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.