VX-765 Attenuates Central Post-Stroke Pain by Inhibiting Pyroptosis

doi:10.3870/j.issn.1672-0741.26.01.007

Abstract

Abstract: Objective To investigate whether pyroptosis occurs in central post-stroke pain(CPSP)and whether modulation of the NLRP3/GSDMD/IL-1β pathway can alleviate central sensitization. Methods A CPSP model was established by distal middle cerebral artery occlusion via electrocoagulation(dMCAO).C57BL/6J mice were randomly assigned to four groups:Sham+Vehicle,Sham+VX-765,CPSP+Vehicle,and CPSP+VX-765.Protein levels of NLRP3,GSDMD-N,Caspase-1,and IL-1β were measured by Western blotting.Neuronal survival was assessed via Nissl staining.Mechanical and thermal withdrawal threshold of bilateral hind paws were evaluated using von Frey filaments and the Hargreaves test,respectively. Results On day 14 post-modeling,compared with the Sham+Vehicle group,the CPSP+Vehicle group exhibited significantly increased expression of NLRP3,GSDMD-N,Caspase-1 and IL-1β.Neurons around the infarct area showed dissolution and loss of Nissl bodies,along with reduced cell survival.Both mechanical and thermal withdrawal thresholds were significantly decreased.Following VX-765 intervention,the CPSP+VX-765 group displayed decreased expression level of pyroptosis-related proteins,increased neuronal survival around the infarct,and improved withdrawal thresholds. Conclusion VX-765 exerts neuroprotective effects and alleviates central sensitization in CPSP by inhibiting the NLRP3/GSDMD/IL-1β pathway.

Key words: central post-stroke pain, hyperalgesia, inflammation, pyroptosis, Caspase inhibitor

CLC Number:

R743.3

Liu Qianwen, Ye Yingze, She Kepeng et al. VX-765 Attenuates Central Post-Stroke Pain by Inhibiting Pyroptosis[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(2): 149-154.

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