Microglial Responses and Pain Behaviors Are Exacerbated by Chronic Sleep Deprivation in Rats with Chronic Pain Via Neuroinflammatory Pathways

inflammatory response of central nervous system (CNS) and microglial activation is important in the development of pain behaviors induced by sleep deprivation. We found that chronic sleep deprivation (CSD) aggravated pain behaviors in rats with chronic pain by upregulating expression of Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3), and interleukin 1b (IL-1b), which promoted micro-glial activation in the brain. We also found that CSD increased numbers of Iba1+ and TLR4+ cells, as well as neu-ronal apoptosis. Inhibitors of TLR4 and NLRP3 (TAK-242 and MCC950, respectively) reduced expression levels of inflammatory factor proteins and M1-related factor mRNA, decreased microglial activation, and relieved the hyper-algesia caused by CSD. These results suggest that CSD aggravated pain behavior in rats with chronic pain through the TLR4/NLRP3/IL-1b signaling pathway, which mediates microglial activation and promotes CNS inflammation and neuronal apoptosis.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study found that chronic sleep deprivation aggravated pain behaviors in rats with chronic pain by upregulating the expression of TLR4, NLRP3, and IL-1β, which promoted microglial activation. CSD also increased neuronal apoptosis and CNS inflammation. Inhibitors of TLR4 and NLRP3 reduced inflammatory factor proteins, relieved microglial activation, and alleviated hyperalgesia caused by CSD. The TLR4/NLRP3/IL-1β signaling pathway mediates the exacerbation of pain behaviors in rats with chronic pain induced by CSD.