Adenosine is a purinergic signaling molecule with a wide range of physiological functions. Studies have shown that adenosine infusions can induce headache, and adenosine receptor antagonist, caffeine, relieves migraine headache. Janu Thuraiaiyah, MD, PhD, Danish Headache Center, University of Copenhagen, Glostrup, Denmark, discusses the findings of a randomized, double-blinded, placebo-controlled, crossover study assessing the difference in the incidence of migraine attacks after adenosine compared to placebo. A total of 18 participants diagnosed with migraine without aura received an infusion of adenosine or placebo over 20 minutes. Headache intensity, migraine-associated symptoms, vital signs, the diameter of the superficial temporal artery (STA), and blood flow velocity in the middle cerebral artery (VMCA) were measured at baseline and every 10 minutes until two hours post-infusion start. Results showed no difference in the incidence of migraine following adenosine compared to placebo, but the incidence of headache after adenosine compared to placebo was statistically significant. Additionally, adenosine increased STA diameter and decreased VMCA compared to placebo. Together those findings suggest that adenosine causes short-lasting vasodilation and headache, but not migraine attacks in migraine patients. This interview took place at the 16th European Headache Congress (EHC) in Vienna, Austria.
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Transcript (edited for clarity)
So adenosine is a naturally occurring purinergic nucleoside that occurs in human body. And previous studies showed that infusion of adenosine can cause headache for cardiac investigations. And also we know that caffeine can, for one, it can trigger migraine attacks, but at the same time, in combination with simple energetics, caffeine is also able to treat migraine attacks. So based on these observations, we have hypothesized that giving adenosine as an infusion to migraine patients might actually induce migraine attacks...
So adenosine is a naturally occurring purinergic nucleoside that occurs in human body. And previous studies showed that infusion of adenosine can cause headache for cardiac investigations. And also we know that caffeine can, for one, it can trigger migraine attacks, but at the same time, in combination with simple energetics, caffeine is also able to treat migraine attacks. So based on these observations, we have hypothesized that giving adenosine as an infusion to migraine patients might actually induce migraine attacks. So to investigate this, we conducted this randomized placebo control crossover study in which our primary endpoint was to investigate in the incidence of migraine attacks following adenosine compared to placebo. So 18 patients were included in the study and they were randomized to receive either adenosine infusion, a 20 minute infusion or saline for a 20 minute infusion on two separate days with a seven days washout period.
And this was of course done in a crossover manner. So they went through both saline and adenosine on two separate days. And during the infusion and after the infusion for every 10 minutes, we asked the patient regarding their headache characteristics. Vital signs were measured and we also measured the diameter of the superficial temporal artery and the velocity of the blood flow in the middle cerebral artery. When patients were discharged, they were given a headache diary that they had to fill out at home and then send in to us, of course to see if there was anything in the time that they were discharged afterwards for a period of 12 hours post-infusion. Yeah, so a total of 18 patients were included in the study and randomized both saline and adenosine infusion. And what we found was that seven out of these 18 patients reported migraine attacks after the adenosine infusion compared to three patients after the placebo infusion.
However, this was not statistically significant. At the same time, the induction rate of headache itself, so not migraine, but any kind of headache, was shown to be present in 14 patients out of the 18 following adenosine. And then in six patients following the placebo infusion. And this was statistically significant. So this is just the headache and the migraine induction rates. If you then look at the vessels, we found that there was a short lasting dilation of the superficial temporal artery and a decrease, again, short lasting decrease in the velocity of the blood flow in the middle cerebral artery. Which you might say that it’s an indirect way of saying there is a dilation, but there’s other aspects of course that need to be considered as well. So we cannot say that for sure. So overall, in conclusion, we found that adenosine does induce headache in migraine patients, but not migraine in migraine patients. And our inability to see that it could induced migraine attacks in migraine patients could be due to the counteracting effect of the adenosine receptors. So therefore, future studies again should focus on the adenosine receptors rather than just adenosine as a compound.