Ligustrazine alleviates spinal cord injury-induced neuropathic pain by inhibiting the TLR4/NF-κB signaling pathway

To investigate the effects of ligustrazine on neuropathic pain (NPP) in rats with sciatic nerve injury and to provide new scientific insight for broadening the clinical application of ligustrazine. Human spinal cord cell line STR cells were transfected with TLR4-mimic or mimic negative control (mimic-NC). After transfection, the STR cells were treated with different concentrations of ligustrazine (0, 0.25, 0.5, 1, 2 μm) for 24 h or 48 h. Cell proliferation was detected by MTT assay and colony formation assay. A rat model was further constructed to evaluate mechanical and cold pain sensitivity behaviors by fiber mechanical stimulation and freezing spray. The extracellular fluids of medial prefrontal cortex (mPFC) and central amygdala (CeA) were collected by intracranial dual-site simultaneous microdialysis. The contents of glutamic acid (Glu), aspartate (Asp), glycine (Gly), and γ-aminobutyric acid (GABA) in extracellular fluids were detected by HPLC. Compared to the 0 μm group, ligustrazine concentration at 0.5 μm significantly decreased the relative cell viability of STR cells and promoted the cell apoptosis rate. Ligustrazine at 0.25 μm significantly reduced the colony number of STR cells (all P