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Mechanical sensitization of sensory afferents after passive transfer of fibromyalgia IgG

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The Journal of Physiology

Published online on

Abstract

["The Journal of Physiology, EarlyView. ", "\nAbstract figure legend In addition to widespread pain and fatigue, people with fibromyalgia (FM) experience sensory abnormalities and report lingering, painful sensations after touch or mechanical probing of the skin. Administration of IgG purified from FM patients to mice transfers symptoms and signs of FM. Here, we have examined whether sensory afferents in skin‐saphenous nerve preparation from mice injected with FM patient IgG displayed ongoing firing after mechanical stimulation. This analysis revealed that C‐mechano (CM) and Aδ‐ mechano (AδM) afferents innervating the skin in FM‐IgG treated mice fired significantly more action potentials after, but not during, application of mechanical force steps compared to, afferents in preparations from mice treated with healthy control (HC)‐IgG. This sustained evoked activity mirrors the nociceptor hyperexcitability observed in people with FM, strongly suggesting that autoreactive IgG is responsible for this phenomenon in patients.\n\n\n\n\n\n\n\n\n\nAbstract\nFibromyalgia (FM) is a chronic pain disorder with a severe impact on a person's health‐related quality of life. In addition to the characteristic widespread pain and fatigue, people with FM regularly experience sensory abnormalities and report lingering, often painful sensations after mechanical probing of the skin. The neurobiological changes which underlie the varied symptoms in FM are incompletely understood, but many symptoms and signs can be transferred from patients to mice by administration of patient IgG. The present study aimed to explore whether sensory afferents, including nociceptors, in rodents injected with FM patient IgG displayed ongoing firing after mechanical stimulation. Skin saphenous nerve recordings were retrospectively analyzed to assess the presence and quality of ongoing discharges following mechanical stimulation of sensory afferents in mouse skin after passive‐transfer of FM patient IgG. Our analysis revealed that C‐mechano and Aδ‐mechano afferents innervating the skin in FM‐IgG treated animals fired significantly more action potentials after, but not during, mechanical force steps compared to healthy control‐IgG treated afferents. This sustained mechanically evoked activity mirrors the nociceptor hyperexcitability observed in people with FM, suggesting that autoreactive IgG might underly this phenomenon in patients. This adds to the growing body of evidence demonstrating that FM symptoms arise from changes in the peripheral nervous system generated by circulating autoreactive IgG.\n\n\n\n\n\n\n\n\n\nKey points\n\nPassive transfer of fibromyalgia (FM)‐IgG causes sensitization of mechano‐sensitive afferents in the skin of mice.\nAδ‐mechano and C‐mechano sensitive afferents in skin from mice injected with FM‐IgG display more after‐discharge following mechanical stimulation than mice injected with healthy control‐IgG.\nChanges in the peripheral nervous system caused by circulating autoreactive IgG play a role in FM signs and symptoms.\n\n\n"]