Effect of vasoactive intestinal polypeptide on development of migraine headaches

1. Vasoactive intestinal polypeptide may play a key role in the mechanism of migraine pathogenesis.

2. Drug therapies targeting vasoactive intestinal polypeptide receptors may be beneficial for treating migraines.

Evidence Rating Level:  1 (Excellent)

The pathophysiology of migraines is an intricate and complex process that is not yet fully understood. However, it is known that when the trigeminovascular system is activated, vasoactive peptides are released by afferent and efferent nerve fibres. In simplistic terms, these vasoactive peptides play a role in the signalling cascade leading to migraines. Additionally, these migraines are often associated with dilation of the superficial temporal artery (STA) and the middle meningeal artery (MMA). This study aimed to investigate the role of vasoactive intestinal polypeptides (VIP) as they are currently the only peptide known to cause arterial dilation without inducing migraines. In order to test the effects of VIP, a randomized, double-blind, placebo controlled, crossover study was conducted in Denmark.  Participants (n=21) between the ages of 18-40 with a diagnosis of migraines without aura were recruited. Participants were then randomly assigned either a sterile saline placebo or VIP 8pmol/kg/min to be infused over the course of 2 hours. Participants were monitored for signs of headaches, migraines, diameter of the STA, cranial autonomic parasympathetic symptoms (CAPS), blood pressure, and asked to keep a diary of all symptoms over 12 hours. Out of the total cohort, n=15 (71%; 95% CI) developed migraine attacks after VIP treatment. This was compared to the placebo where only 1 patient (5%; 95% CI) experienced a migraine (P < .001). Participants who received the VIP also experienced more nausea, photophobia, increase in STA diameter, and increased heart rate compared to placebo. The study concluded that among participants with migraine without aura, a 2-hour infusion of VIP induced migraines at a rate of 71%. Previous studies have investigated the impacts of VIP but with smaller doses and time intervals. In contrast, a strength of this study was the long duration of the infusion. The two hours of infusion allowed for long-term dilation of the STA which may be key in understanding the pathogenesis of migraine attacks. On the other hand, the study’s cohort size was relatively small and future studies may wish to expand the trial to include more participants including those without prior diagnoses of migraines. Overall, the results of this study may have important treatment impacts as VIP antagonists may be a potential drug therapy for migraine attacks.

Click to read the study in JAMA Network Open

Image: PD

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