Advances in the pharmacotherapy of migraine. How knowledge of pathophysiology is guiding drug development.

The pharmacotherapy of migraine has advanced in parallel with our understanding of the pathophysiology of the disease. It is likely that it is the gap in our knowledge of the pathogenesis as opposed to the pathophysiology of migraine which hinders development of preventative agents. This century has seen the shift from the vascular theory of migraine pathophysiology (i.e. that cranial vessels were the prime movers in the disorder and thus vasoconstriction would be the prime treatment) to a more integrated neurovascular theory. The neurovascular theory takes the view that vascular change is secondary to neural activation, so changes such as release of trigeminal neuropeptides is predicted, has been demonstrated and suggests a possible new treatment. Similarly, it may be possible to block trigeminal nociceptive transmission in the trigeminal nucleus which might avoid the vascular adverse effects that, while small, plague current treatments. The future for migraine and cluster headache, the neurovascular headaches, is bright as we unravel their biology and this leads to further therapeutic advances.