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 9

FMS IgG binds to satellite glial cells and to neurons in vitro.

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FMS IgG binds to satellite glial cells and to neurons in vitro. Live cel...
Live cells were incubated with FMS IgG or HC IgG to examine only cell surface binding. In satellite glial cell (SGC) cultures (A), FMS IgG labeled a greater percentage of cells than HC IgG when analyzed per animal (B) and by the total number cells (C). The immunoreactivity, analyzed as signal intensity (integrated density), was higher in cells incubated with FMS IgG than HC IgG (D). FMS IgG labeled SGCs (GS+) and non-SGCs (GS–) to a greater extent (percentage, E) and with a higher intensity (F) than HC IgG. FMS and HC IgG labeling of neuronal cultures (G) was not different when considering the percentage of cells labeled per animal (H), but a difference was observed when the total number of cells was considered (I). The signal intensity was higher for cells exposed to FMS IgG than HC IgG (J). FMS IgG labeled neurons (βIII-tubulin+) and non-neurons (βIII-tubulin–) to a greater extent than HC IgG (K). The signal intensity of FMS IgG binding to neurons was greater than FMS IgG binding to non-neuronal cells and HC IgG binding to all cells (L). FMS IgG and IB4 colocalization (M) indicates that FMS IgG binds neuronal cell membranes. All scale bars: 20 μm. Data points are the percentage of cells bound by HC or FMS IgG (B and H). In D, F, J, and L data points are the integrated density of individual cells across 3 experiments. Bar and whiskers indicate mean ± SEM (n = 3 individual experiments). *P < 0.05; ***P < 0.001 by unpaired t test (B, D, H, and J), χ2 test (C, E, I, and K), or Kruskal-Wallis test with Dunn’s post hoc test (F and L).