Acute sleep deprivation induces hyperalgesia through P2X4-mediated microglial activation in mice

Perioperative insomnia is a common clinical phenomenon that is associated with increased pain sensitivity during the perioperative period. Understanding the mechanisms underlying acute sleep deprivation-induced hyperalgesia is crucial for improving pain management in these patients. The P2X4 receptor is a key modulator of pain, yet its role in hyperalgesia following acute sleep deprivation remains unclear. In this study, we established an acute sleep deprivation model in mice and found that sleep-deprived animals exhibited significant hyperalgesia along with marked microglial activation and elevated levels of proinflammatory cytokines in the hippocampal CA1 region. Notably, intracerebroventricular administration of the selective P2X4 receptor antagonist 5-BDBD during sleep deprivation significantly ameliorated hyperalgesia, inhibited microglial activation, and reduced cytokine levels. These results suggest that acute sleep deprivation activates P2X4 receptors, which in turn trigger microglial activation and inflammatory cytokine release, ultimately leading to hyperalgesia.