Neuroimmune related pathway may involve in neuropathic pain after brachial plexus injury: a clinical and experimental discovery.

To find the pathways of neuropathic pain after brachial plexus avulsion injury, we screen out key molecules or related signal pathways. Serum samples were collected from 20 patients with brachial plexus injury (BPI) and 10 healthy controls. A BPI rat model was constructed, divided into control, sham, and operated groups. Subtype injuries (upper, lower, complete avulsion) were further modeled. Protein profiles were analyzed using Raybiotech GSH-INF-3 and AAH-NEU-2 antibody microarrays. In clinical samples, 5 cytokines (MMP-3, CNTF, GM-CSF, IL-18, TGF-β) were differentially expressed between BPI patients and healthy controls, among which IL-18, CRP, and GM-CSF were elevated in the pain group compared to the painless group. In rats, serum cytokines showed no significant differences; however, nerve tissue analysis revealed increased levels of IL-6, IL-13, MCP-1, and TNF-α in the operated BPI group compared to the sham group. Histological and immunohistochemical analyses showed progressively severe nerve degeneration and inflammatory responses in upper, lower, and complete injury models. There were signal pathways related to autoimmune diseases screened out, such as IL-17 signaling pathway, inflammatory bowel disease, and Th1 and Th2 cell differentiation. This study suggests that cytokines may affect neuropathic pain in inflammatory pathway and neuroimmune pathway.