Passive transfer of fibromyalgia symptoms from patients to mice
Andreas Goebel, … , Camilla I. Svensson, David A. Andersson
Andreas Goebel, … , Camilla I. Svensson, David A. Andersson
Published July 1, 2021
Citation Information: J Clin Invest. 2021;131(13):e144201. https://doi.org/10.1172/JCI144201.
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Research Article Neuroscience

Passive transfer of fibromyalgia symptoms from patients to mice

Abstract

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.

Authors

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

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Figure 2

FMS IgG produces polymodal abnormalities.

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FMS IgG produces polymodal abnormalities. FMS IgG increased the sensitiv...
FMS IgG increased the sensitivity to punctate stimulation with von Frey filaments (A). The threshold for leg withdrawal in response to pressure applied to the thigh (using a Randall-Selitto device) was reduced by FMS IgG compared with HC IgG (B). Female and male mice are affected equally by FMS IgG in the paw-pressure test (C) and the cold-plate test (D). Mechanical hypersensitivity produced by either 1, 2, or 4 injections of 8 mg FMS IgG (E), and by single injections of 2, 4, or 8 mg (F). The front paw grip strength is reduced by FMS IgG compared with HC IgG (G). Data points are mean ± SEM or individual measurements. *P < 0.05, **P < 0.01, ***P < 0.001, FMS IgG compared with HC IgG; 2-way repeated measure ANOVA followed by Sidak’s correction (A, C, D, and G). Data in B were analyzed by unpaired, 2-tailed t test. Data in E and F were compared to the naive preinjection value at time zero by 2-way repeated measure ANOVA followed by Dunnett’s test.