J Neurochem. 2026 Nov;170(11):e70573. doi: 10.1111/jnc.70573.
ABSTRACT
Central post-stroke pain (CPSP) is a chronic neuropathic pain condition associated with thalamic injury and frequently accompanied by affective disturbances. Although SGK1 has been implicated in neuroinflammation and behavioral regulation, its role and underlying mechanisms in CPSP remain unclear. In this study, a thalamic hemorrhage mouse model was established by collagenase injection to investigate the contribution of SGK1 to CPSP-like phenotypes. Behavioral assessments were performed to evaluate pain hypersensitivity, cold allodynia, and anxiety-like behaviors. Pharmacological inhibition and viral-mediated overexpression of SGK1 were used to examine its effects on pathological injury, inflammatory responses, and the GSK-3β/β-catenin signaling pathway. Thalamic hemorrhage induced persistent mechanical allodynia, cold hypersensitivity, and anxiety-like behaviors. SGK1 expression was upregulated in microglia and astrocytes, peaked at day 7, and remained elevated until day 28 after hemorrhage. SGK1 inhibition alleviated pain-related behaviors, pathological damage, and neuroinflammation, whereas SGK1 overexpression produced opposite effects. Mechanistically, SGK1 modulation was associated with changes in GSK-3β Ser9 phosphorylation, β-catenin accumulation, and inflammatory cytokine expression. These findings identify SGK1 as a critical regulator of CPSP progression and suggest that targeting the SGK1/GSK-3β/β-catenin signaling axis may represent a potential therapeutic strategy for post-stroke pain.
PMID:42952032 | DOI:10.1111/jnc.70573