Lai Shenglong, Li Haiyang, Xing Yazhou, Wu Du, Wang Lin, Liang Qinghua
Department of Neurosurgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, 450003, China.
Brain Behav Immun Health. 2024 Dec 27;43:100930. doi: 10.1016/j.bbih.2024.100930. eCollection 2025 Feb.
Trigeminal neuralgia (TN) is a severe facial pain disorder with complex etiology. Inflammation has been suggested as a contributing factor to TN pathogenesis. This study investigates the causal relationship between inflammatory biomarkers, including 41 circulating inflammatory cytokines, C-reactive protein (CRP), and procalcitonin (PCT), and TN using Mendelian randomization (MR) analysis.
A two-sample MR approach was employed using genome-wide association study (GWAS) data from 8293 Finnish individuals for inflammatory cytokines and data from the FinnGen database for TN. Instrumental variables (IVs) were selected based on genome-wide significance and clumping thresholds to avoid linkage disequilibrium. Inverse variance weighting (IVW) was used as the primary method, complemented by MR Egger regression, weighted median, simple mode, and weighted mode methods. Additionally, Bayesian Weighted MR (BWMR) and Multivariable MR (MVMR) were utilized to validate the findings and explore potential confounders.
The present MR analysis identified significant causal associations for three inflammatory cytokines with TN. Stem cell growth factor beta (SCGF-β) (OR = 1.362, 95% CI = 1.049-1.770, p = 0.021) and Interleukin-4 (IL-4) (OR = 1.533, 95% CI = 1.014-2.316, p = 0.043) were positively associated with TN, while Interleukin-16 (IL-16) (OR = 0.720, 95% CI = 0.563-0.921, p = 0.009) had a protective effect. CRP levels were also linked to TN risk (OR = 0.751, 95% CI = 0.593-0.951, p = 0.017). No significant causal effect of PCT on TN was observed. Sensitivity analyses confirmed the robustness of these findings, showing no evidence of horizontal pleiotropy or heterogeneity.
This study highlights specific inflammatory biomarkers that may play pivotal roles in TN pathogenesis. SCGF-β and IL-4 are potential therapeutic targets due to their facilitative effects on TN, while IL-16 could offer protective benefits. CRP's association with TN further supports the involvement of systemic inflammation in this condition. These findings provide novel insights into TN's inflammatory mechanisms, suggesting new avenues for targeted interventions.
三叉神经痛（TN）是一种病因复杂的严重面部疼痛疾病。炎症被认为是TN发病机制的一个促成因素。本研究使用孟德尔随机化（MR）分析来探究炎症生物标志物与TN之间的因果关系，这些生物标志物包括41种循环炎症细胞因子、C反应蛋白（CRP）和降钙素原（PCT）。
采用两样本MR方法，使用来自8293名芬兰个体的全基因组关联研究（GWAS）数据作为炎症细胞因子的数据，并使用FinnGen数据库中TN的数据。基于全基因组显著性和聚类阈值选择工具变量（IV）以避免连锁不平衡。采用逆方差加权（IVW）作为主要方法，并辅以MR Egger回归、加权中位数、简单模式和加权模式方法。此外，利用贝叶斯加权MR（BWMR）和多变量MR（MVMR）来验证研究结果并探索潜在的混杂因素。
目前的MR分析确定了三种炎症细胞因子与TN之间存在显著的因果关联。干细胞生长因子β（SCGF-β）（OR = 1.362，95%CI = 1.049 - 1.770，p = 0.021）和白细胞介素-4（IL-4）（OR = 1.533，95%CI = 1.014 - 2.316，p = 0.043）与TN呈正相关，而白细胞介素-16（IL-16）（OR = 0.720，95%CI = 0.563 - 0.921，p = 0.009）具有保护作用。CRP水平也与TN风险相关（OR = 0.751，95%CI = 0.593 - 0.951，p = 0.017）。未观察到PCT对TN有显著的因果效应。敏感性分析证实了这些结果的稳健性，未显示出水平多效性或异质性的证据。
本研究突出了特定的炎症生物标志物可能在TN发病机制中起关键作用。SCGF-β和IL-4因其对TN的促进作用而成为潜在的治疗靶点，而IL-16可能具有保护作用。CRP与TN的关联进一步支持了全身炎症在这种疾病中的参与。这些发现为TN的炎症机制提供了新的见解，为靶向干预提出了新的途径。
