Passive transfer of fibromyalgia symptoms from patients to mice.

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

doi:10.1172/jci144201

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.

Highlights

Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain, augmented pain sensitivity to mechanical pressure and cold temperatures [1,2,3,4], as well as fatigue and emotional distress [5,6,7]
IgG purified from the serum of individual FMS patients and healthy control (HC) subjects recruited from the Walton Centre (Liverpool, United Kingdom [UK]) was administered to female mice by intraperitoneal injection for 4 consecutive days (8 mg per day)
The observed hypersensitivities produced by IgG preparations from different FMS patients showed similar amplitudes and time courses

Summary

Introduction

Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain, augmented pain sensitivity to mechanical pressure and cold temperatures [1,2,3,4], as well as fatigue and emotional distress [5,6,7]. The prevalence of FMS is at least 2% [8], and approximately 80% of FMS patients are women. The prevalence rises to 10%–30% among patients diagnosed with autoimmune rheumatological conditions [9, 10], and FMS is one of the most common chronic pain conditions. The etiology and pathophysiology of FMS are not completely understood [11] and the current treatment strategies for FMS rely mainly on lifestyle changes, physical exercise, and drug therapy with antidepressants and anticonvulsants. The development of novel, mechanism-based therapies has been hampered by the limited understanding of the basis of FMS

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Conclusion