Action mechanisms of Onabotulinum toxin-A: hints for selection of eligible patients

In the past few decades, the so-feared botulinum toxin has conversely acquired the role of a ever more versatile therapeutic substance, used in an increasing number of pathological situations, including chronic headache and more precisely in the prophylaxis of chronic migraine. The medical use of botulinum toxin allowed to better understand its multiple mechanisms of action. Investigations about the pathophysiology of primary and secondary headaches has shown a series of common biological elements that frequently are also targets of the action of botulinum toxin. These increasing evidences allowed to identify some biochemical, neurophysiological and radiological markers that may be useful in the individuation of patients which probably will respond to the treatment with Onabotulinum toxin-A among chronic migraineurs. These predictors include CGRP plasmatic levels, specific laser-evoked potential responses, peculiar brain MRI and fMRI and characteristic clinical manifestations. Unfortunately, at now, these predictors are still not available for the clinical practice. Furthermore, the better knowledge about biology of headaches and regarding botulinum toxin activities may also help in directing investigations on the possible use of Onabotulinum toxin-A in other headaches different from migraine. This review tries to show in detail these biological mechanisms and their implication in selecting patients eligible for the treatment with Onabotulinum toxin-A.