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Updated: Jun 13, 2026

A Randomized, Sham-Controlled Trial of Cranial Electrical Stimulation for Fibromyalgia Pain and Physical Function, Using Brain Imaging Biomarkers
Published on: January 5, 2024
Neuroendocrine immunology of fibromyalgia
Manuela Di Franco1, Cristina Iannuccelli, Guido Valesini
1Department of Clinical and Medical Therapy, Rheumatology Unit, Sapienza University of Rome, Rome, Italy. manuela.difranco@uniroma1.it
Abstract:
The pathophysiology of fibromyalgia (FM) is not completely understood. The disease is characterized by a central sensitization with an amplification of pain perception. A combination of interactions among external stressors, behavioral constructs, neurotransmitters, hormones, immune, and sympathetic nervous systems appears to be involved. It is known that the neuroimmunoendocrine system has a role in the pathogenesis of the disease and multiple abnormalities have been demonstrated in the peripheral and central nervous systems. Bidirectional mechanisms involving peripheral nociceptive input as well as abnormal central pain processing are involved. Hypothalamic-pituitary-adrenal axis alterations have also been shown with abnormal response to stress. Recent data highlight the putative role of cytokines in the pathogenesis of FM. The autonomic nervous system is implicated in the maintenance of the physiological homeostasis and sympathetic activity appears increased in FM. Neuropeptide Y and its receptors Y1 and Y2 seem to have a complex role in pain modulation.
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