99: Fibromyalgia gut microbiota stimulates the generation of pain-inducing IgG in mice

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, , , , , , Neuroimmunology, , ,

Background and Aims: Introduction: We previously identified a role for pain-inducing IgG autoantibodies in fibromyalgia (FM), but why these autoantibodies develop remains unclear. The gut microbiome of FM patients is altered, and the fecal microbiota transfers (FMT) of FM stool samples into germ free mice induce pain. Our hypothesis is that pain-indcuing FM autoantibodies develop through cross-reactivity with gut bacteria. Here, we will determine how the FM gut microbiome drives an adaptive immune response that leads to pain-inducing autoantibodies in mice.

Methods: Methods: FMTs into germ-free mice were performed with FM or healthy control (HC) stool samples (1 human stool sample/group/experiment). Four weeks after FMT, serum was collected, mouse gut IgG+ plasma cells were quantified using flow cytometry and IgG accumulation in the dorsal root ganglia (DRG) was analyzed with immunofluorescent staining (N=5/group/sex). IgG was purified from the collected serum of germ-free mice and intrathecally injected into specific pathogen free mice. Mechanical sensitivity and the mouse grimace scale were used to evaluate IgG-induced pain behaviour. Accumulation of injected IgG in the DRG was quantified (N=11-13/group).

Results: Results: FM microbiota transfer increased IgG+ plasma cells in the small intestinal lamina propria and increased IgG accumulation in the DRG. IgG transfer from mice receiving FM FMT into naïve mice induced mechanical hypersensitivity and spontaneous pain, but HC IgG did not. Transferred FM IgG accumulated in the DRG compared to HC IgG.

Conclusions: Conclusion: These results suggest that FM patients’ altered gut microbiome stimulates abnormal local and systemic immune responses that generate pain-inducing IgG in mice.

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Krock, E. et al. Fibromyalgia patients with elevated levels of anti–satellite glia cell immunoglobulin G antibodies present with more severe symptoms. Pain 164, 1828–1840 (2023). 
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Presenting Author: Hannah Cho
Submitting Author: Hannah Cho

Senior Author: Emerson Krock

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Allutas Alhamwi - McGill University
• Clara MacMahon - McGill University
• Alexander Rosenström - Uppsala University
• Ezrah Issac Roy - McGill University
• Caroline Monat - McGill University
• Karolina af Ekenstam - Karolinska Institutet
• Monika Löfgren - Karolinska Institutet
• Emilie Linderoth - Karolinska Institutet
• Katalin Sandor - Karolinska Institutet
• Benoit Cousineau - McGill University
• Jeffrey S. Mogil - McGill University
• Camilla I. Svensson - Karolinska Institutet
• Eva Kosek - Karolinska Institutet, Uppsala University
• Irah King - McGill University
• Emerson Krock - McGill University