In conclusion, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via reducing the phosphorylation degree of p38, JNK or ERK, and inhibiting the activation of histone acetylation, finally it could reach the goal of recovering normal nerve histological forms and relieving pains of TN. Here, TRPV4 is linked to trigeminal nerve disorder.