Fig. 7

Schematic overview of the possible modulation by C-fibers on adjacent Aδ-fibers through axon-axon signaling at nodes of Ranvier in the trigeminal system. CGRP is released from the C-fiber bouton and diffuses into the node of Ranvier. Activation of the CGRP receptor causes increase in cyclic AMP, which could alter the conductivity of Na⁺ or K⁺ channels through Phosphokinase A (PKA). Furthermore, there is a possibility that 5-HT receptors could negatively modulate the cyclic AMP at the node. Alterations in Na⁺ or K⁺ channels could modulate the nodal threshold of activation. The schematic also includes a hypothesis on the mode of action of the anti-migraine antibody treatments