Mechanical sensitization of sensory afferents after passive transfer of fibromyalgia IgG

Fibromyalgia (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. KEY POINTS: Passive transfer of fibromyalgia (FM)-IgG causes sensitization of mechano-sensitive afferents in the skin of mice. Aδ-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. Changes in the peripheral nervous system caused by circulating autoreactive IgG play a role in FM signs and symptoms.