Sleep deprivation modulates pain sensitivity through alterations in lncRNA and mRNA expression in the nucleus accumbens and ventral midbrain

Abstract

Sleep deprivation (SD) is a growing public health concern with implications for pain sensitivity and well-being. Although the relationship between sleep and pain is well understood, the underlying mechanisms remain largely unknown. This study investigates how SD influences pain sensitivity by modulating gene expression in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of mice. Using the CPW sleep deprivation model, mice were deprived of sleep for three days, simulating preoperative conditions. Behavioral tests revealed heightened mechanical and thermal hypersensitivity post-SD. Brain MRI, immunofluorescence, and RNA sequencing analyses showed significant changes in the expression of non-coding RNAs (ncRNAs) and mRNAs in NAc and VTA, implicating several pain-related genes. Functional enrichment analysis highlighted pathways associated with neurotransmission, inflammation, and stress response. The study identified Hcrt and Apoe as critical modulators of SD-induced hyperalgesia, with potential therapeutic implications for managing pain associated with SD. Findings suggest that overlapping pathways exist between sleep and pain sensitivity, offering insights into the molecular mechanisms that connect sleep disorders with heightened pain responses.