Hypervigilance, Allostatic Load, and Migraine Prevention: Antibodies to CGRP or Receptor.

Migraine is a neurological disease affecting one in eight people. Symptoms include nausea and/or sensitivity to light and sound, and a throbbing headache. Although certain genes may increase the likelihood of migraine, environmental stimuli and molecules that increase the sensitivity of brain blood vessels and their innervations also play a role. During a migraine attack, nerves in the brain are activated, leading to increased sensitivity to stimuli, lowering the future threshold for activation, and making patients hypervigilant. Chronic, repeated exposure to certain stimuli can also lower this activation threshold, such that relatively innocuous stimuli can trigger an attack. Excessive use of certain migraine treatments can increase headache frequency over time and produce unwanted side effects; thus, selective agents are needed that specifically target the systems and pathways affected in migraine pathophysiology. Calcitonin gene-related peptide (CGRP), produced and released by nerve cells, is important in migraine pathophysiology. CGRP binds smooth muscle cell receptors, dilating blood vessels supplying the brain, and also binds to peripheral nerve cells that transmit pain signals to the spinal cord and brain. CGRP levels are elevated during a migraine attack. Medications targeting the CGRP pathway may decrease sensitivity and potentially normalize responses in hypervigilant patients. Two commercially available oral drugs that block CGRP receptors ('gepants') have reduced symptoms during migraine attacks in clinical trials. Four monoclonal antibodies (proteins that bind a specific molecule) have also been developed that target CGRP or the receptor and have been shown to significantly reduce the number of migraine days per month. Role of CGRP in Migraine.