Systemic inflammatory regulators are associated with two common types of neuropathic pain: A bidirectional Mendelian randomization study.

Background: Currently, there is limited and inconsistent evidence regarding the causal relationship between systemic inflammatory regulators and two common types of neuropathic pain, namely, postherpetic neuralgia (PHN) and trigeminal neuralgia (TN). This study employed a Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory regulators and these two common neuropathic pain conditions.

Methods: In this study, 41 single-nucleotide polymorphisms (SNPs) associated with PHN and TN were selected as instrumental variables (IVs) representing systemic inflammatory regulators. Genetic associations of systemic inflammatory regulators were derived from recent genome-wide association studies (GWAS) on the human proteome and cytokines. Genetic data related to PHN and TN were obtained from the FinnGen. The primary analytical method utilized inverse variance weighting (IVW) and various sensitivity analyses.

Results: Prior to applying the false discovery rate (FDR) correction, our bidirectional MR analysis revealed that increased levels of IFNγ (OR: 0.46, 95% CI: 0.24-0.87, P: 0.016) and MCP3 (OR: 0.52, 95% CI: 0.35-0.77, P: 0.001) were associated with a reduced risk of PHN, and increased levels of IL-16 (OR: 0.81, 95% CI: 0.67-0.98, P: 0.026) were causally associated with a reduced risk of TN. In discussing the impact of PHN and TN on systemic inflammatory regulator levels, we observed the following findings: The BETA for CTACK was -0.07 (95% CI: -0.13 to -0.01, P: 0.015), the BETA for FGFBasic was -0.04 (95% CI: -0.08 to -0.01, P: 0.020), and the BETA for IL-17 was -0.04 (95% CI: -0.08 to -0.01, P: 0.019). These results indicate that patients with PHN tend to have lower levels of CTACK, FGFBasic, and IL-17. Conversely, the BETA for IFNγ was -0.09 (95% CI: -0.18 to 0.00, P: 0.046), suggesting that patients with TN tend to have lower levels of IFN γ. However, after FDR correction, only the association between MCP3 and PHN remained statistically significant (P: 0.044).

Conclusion: This study found that certain systemic inflammatory regulators are associated with PHN and TN to some extent. However, further research is needed to explore the specific mechanisms underlying these connections.