Effectiveness of BoNT‐A in the Treatment of Migraine and Its Ability to Repress CGRP Release

Botulin toxin type A (BoNT-A) has been demonstrated as an effective prophylactic treatment of primary headache disorders.1 The results of the experimental studies of Durham et al suggested that the efficacy of BoNT-A in the management of migraine is due, in part, to its capacity in blocking the release of calcitonin gene-related peptide (CGRP) from the trigeminal neurons.2 In his commentary, Blumenfeld pointed out that other studies showed that BoNT-A inhibits the release of substance P and glutamate neurotransmitters responsible for nociception.3 Therefore the nociceptive effect of BoNT-A may, in part, be explained by an inhibitory mechanism of neurotransmitters of nociceptive neurotransmission from the periphery to the cortex. In our previous articles we had referred the hypothesis that therapeutic blockade of greater occipital and supraorbital nerves “might have resulted in an inhibition of the constant trigeminal hyperexcitability present in headaches by not only locking the conduction of the noxious stimuli but also by blocking the antidromic flow of substance P and CGRP, mediators of axon reflexes that are the basis for perivascular neurogenic inflammation. The consequent vasodilatation and the extravasation of the above peptides, local reinforcing factors of the algogenic stimulation might have been interrupted by the anesthetic with subsequent normalization of the response threshold to the stimuli of the nociceptors.”4 The action of inhibition of axonal transport of local anesthetic had long been shown.5,6 Repeated anesthetic blocks could produce a long-lasting effect of hypostimulation on the peripheral nociceptors, thus rebalancing their threshold of activation and consequential arrest of induction of neuroplastic mechanism of central hypersensitization that may clinically produce chronicity of pain. This course of multiple anesthetic blockade of nerves, even if it is purely without any influence of the “primum movens,” would interfere in the central pathogenetic mechanism of the formation and transmission of the trigeminal nociceptive stimulus of a migraine crisis.7 The observations published by Durham et al are of great interest and very stimulating, and can be applied similarly to local anesthetics. It can also partly confirm the eventual common pharmaco-dynamic mechanism of the two substances like BoNT-A and local anesthetic and explain the clinically demonstrated efficacy of their use in migraine. I would like to ask Dr. Durham if his elegant experiment could be applied to local anesthetics. The valid experiments supported by encouraging clinical observations can open new and interesting clinical horizons in the treatment and prophylaxis of migraine also in its chronic form. Claudio A. Caputi, MD Ospedali Riuniti Umberto I, Medicine of Pain and Palliative Care/Ancona, Italy