Journal Article

Passive transfer of fibromyalgia symptoms from patients to mice

Gentry, Clive, Krock, Emerson, Kadetoff, Diana, Maurer, Margot, Svensson, Camilla I., Goebel, Andreas, Urbina, Carlos Morado, Tour, Jeanette, Baharpoor, Azar, Andersson, David A., Menezes, Joana, Cuhadar, Ulku, Sandström, Angelica, Kosek, Eva, Jurczak, Alexandra, Sensi, Serena, Bevan, Stuart, Israel, Mathilde R., Vastani, Nisha, Nomura, Yuki, Sandor, Katalin, Haglund, Lisbet, Brieskorn, Louisa

2021

Overview

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.

• Publisher: American Society for Clinical Investigation
• Subject: Animals / Biomedical research / Case-Control Studies / Cold / Development and progression / Disease Models, Animal / Dorsal root ganglia / Drug dosages / Endothelial cells / Etiology / Experiments / Female / Females / Fibromyalgia / Fibromyalgia - etiology / Fibromyalgia - immunology / Fibromyalgia - physiopathology / Ganglia, Spinal - physiopathology / Glial cells / Health aspects / Humans / Hypersensitivity / Immunization, Passive / Immunoglobulin G / Immunoglobulin G - administration & dosage / Immunoglobulin G - blood / Innervation / Localization / Locomotor activity / Macrophages / Male / Mechanical stimuli / Mice / Mice, Inbred C57BL / Neuronal-glial interactions / Nociceptors - immunology / Nociceptors - physiology / Pain / Pain - physiopathology / Pain perception / Pain Threshold - physiology / Pathophysiology / Patients / Physiological aspects / Sensory neurons / Spinal cord