Immune profiling in trigeminal neuralgia reveals altered cytokine and chemokine signatures in cerebrospinal fluid and serum

Introduction Trigeminal neuralgia (TN) is a debilitating neuropathic pain disorder traditionally attributed to neurovascular compression; however, this mechanism does not fully explain the marked clinical heterogeneity or persistent pain observed in a subset of patients. Increasing evidence suggests that central neuroinflammatory processes contribute to neuropathic pain, but immune profiles in the cerebrospinal fluid (CSF) and serum of patients with TN remain poorly characterized. Methods We conducted a single-center cross-sectional study including 14 patients with TN and 19 non-pain controls. CSF samples were obtained from 14 TN patients and 10 controls, while serum samples were available from 10 TN patients and 9 controls. Concentrations of a broad panel of cytokines, chemokines, and growth factors were measured using multiplex immunoassays. Group comparisons were performed using non-parametric statistical tests, with false discovery rate correction for multiple comparisons. Results Patients with TN reported severe pain (median numerical rating scale score: 8), whereas controls reported no pain. Demographic characteristics, including age, sex, and body mass index, were comparable between groups. Compared with controls, CSF from TN patients showed significantly elevated levels of multiple pro-inflammatory cytokines and chemokines, including TNF-α TNF-β, IL-1β, IL-9, IL-16, IL-17, IL-18, IFN-γ, CCL5, CXCL12, and macrophage migration inhibitory factor (MIF) (all false discovery rate-adjusted p 0.05). In contrast, vascular endothelial growth factor (VEGF) concentrations were significantly reduced in the CSF of TN patients. No corresponding inflammatory alterations were observed in serum samples. Discussion TN is associated with a distinct CSF immune signature characterized by elevated pro-inflammatory mediators and altered growth factor profiles. These findings support the involvement of central neuroimmune mechanisms in the pathophysiology of TN and highlight the potential value of CSF biomarkers for improving mechanistic understanding and identifying novel therapeutic targets.