Figure 1

Hypothesized model of nociceptive pathways in migraine pathophysiology. Cortical spreading depression (CSD) is associated with the release of neurotransmitters and metabolites, which are thought to be the underlying cause of the migraine aura. These neurotransmitters may also activate perivascular trigeminal nerve endings, resulting in activation of the trigeminovascular system (TGVS), and subsequently, the trigeminal nucleus caudalis (TNC), which conveys signals to the thalamus en route to the somatosensory cortex. In addition, activation of the TGVS induces meningeal neurogenic inflammation, which could result in the central sensitization.