Association of Baseline Systemic Immune-Inflammation Index With Severe Sleep Disturbance in Patients With Neuropathic Pain: A Prospective Longitudinal Observational Cohort Study.

BACKGROUND: Patients with neuropathic pain frequently experience impaired sleep quality. The systemic immune-inflammation index (SII) is a readily available blood-based inflammatory marker, but its association with sleep disturbance in neuropathic pain patients remains insufficiently defined. METHODS: This single-center prospective longitudinal observational cohort study enrolled 135 patients aged 40-65 years with neuropathic pain confirmed by the DN4 questionnaire, disease duration of 6-12 months, and pain inadequately controlled by conventional medication. Baseline severe sleep disturbance was defined using a prespecified severity-based threshold of PSQI > 10. Fasting blood and first-morning spot urine samples were collected at baseline and at the 1-month follow-up after PRF. SII was calculated as platelet count x neutrophil count/lymphocyte count. Native urinary melatonin concentration was measured by ELISA and reported as an unadjusted spot urine concentration. The primary analysis evaluated the association between baseline SII and severe sleep-disturbance status; post-PRF changes were interpreted as within-subject temporal changes because no control group was included. RESULTS: At baseline, 73 of 135 patients met the prespecified criterion for severe sleep disturbance. Compared to the nonsevere group, the severe group had higher baseline SII (803.03 ± 111.45 vs. 604.21 ± 164.29, p < 0.001) and lower urinary melatonin concentration (8.32 ± 2.17 vs. 9.61 ± 2.72, p = 0.006). At the 1-month follow-up, severe sleep-disturbance status was present in 9 patients (McNemar test, p < 0.001). SII decreased, and urinary melatonin concentration increased in both baseline severity groups (all within-group p < 0.001). In a limited multivariable logistic regression model adjusted for available baseline covariates, baseline SII was associated with severe sleep-disturbance status (adjusted OR per 1-unit increase: 1.011; 95% CI: 1.007-1.014; p < 0.001). Exploratory ROC analysis yielded an apparent in-sample AUC of 0.833. CONCLUSIONS: Higher baseline SII was associated with severe sleep-disturbance status in this mixed neuropathic pain cohort. The observed longitudinal changes after PRF should be interpreted cautiously as within-subject temporal changes rather than PRF-specific effects. The findings are exploratory and do not establish causality, a direct inflammatory mechanism, or validated predictive performance. TRIAL REGISTRATION: Chinese Registry of Clinical Trials: ChiCTR2500103587.