Prior research has shown that when people have a migraine, there are increased levels of the neuropeptides VIP and PACAP in their blood, suggesting their presence may be a cause.
 
To find out if that is true, the researchers administered each to test rats while monitoring both blood vessels and neurons that are known to be involved in headaches. They found that both caused the blood vessels to widen, but only one, PACAP caused an increase in neural activity, fingering it as the real culprit in causing migraines.
 
To relieve the neural activity they had instigated, the researchers fed a compound known to block the receptors that PACAP binds to (PAC1), but that did not work, so they injected it directly into the rats' brain, and that did cause the over-active nerves to quiet.
 
At this point, it is still not known if the results the research pair found apply to humans, and it will be difficult to find out—it is not really possible to inject drugs directly into a patient's brain.
 
Further research will thus have to be directed at finding a way to carry a compound through the blood-brain barrier that can reach the over-active nerves and to find out what causes PACAP levels to rise in the first place.
 
http://stm.sciencemag.org/content/7/308/308ra157