IHC 2021 | Soluble guanylyl cyclase pathways in regulating migraine-associated pain

We’re very excited about that presentation because it was for the Cephalalgia award, which was given to us by the editors of Cephalalgia. That was a really fun study that we did in collaboration with some medicinal chemists here at the University of Illinois at Chicago. It was basically to sort of try to understand how it is that the known human migraine trigger nitroglycerin. What are the different pathways that may be involved with how it causes migraine? And the reason that we studied it is because we know that nitric oxide signaling pathways are known to initiate migraines in people. But the thing is, is that nitric oxide can also produce a reactive oxygen species, which may also contribute to a headache. And so the thing that we did in this study was to specifically look at whether activation of the nitric oxide and soluble guanylate cyclase pathway were the direct mechanisms through which nitric oxide may be causing migraine.

And what we did was to use a novel soluble guanylate cyclase activator, VL102. And we found that essentially this compound, which circumvents nitric oxide altogether, it just basically binds to the only known receptor of nitric oxide within the body, and what we found was that VL102 basically caused the same types of cephalic allodynia that something like nitroglycerin or sildenafil would also cause. And that this allodynia was blocked by triptans, so acute migraine therapies, as well as preventive migraine therapies. And that also long-term treatment with VL102 or the soluble guanylate cyclase activator increased CGRP expression within the trigeminal ganglia. Again, really pointing at this idea that this nitric oxide soluble guanylate cyclase pathway may be very important when it comes to the initiation and maintenance of migraine.