Calcitonin Gene-Related Peptide and Migraine: Implications for Therapy

It is clearly evident from the literature that headache has troubled mankind from the dawn of civilization (Rapoport & Edmeads, 2000). A variety of methods have been used throughout the ages in an attempt to alleviate or cure this pain; these may have been the most appropriate at that time, and were probably seen as “cutting edge”. Today they seem at best amusing, and at worst cruel and barbaric. The earliest concepts in migraine were those of the supernatural, with migraine believed to be due to malevolent beings within the head; treatment based on this idea included incantations and application to the head of substances intended to drive out the demons and spirits (Edmeads, 1991). These were also driven out physically, as in the Neolithic period (8500-7000 BC). The people living in this time used the method of trepanation, a kind of neurosurgery, which involved removing circular chunks of skull so that the spirits causing the headache could escape. Over 50% of the trepanned skulls have shown evidence of healing, indicating a high survival rate for this operation. Although the scientific rationale behind trepanation is not understood, it is surprising that this procedure was performed as a treatment for migraine as late as the mid 17th century (Edmeads, 1991; Rapoport & Edmeads, 2000).