The P2x4r-Bdnf Pathway In Microglia Mediates Pulpitis-Induced Pain

The analgesia effect of pulpitis is not satisfaction, we Investigating the central mechanisms of pulpitis pain to provide a basis for analgesic targets in pulpitis. Adult male C57 mice (20-26g) were used to establish experimental pulpitis models by exposing the pulp of the left maxillary first molar. Mechanical allodynia was evaluated using vonFrey filaments. Immunofluorescence staining and Western blotting were performed to examine neuronal and brain-derived neurotrophic factor (BDNF) in the insular cortex (IC). Stereotaxic intracerebral cannulation combined with behavioral testing assessed BDNF's effects on pain.In vivo electrophysiology was used to record the field potential changes and neuronal firing patterns in the IC, comparing baseline and BDNF-treated conditions between control and pulpitis groups. We cultured microglia in vitro and stimulated with LPS, ATP and 5-BDBD. The production and release of BDNF will be measured using Western blot and ELISA techniques. (Ethics approval number: 2023JCZD56) Following pulp exposure, mice exhibited decreased pain thresholds with progressive dental inflammation, accompanied by increased Fos and BDNF/TrkB expression in the IC, while local IC drug administration further significantly reduced pain thresholds in pulpitis mice.In vivo electrophysiological recordings demonstrated that BDNF primarily promotes pulpitis pain by increasing theta oscillation and the firing rate of pyramidal (PYR) neurons in the IC. Microglia participate in pulpitis pain by regulating BDNF secretion through P2X4 receptors.(P<0.05) In the IC, microglia regulate BDNF release via P2X4 receptors, and this BDNF promotes neuronal hyperexcitability to exacerbate nociception in pulpitis model mice.