A family member suffers from migraines so I have been reading a little around the subject.

There seem to be any number of "triggers", but I have seen mention several times of the role of histamine in migraine activation as an active area of research. The suggestion is that high histamine levels in the body can cause migraines.

Is there solid evidence that histamine can trigger migraines? How does this mechanism operate?


2 Answers 2


Yes, this is true.

Histamine is thought to induce the enzyme Nitric Oxide (NO) Synthase. NO is then available to act locally on the vasculature as a vasodilator.

NO binds to guanylyl cyclase in vascular smooth muscle cells, which leads to the production of cyclic GMP, which in turn forms phosphorylated protein kinase G. PKG phosphorylates Ca2+ channels, slowing the influx of calcium into the cell, which leads to smooth muscle relaxation, and vasodilation, which leads to migraine.

The only silver lining is that there is a check in place: with the binding of histamine to H3 receptors on c-fibers in the central nervous system, feedback inhibition prevents the further release of histamine from these sites.


Akerman S, Williamson DJ, Kaube H, Goadsby PJ. (2002). The role of histamine in dural vessel dilation. Brain Res. 956(1):96-102.

Gupta, S., Nahas, S.J.,Peterlin, B.L. (2011) Chemical Mediators of Migraine: Preclinical and Clinical Observations. Headache: The Journal of Head and Face Pain, 51(6): 1029–1045.

  • $\begingroup$ This seems to suggest that some sort of antihistamine would be effective in treating this class of migraine. Is that right? $\endgroup$
    – Poshpaws
    Commented Jul 9, 2012 at 17:36
  • $\begingroup$ @Poshpaws I didn't run across that information in any of the articles. Perhaps, but without knowing more about the affinities of the antihistamines for the different types of receptors, the drug might bind to the H3 receptor just as readily and stop that valuable feedback inhibition. $\endgroup$
    – jonsca
    Commented Jul 9, 2012 at 19:17

I've experienced migraines for 10 years, and now for the last 14 months that I've taken anti histamine medicine to see if there would be a benifit I've had good results. The frequency has dropped from approx 3 times a month to a migraine approx every 6-8 weeks. For me thats a sizeable drop. The other benifit is the severity is less intense. Now I'm trying to find why my body produces too much histamine, so I hopefully can eliminate the anti histamine med's. Recently I've greatly reduced foods with refined sugar, also processed foods, and added more whole foods, and I'm seeing excellent results.

  • $\begingroup$ james, welcome to Bio.SE. As a science-based site, and one that is NOT for medical advice (please see the first point of the FAQ ) your answer is not really what we're looking for here. Personal experience is certainly appreciated in some types of answers ("this is the protocol I use for PCR, and it works great"), but here it's not really appropriate. Ideally, for this type of question which already has a good answer, you'd add to the science being discussed, and perhaps at the end add a quick personal touch if it's warranted. $\endgroup$
    – MattDMo
    Commented Feb 4, 2013 at 21:23

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