Trigeminal long-term potentiation as a cellular substrate for migraine

Most previous studies suggest that the subnucleus caudalis (Vc) of spinal trigeminal nucleus (Vsp) plays a key role in the generation and maintenance of migraine, a type of primary headache, by participating in the trigeminovascular system. Furthermore, the excitability of the Vc with the stimulation of the peripheral nociceptive fibers innervating the intracranial vessels or dura matter is regarded as a main cellular substrate for migraine. Here, a revised hypothesis is introduced, reinforcing the previous hypothesis and complementing it. This hypothesis suggests that, besides the Vc, much broader areas of the trigeminal sensory nuclei (Vsn), i.e., the principal sensory nucleus (Vp), the oralis nucleus (Vo), and the interpolaris nucleus (Vi), contribute to process and integrate pain signals generated in the head. In addition, the plasticity of synaptic transmission between nuclei or subnuclei in the Vsn, in particular, the Vsp, can be a cellular model for migraine, in the same way as the hippocampal synaptic plasticity is a model for learning and memory. This hypothesis will contribute to the discovery of new therapeutic tools for patients with migraine.