Causal relationship between immunocytes and circulating cytokines in post-herpetic neuralgia: a Mendelian randomization study

Post-herpetic neuralgia (PHN) poses a significant challenge in pain management following herpes zoster infection, involving both the central and peripheral immune system. Inflammatory cells and mediators induce local inflammation, enhance neuronal excitability, and alter pain transmission pathways. Different immune cells contribute variably to PHN, with some immune cells exhibiting dual roles. An understanding of the roles of different immune cells and inflammatory factors in PHN is therefore important and may aid in identifying new immunotherapeutic approaches. To investigate the effects of diverse cytokines and immune cell phenotypes on PHN. Materials & Methods: We conducted Mendelian randomization (MR) analysis utilizing publicly available genome-wide association study data. Instrumental variable selection adhered to stringent criteria to ensure robustness. We employed various analytical methods, including the Inverse Variance Weighted method, sensitivity analyses, and reverse MR, to assess causal relationships. Our study identified causal relationships between PHN and various cytokines and immune phenotypes using two-sample MR analysis. One cytokine and five immune phenotypes were shown to reduce the risk of PHN, notably CD8dim T cell absolute count (OR: 0.483, 95% CI: 0.239-0.976, p=0.043). Conversely, one cytokine and one immune phenotype were shown to increase the risk of PHN. SNP selection indicated robust instrumental variables, and sensitivity analyses confirmed no significant heterogeneity or horizontal pleiotropy. Reverse MR revealed no causal effect of PHN on these factors, suggesting a unidirectional relationship. Our study provides insights into the role of immune factors in PHN, revealing potential targets for therapeutic interventions. Further research is warranted to validate these findings and explore personalized treatment strategies for PHN management.