Causal Relationship Between Circulating Inflammatory Cytokines and the Risk of Trigeminal Neuralgia: A Mendelian Randomization Study.

Background: Inflammatory regulators play a fundamental role in the development of trigeminal neuralgia (TN). However, the precise mechanisms and causal relationship with the risk of TN remain poorly understood.

Methods: This study aimed to assess the causal relationship between 41 inflammatory cytokines and TN using Mendelian randomization (MR) analysis. A two-sample MR approach was utilized, employing genetic variation data on TN from a large publicly available genome-wide association study (GWAS) comprising 1777 cases of European ancestry and 360,538 controls. Additionally, summary data from a GWAS on inflammatory cytokines, comprising 8293 healthy participants, were utilized. The causal relationship between exposure and outcome was primarily assessed using the inverse variance weighted (IVW) method, accompanied by sensitivity analyses.

Results: The study revealed an association between increased risk of TN and cutaneous T cell-attracting chemokine（CTACK） (odds ratio [OR] = 1.187; 95% confidence interval [CI], 1.041-1.35; p = 0.01) and interferon (IFN)-gamma（MIG） (OR = 1.232; 95% CI, 1.080-1.449; p = 0.01), while interleukin (IL)-16 (OR = 0.823; 95% CI, 0.685-0.989; p = 0.03) and interferon (IFN)-G (OR = 0.779; 95% CI, 0.612-0.992; p = 0.04) were associated with decreased risk of TN. Notably, no potential effect of TN on inflammatory factors was observed.

Conclusion: This study provides novel insights into the pathogenesis of TN, highlighting the crucial role of inflammatory cytokines in TN risk.

Significance: This study advances our understanding of TN by using MR to identify the causal roles of specific inflammatory cytokines. These results underscore the importance of inflammation in TN development and suggest potential targets for new treatments.