The Pathophysiological and Pharmacological Basis of Current Drug Treatment of Migraine Headache

Doodipala Samba Reddy


Expert Rev Clin Pharmacol. 2013;6(3):271-288. 

In This Article

Inflammation & Pain Pathway

The endogenous processes that promote meningeal inflammation and pain remain unclear. It is thought that neurogenic inflammation is produced by the release of vasoactive proinflammatory factors following activation of specific nociceptors or by CSD or other triggering mechanisms.[21,22,45] There is evidence that CSD can activate fibers of the trigeminal nerve, which in turn may cause central sensitization and parasympathetic activation. Thus, it is thought that CSD is the common mechanism triggering migraine.

The end result of vascular and/or neural disturbances is inflammation. The trigeminal nerve, a major nerve that collects and transmits signals to the face and head, becomes activated by local inflammation, causing nerve fibers to become painfully sensitive to stimulation. As the migraine develops, it is evident that sensitivity to pain signals arriving from peripheral nerves increases in central pain neurons in the spinal cord and brain stem (migraine generator), a phenomenon known as 'central sensitization' that may ultimately be responsible for symptoms of migraine headaches.[8,10,21,22,31,32] Depolarization of trigeminal C-fibers is thought to release substance P, which produces platelet aggregation with resultant 5-HT and thromboxane A2 release. This activates prostaglandin and kinin production, leading to neurogenic inflammation. The throbbing pain of migraine is thought to be caused by the swelling of the dura, which has embedded blood vessels and pain-sensitive nerve fibers.