Additionally, EB could upregulate the expression of synaptic proteins (PSD95, SYN1, and BDNF) in the hippocampus.<h4>Conclusion</h4>EB alleviates neuroinflammation by reducing EGFR and PTGS2 protein expression, modulates synaptic plasticity, and improves pain-depression comorbidity. Here, EGFR is linked to major depressive disorder.