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Papers of the Week


Papers: 7 Dec 2019 - 13 Dec 2019


Animal Studies, Human Studies


2020 Apr


Pain


161


4

Complex regional pain syndrome patient IgM has pronociceptive effects in the skin and spinal cord of tibia fracture mice.

Authors

Guo T-Z, Wei T, Tajerian M, Clark DJ, Birklein F, Goebel A, Li W-W, Sahbaie P, Escolano FL, Herrnberger M, Kramer HH, Kingery WS
Pain. 2020 Apr; 161(4):797-809.
PMID: 31815913.

Abstract

It has been proposed that Complex Regional Pain Syndrome (CRPS) is a post-traumatic autoimmune disease. Previously we observed that B cells are required for the full expression of CRPS-like changes in a mouse tibia fracture model and that serum IgM antibodies from fracture mice have pronociceptive effects in muMT fracture mice lacking B cells. The current study evaluated the pronociceptive effects of injecting CRPS patient serum or antibodies into muMT fracture mice by measuring hindpaw allodynia and unweighting changes. CRPS serum binding was measured against autoantigens previously identified in the fracture mouse model. Both CRPS patient serum or IgM antibodies had pronociceptive effects in the fracture limb when injected systemically in muMT fracture mice, but normal subject serum and CRPS patient IgG antibodies had no effect. Furthermore, CRPS serum IgM antibodies had pronociceptive effects when injected into the fracture limb hindpaw skin or intrathecally in the muMT fracture mice. Early (1-12 months post injury) CRPS patient (n=20) sera were always pronociceptive after systemic injection and chronic (>12 months post injury) CRPS sera were rarely pronociceptive (2/20 patients), while sera from normal subjects (n=20) and from patients with uncomplicated recoveries from orthopedic surgery and/or fracture (n=15) were never pronociceptive. Increased CRPS serum IgM binding was observed for keratin 16, histone 3.2, gamma actin, and alpha enolase autoantigens. We postulate that CRPS patient IgM antibodies bind to neoantigens in the fracture mouse skin and spinal cord to initiate a regionally restricted pronociceptive complement response potentially contributing to the CRPS disease process.