Initially, this approach of targeting neuropeptides that were upregulated following experimental trigeminovascular activation and further based on a developing theory of migraine as a disorder of neurogenic inflammation [39] focussed on substance P. Despite initial demonstrations of the ability of substance P antagonists to block this neurogenic inflammation [40], ultimately they failed to translate to the clinic [41], as predicted by a lack of substance P increase in spontaneous attacks [14]. This evidence concerns the gene TAC1 and migraine disorder.