Research ArticleMigraine

Neuronal PAC1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine

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Science Translational Medicine  07 Oct 2015:
Vol. 7, Issue 308, pp. 308ra157
DOI: 10.1126/scitranslmed.aaa7557

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The pain is mostly in the brain

More than just a throbbing headache, migraines also cause hypersensitivity to light and sound, nausea and vomiting, and other sensory disturbances. Exactly what goes wrong during these episodes of excruciating pain is not completely clear, and it is debated whether the salient mechanism is a peripheral or central (with the central nervous system) phenomenon. Akerman et al. now provide evidence from rats that migraine is triggered by central effects on trigeminocervical neurons and identify a therapeutic target, PAC1 receptors.

Of two similar vasodilator neuropeptides, VIP and PACAP-38, only PACAP-38 causes migraine in patients. The authors therefore compared the abilities of these peptides to induce an increase in the ongoing spontaneous firing of central trigeminovascular neurons and found that PACAP-38, but not VIP, was effective. PACAP-38 also enhanced responses to sensory stimulation, but this was independent of any peripheral changes. Of the PACAP-type receptors, only the centrally located PAC1 receptors, were able to mediate dural-nociceptive trigeminocervical neurons. Thus, migraine is likely to be triggered via PACAP-38 acting on PAC1 receptors within the brain.