Mediation Effect of CSF Substance P on the Association Between Smoking and Sleep.

Background: Cigarette smoking has been linked to severe and persistent sleep disturbances alongside notable fluctuations in neuropeptide levels. Substance P (SubP), influenced by smoking, also impacts sleep-wake cycles. However, its specific role in smoking-induced sleep disorders remains unclear. This study aimed to explore the connection between cigarette smoking and sleep quality by examining SubP levels in cerebrospinal fluid (CSF) and identifying potential treatment avenues for sleep disorders.

Methods: A total of 146 Chinese men (93 nonsmokers, 53 active smokers) undergoing lumbar puncture before anterior cruciate ligament reconstruction were enrolled. Clinical data and Pittsburgh Sleep Quality Index (PSQI) scores were assessed, followed by CSF sample collection and CSF SubP level measurement.

Results: Active smokers exhibited significantly higher PSQI scores (4.02 ± 2.27 vs. 2.60 ± 2.46, p < 0.001) and CSF SubP levels (2111 ± 212 vs. 1821 ± 289, p < 0.001) compared to nonsmokers. A negative correlation (r = -0.434, p < 0.001) between SubP levels and PSQI scores was observed in all participants and nonsmokers, while no correlation (r = -0.044, p = 0.72) was found in active smokers. Logistic regression analysis across different dimensions of sleep disorders indicated associations between CSF SubP levels and sleep quality as well as daytime dysfunction (OR = 0.439 (0.211-0.891), p = 0.025; OR = 0.308 (0.152-0.608), p = 0.001). Mediation analysis suggested that CSF SubP levels mediated the relationship between smoking and sleep.

Conclusion: CSF SubP levels are elevated in active smokers and appear to play a mediating role in the relationship between smoking and sleep regulation, as evidenced by a negative correlation between CSF SubP levels and PSQI scores.