Reducing IgG accumulation via neonatal Fc receptor (FcRn) blockade relieves neuropathic pain.

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Tác giả: Dorsa Dayani, Nathan T Fiore, Peter M Grace, Cobi J Heijnen, Kendal F Willcox, Younus A Zuberi

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : Brain, behavior, and immunity , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 701556

Preclinical and clinical studies have established that autoreactive immunoglobulin G (IgG) can drive neuropathic pain. We recently demonstrated that sciatic nerve chronic constriction injury (CCI) in male and female mice results in the production of pronociceptive IgG, which accumulates around the lumbar region, including within the dorsal root ganglia (DRG) and spinal cord, facilitating the development of neuropathic pain. These data raise the intriguing possibility that neuropathic pain may be alleviated by reducing the accumulation of IgG. To this end, we tested whether biologic inhibition or genetic deletion of the neonatal Fc receptor (FcRn) would attenuate mechanical hypersensitivity (allodynia) and IgG deposition induced by CCI. FcRn are prominently expressed on myeloid and endothelial cells and extend the half-life of IgG via pinocytosis and recycling into the extracellular milieu. We show here that administration of the FcRn blocker efgartigimod either 7- or 28-days post-CCI relieved allodynia among both male and female mice, compared to the Fc fragment control. Efgartigimod, administered systemically (intraperitoneal) or to the lumbar region (intrathecal), attenuated mechanical allodynia for at least one month. CCI-induced allodynia was similarly reduced in FcRn-deficient (FcRn
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