Publications

Journal Article Review Epublish

PubMed: 40649815 DOI: 10.3390/ijms26136036

Pathogenic Crosstalk Between the Peripheral and Central Nervous System in Rheumatic Diseases: Emerging Evidence and Clinical Implications.

Int J Mol Sci 26(13)

Authors: Marino Paroli, Maria Isabella Sirinian

Affiliations

  • Center for Allergology and Immunology, Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Polo Pontino, 04100 Latina, Italy.

Abstract

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment.

MeSH

Cytokines, Pain, Pathology, Central Nervous System, Rheumatic Diseases, Signs And Symptoms, Nervous System