Potential modulation of pain perception in animal models of acute sleep deprivation: implications of different stress response mechanisms

J Headache Pain. 2026 Apr 28. doi: 10.1186/s10194-026-02371-6. Online ahead of print.

Sleep deprivation is a common phenomenon in modern society and can influence pain perception. However, inconsistencies have emerged in mechanistic studies investigating this relationship. We hypothesize that these discrepancies may stem from the use of different animal models of sleep deprivation. Therefore, we evaluated the effects of three commonly used and one newly improved sleep deprivation paradigms on pain responses and explored the underlying mechanisms contributing to their different effects. Our findings revealed that distinct sleep deprivation paradigms exert varying effects on pain sensitivity in mice, with corresponding differences in the stress responses elicited by each model. Among the four acute 6-hour sleep deprivation paradigms tested, multiple platform-induced sleep deprivation induced the most pronounced stress response. The activation levels of locus coeruleus noradrenergic neurons were identified as a biomarker reflecting the effect of sleep deprivation on stress in mice. Consequently, research examining the comorbidity of acute sleep deprivation and pain should carefully consider the differences between different sleep deprivation models and employ appropriate experimental designs to minimize potential biases.

PMID:42050411 | DOI:10.1186/s10194-026-02371-6