Given that (1) for the treatment of chronic migraine onabotA is injected into multiple scalp regions containing pericranial muscles and the tendons that attach them to the periosteum, and (2) of the 3 SV2 isoforms, onabotA has been shown to interact with the large intravesicular domain of SV2C but not SV2A or SV2B [27], the dense presence of SV2C (i.e., the onabotA receptors) in the periosteal axons is fundamental to our understanding of its mechanism of action in migraine prevention [16,17] and the selective attenuation of synaptic transmission in unmyelinated C-fibers [13,15,18]. Here, SV2C is linked to migraine disorder.