Microglial TRPV2-mediated neuroinflammation promotes central sensitization through microglial polarization in a vestibular migraine mouse model.

BackgroundNeuroinflammation, which is mediated by microglial activation, contributes to central sensitization, a key mechanism in vestibular migraine (VM). Transient receptor potential vanilloid 2 (TRPV2)-mediated calcium influx enhances nucleotide-binding oligomerization domain; leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome assembly, potentially driving inflammation. This study investigated the role of TRPV2 in VM pathogenesis.MethodsA VM model was established via repeated intraperitoneal injections of nitroglycerin and kainic acid-induced vestibular nerve terminal impairment. Periorbital thresholds and vestibular scores were measured to assess allodynia and vestibular dysfunction. Western blotting and immunofluorescence were used to evaluate TRPV2, ionized calcium-binding adapter molecule 1 (IBA1), interleukin-1β and NLRP3 expression in the spinal trigeminal nucleus caudalis (Sp5c) region. In vitro, BV2 cells treated with lipopolysaccharide and interferon-γ were transfected with TRPV2 small interfering RNA. TRPV2 activity was analyzed via patch-clamp electrophysiology. Microglial polarization and morphology were examined via flow cytometry and immunofluorescence, with a focus on CD16, CD63, CD206 and CD163 markers. NLRP3 inflammasome activation was assessed through western blotting and immunofluorescence.ResultsVM-related behaviors, including allodynia and dizziness, were successfully reproduced. Central sensitization in the Sp5c was marked by increased TRPV2 expression in microglia, as demonstrated by co-localization with the microglial marker IBA1. In vitro, TRPV2 inhibition in BV2 cells shifted microglial polarization from the pro-inflammatory M1 state to the anti-inflammatory M2 state. Additionally, TRPV2 blockade significantly reduced NLRP3 inflammasome activation and the levels of proinflammatory cytokines.ConclusionsTRPV2 regulates microglial activation and NLRP3 inflammasome activity via polarization mechanisms, contributing to central sensitization in VM. These findings highlight the critical role of TRPV2 in VM pathogenesis and its potential as a therapeutic target.