Mol Pain. 2026 Jan-Dec;22:17448069261484390. doi: 10.1177/17448069261484390. Epub 2026 Aug 26.
ABSTRACT
Central post-stroke pain (CPSP) remains difficult to treat due to limited understanding of its underlying mechanisms. Emerging evidence implicates microglia-driven neuroinflammation in CPSP development. Mitogen-activated protein kinase phosphatase-1 (MKP-1) negatively regulates MAPK signaling and modulates inflammation in neurological disorders, yet its role in CPSP is unclear. Using a mouse model of thalamic hemorrhage, we examined MKP-1 expression and function in CPSP. Behavioral testing assessed pain hypersensitivity and affective disturbances. Immunofluorescence and western blot evaluated MKP-1 expression, microglial activation, and inflammatory signaling in the thalamus. Pharmacological MKP-1 inhibition was employed to assess functional contributions. Thalamic hemorrhage induced persistent mechanical hypersensitivity and anxiety-like behaviors, accompanied by pronounced microglial activation in the peri-lesional thalamus. MKP-1 expression increased significantly after stroke and localized primarily to microglia. MKP-1 inhibition exacerbated pain behaviors and enhanced microglial activation, with corresponding increases in pro-inflammatory mediators and p38 MAPK phosphorylation. These findings suggest that MKP-1 may function as an endogenous negative regulator of microglia-mediated neuroinflammation following thalamic hemorrhage. Pharmacological modulation of MKP-1 signaling warrants further investigation as a potential approach for CPSP.
PMID:42647815 | DOI:10.1177/17448069261484390