Bench to bedside understanding of migraine pathophysiology

Abstract

Migraine is a common, complex brain disorder whose pathophysiology is being unravelled by bench to bedside and back iterative advances [ [1] Goadsby P.J. Holland P.R. Martins-Oliveira M. Hoffmann J. Schankin C. Akerman S. Pathophysiology of Migraine- A disorder of sensory processing. Physiol. Rev. 2017; 97: 553-622 Google Scholar ]. Migraine consists of overlapping, parallel “phases” that offer insights into brain areas for laboratory exploration. Pain in migraine involves the activation, or perception of activation, of the pain-producing innervation of intracranial structures, notably the dura mater. The first, ophthalmic division, can be activated by direct stimulation in experimental animals to activate pathways of potential interest. Second order activation occurs in the trigemiinocervical complex that projects, with decussation, in the quintothalamic tract to the neurons of the ventroposteromedial thalamus. Triptans, serotonin 5-HT1B/1D receptor agonists, gepants, calcitonin gene-related peptide (CGRP) receptor antagonists, and ditans, 5-HT1F receptor agonists, each reduce nociceptive signalling in this pathway, and are effective in the acute treatment of migraine. Blockade of the pathway with monoclonal antibodies directed at the peptide, or its canonical receptor, are effective in the preventive treatment of migraine. Remarkably, gepants can have both acute attack effects and preventive effects in migraine. Brain imaging has demonstrated activations in the region of the hypothalamus in migraineurs in the premonitory phase in nitrogylcerin-triggered attacks or in spontaneous attacks. Given premonitory symptoms such as somnolence, yawning, thirst and polyuria, diencephalic structures offer a target for further bench-based studies. Understanding migraine neurobiology has generated new therapies and is likely to continue to do.