedicines14020440 - 15 Feb 2026
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Abstract
Fibromyalgia is a complex chronic pain condition characterized by pervasive pain, persistent fatigue, and cognitive disturbances. Despite advances in understanding its neurobiological mechanisms, diagnosis largely relies on subjective symptom assessment and exclusion criteria, contributing to underdiagnosis and treatment delays. Recent research has increasingly [...] Read more.
Fibromyalgia is a complex chronic pain condition characterized by pervasive pain, persistent fatigue, and cognitive disturbances. Despite advances in understanding its neurobiological mechanisms, diagnosis largely relies on subjective symptom assessment and exclusion criteria, contributing to underdiagnosis and treatment delays. Recent research has increasingly focused on identifying objective biomarkers and leveraging digital phenotyping to improve diagnostic precision. Promising biomarkers include neuroimaging indicators of altered pain processing, neuroinflammatory signatures in cerebrospinal fluid and blood, and dysregulated neuroendocrine and autonomic patterns. In addition, metabolomics and transcriptomics have revealed molecular profiles associated with fibromyalgia pathophysiology. Concurrently, digital health tools (e.g., wearable sensors, ecological momentary assessment, and machine learning-based symptom clustering) offer opportunities for continuous, real-world data collection and individualized disease characterization. This body of work suggests that integrating biological and digital metrics could enable a transition from subjective to objective data-driven fibromyalgia classification, facilitating earlier diagnosis and improved therapeutic outcomes. Full article
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