International Journal of Molecular Sciences · 9 authors, 5 centres
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This preclinical mouse study found that chronic restraint stress caused mechanical hyperalgesia in wild-type mice, which was significantly reduced in female but not male IL-1 knockout mice. This suggests IL-1 mediates stress-induced pain specifically in females.
The study investigated the role of interleukin-1 (IL-1) in a chronic restraint stress (CRS) mouse model of hyperalgesia. Female and male WT and IL-1 KO mice were subjected to 6 hours of daily immobilization for 4 weeks. CRS induced mechanical hyperalgesia in both sexes of WT mice after 2 weeks, which was significantly attenuated in female but not male IL-1 KO mice. Histological analysis revealed increased IBA1+ microglia integrated density in pain-related brain regions of stressed WT mice, which was absent in KO mice, along with stress-induced morphological changes in GFAP+ astrocytes in WT but not KO mice. Anxiety and depression-like behaviors and endocrine changes were observed after 2 weeks but not after 4 weeks, indicating adaptation. The findings demonstrate that IL-1 mediates chronic stress-induced hyperalgesia in female mice, linked to microglia and astrocyte changes, highlighting sex differences in stress-related pain mechanisms.
