Neurogenic inflammation in primary headaches

The headache in migraine is thought to result from neuronal nociceptive activity in the trigeminovascular system, that is, the meninges. In addition, trigeminal axons projecting to the meninges contain vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide and neurokinin A, that may promote, when released, plasma protein leakage and vasodilation within dura mater, characteristic of neurogenic inflammation. Thus, it has been hypothesized that a sterile neurogenic inflammation in the meninges may be involved in generating or sustaining, via occurrence of a vicious cycle, the pain accompanying the migraine attacks. We here review the evidence in support of this hypothesis as well as its potential significance in better tailoring therapies in migraine or other types of primary headaches.