Figure 2.

Speculative mechanism(s) of BoNT action. BoNT injected into cranial dermatomes will be taken up by the cutaneous sensory afferents (CSA) and transported retrogradely to the TG where it cleaves SNAREs and is then transported centrally to TNC. Transported BoNT may undergo a trans-synaptic movement either at the second-order neuron (which receives convergent input from the meningeal afferent) or the terminal of the converging activated meningeal afferent. Such a trancytosis may also hypothetically occur in TG sensory neurons and block the activated meningeal afferent release. Future experiments are required to address these options.