This study has several highlights: 1) XZR, a Chinese herbal decoction, was effective in improving migraine-like behavior, including frequent head scratching, photophobia, and hyperalgesia; 2) XZR inhibited inflammation mediated by the NF-κB signaling pathway and the expression of CGRP in NTG-induced migraine; 3) XZR inhibited the NF-κB signaling pathway activation by inhibiting NOS in NTG-induced migraine; and 4) imperatorin and xanthotoxin interacted with nNOS and inhibited the NF-κB signaling pathway, suggesting that imperatorin and xanthotoxin might be effective substances in XZR. This evidence concerns the gene NFKB1 and Photophobia.