Overall, the research work found to be the expression of PACAP and PAC1R in TNC was elevated after repeated treatment of NTG to rats. In addition, via modifying NTG-induced synaptic plasticity via the ERK/CREB/BDNF pathway, PACAP6-38, a selective PAC1R antagonist, reduced chronic cephalic allodynia and inhibited the augmentation of neuronal activity. Inhibiting PACAP/PAC1R could be a new therapeutic target for migraine based on our findings. The gene discussed is CREB1; the disease is migraine disorder.