Coverage from EHF 2019

Migraine treatments generally target the central nervous system (CNS) and potential peripheral targets are not investigated in depth. As part of the session entitled “New targets in migraine treatment” at the 13th annual congress of the European Headache Federation, Prof. Antoinette Maassen Van Den Brink (Erasmus University Rotterdam, Netherlands) emphasised the importance of investigating peripheral targets for migraine treatment and described the latest developments in this area.

“The periphery deserves a central role in migraine research.”

– Antoinette Maassen Van Den Brink, Erasmus University Rotterdam, Netherlands

Her presentation started with the blood-brain barrier (BBB), the semipermeable lining that ensures a tightly regulated exchange between the blood and the brain. She highlighted a study demonstrating that the trigeminal ganglion (TG) is more permeable than the brain,1 a result suggesting that some migraine treatments might have peripheral, in addition to CNS, targets. Moreover, some triptans have the potential ability of crossing the BBB and, conversely, antibodies targeting the calcitonin gene-related peptide (CGRP) are not expected to permeate this tightly regulated barrier. Combined, these observations indicate that peripheral effects of existing treatments, and the investigation of new peripheral targets for migraine treatment, is of high importance.

Prof. Maassen Van Den Brink introduced new pharmacological peripheral targets – including the receptors: amylin, PACAP/PAC1, 5-hydroxytryptamine (HT)1F, purinergic and gamma-aminobutyric acid (GABA), as well as the transient receptor potential (TRP) channels – and proceeded with an overview of the latest developments. Recent research from her laboratory has shown that lasmiditan (a 5-HT1F agonist) inhibited CGRP release in the dura mater, the TG and the trigeminal nucleus caudalis (TNC). The efficacy of 5-HT1F agonists might, therefore, have both CNS and peripheral components. As for purinergic receptors, the P2X receptor mediates vasocontraction and induces CGRP release.2 This receptor is expressed in the meningeal artery and the TG, and antagonists of the P2X3 receptor in particular, might be a viable new class of migraine treatment. Prof. Maassen Van Den Brink highlighted that while TRPV1, a member of the TRP channels, failed to show promising results in the clinic, these ion channels remain interesting targets.3 While only a few of the new peripheral targets were discussed during this presentation, there is much promise in this emerging field of migraine research.

References

  1. Eftekhari S, et al. Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood-brain barrier. Brain Res. 2015;1600:93–109.
  2. Haanes KA, et al. Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models. Cephalalgia. 2019;in press.
  3. Benemei S, et al. TRP channels and migraine: Recent developments and new therapeutic opportunities. Pharmaceuticals. 2019;12:e54.