Fig. 1

Peripheral model of migraine initiation. Activated primary afferents innervating blood vessels of the dura transmit signals to the TCC, a relay center in the brainstem. The TCC also receives input from the cervical dorsal root ganglia of the C1-C3 nerves, which primarily innervate the back of the head and upper neck. Second-order neurons then relay signals from the brainstem to the thalamus, which projects them to various regions of the somatosensory cortex, where pain perception occurs. Effective medications with inability to cross BBB are believed to prevent the attack by inhibition of sensory nerves at the level of the meninges. BBB, blood-brain barrier; TCC, trigeminal cervical complex. C1-C3: cervical nerves. Created in https://BioRender.com