Searching for the “Weak Link” in Migraine

“Weak link” may work for a headline, but investigating and treating migraine is much more complex, because the body is incredibly complex. Think of a spider web. Or better, a whole city with all its roads and businesses and families.

At first, it may seem that widening a particular road is the answer. After all, a certain number of cars travel down this road, so if it were double the size, the traffic would flow much quicker. Right? Well, of course you know it’s not that simple. To widen the road, you take land from something else. You encourage more people to use that route. You spend months in construction, changing people’s habits.

So we hear about various drugs that have different effects on the body. A beta-blocker. CGRP inhibitors. Cox-2 inhibitors. They’re all trying to fix a certain street – not to simply improve the traffic on that road, but to fix a city-wide problem. Migraine symptoms.

There has been some interesting research recently on one of these “roads” in your body – hyperpolarization-activated cation channels (actually a family of proteins in the heart and nervous system). This particular communication path in your body has a lot to do with inflammation. In fact, if you check out this study from several years ago, you might notice several words familiar to the migraine world – inflammation, hypersensitivity, and the temporomandibular joint. That last one is your jaw joint – the joint and nerves in the face are often implicated in migraine related headache pain.

So if this channel is part of the system that communicates inflammation and neuropathic pain, would this be a good “road to repair” in order to fight migraine? And how would you test that hypothesis?

A study in Denmark is trying to do just that. How? Well, we already have a hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel blocker, called ivabradine (sold under the brand names Corlanor, Procoralan, and others). So the study will be testing ivabradine, not necessarily as a future migraine treatment itself (although that may be the case), but to see how effective it is. If effective, researchers may look at developing this type of medication specifically for migraine use.

It is interesting that ivabradine is a heart medication. It’s currently used to slow the heart rate in patients with certain types of chest pain or heart failure. There are several other heart medications that are used for migraine – such as beta blockers (think of metoprolol, propranolol, and timolol). In fact, patients that don’t respond well to beta blockers are sometimes given ivabradine.

To read more about the hypothesis and theory behind this clinical trial, just go to the trial page and look specifically at the “Detailed Description” – The Effects of Ivabradine on Levcromakalim-induced Migraine (ILMO). To go deeper into HCN channels, this article is from a few years ago but will give you an introduction: Hyperpolarization-Activated Cation Channels: From Genes to Function