Short-term environmental exposures and trigeminal neuralgia-related hospital admissions: a time-stratified case-crossover study with exploratory bioinformatic analysis of SO2-related pathways

Environmental exposures may be associated with trigeminal neuralgia (TN), but evidence regarding the roles of air pollution and meteorological factors remains limited, and the potential biological pathways are not well understood. Identifying environmental factors associated with TN may improve understanding of disease exacerbation patterns and provide insights that could complement existing pharmacological and surgical management strategies. We conducted a time-stratified case-crossover study among patients with TN-related hospital admissions. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (95% CI) for short-term associations of air pollutants and meteorological factors with TN-related hospital admission across single-day lag and moving-average exposure windows. Effect modification was examined according to greenness (Normalized Difference Vegetation Index, NDVI), nighttime light, and the roadside noise barrier–related spatial indicator. False discovery rate (FDR) correction was applied for multiple testing. For the pollutant showing the strongest and most consistent association across the primary and sensitivity analyses, exploratory and hypothesis-generating bioinformatic analyses integrated pollutant- and TN-related genes from public databases, followed by protein–protein interaction and functional enrichment analyses. Among 3,602 patients with TN-related admissions, short-term sulfur dioxide (SO 2 ) and ozone (O 3 ) exposures were associated with higher odds of admission. SO 2 showed the most consistent association: each increase at 7 days before admission (lag 7) was associated with higher odds of admission (OR = 1.06, 95% CI: 1.02–1.11; FDR-adjusted P = 0.03), with similar results after co-pollutant adjustment. O 3 was positively associated with TN-related hospital admission over the admission day and preceding 21 days (ma21), with an OR of 1.77 (95% CI: 1.35–2.31) for the highest versus lowest tertile (FDR P for trend < 001). Higher wind speed was positively associated with higher odds of admission, although these associations did not remain significant after FDR correction. The association between temperature and TN-related hospital admission differed across levels of monthly NDVI, suggesting potential effect modification by greenness. Exploratory bioinformatic analysis of SO 2 identified six genes shared with TN (CXCL8, IL6, MMP9, PTGS2, TLR2, and TNF), with enrichment in inflammatory, oxidative stress, hypoxia, IL-17, TNF, and Toll-like receptor pathways. These findings were considered hypothesis-generating rather than mechanistic evidence. Short-term exposure to SO 2 and O 3 were associated with higher odds of TN-related hospital admission. Greenness may modify the association between temperature and TN-related hospital admission. The exploratory bioinformatic findings generated candidate hypotheses involving inflammatory, immune, and oxidative stress pathways but did not confirm biological mechanisms underlying the SO 2 –TN association.