Why Did We Evolve to Have Migraines?

Migraine is a debilitating condition that affects more than 10% of people worldwide [1]. Historically, conditions that are disadvantageous to a species decreased in prevalence to the rate of spontaneous mutation. Migraine, despite being disadvantageous to the humans who suffer from it, has not decreased in prevalence at all in the millions of years it has existed, but seems to be increasing in prevalence. With this information in mind, scientists have to suppose that there is an evolutionary advantage to migraine, either in survival or reproduction [2]. The question is — what advantage could there be? By examining the behavioral and neurological correlates of migraine, we can begin to theorize.

Trigger-Mediated Explanations

Have you ever had a headache after drinking a glass of wine? A popular theory for migraine’s evolutionary benefit is that it helps us detect toxins in our diet. There are two proposed mechanisms: if a migraineur (migraine sufferer) eats something toxic and gets a headache, they may choose to avoid the food in the future, whereas healthy people will continue to eat the food and may suffer toxic effects; or, a migraineur who eats something toxic and gets a migraine may vomit, eliminating the toxin [2]. This effect is seen in the fact that alcoholism is less common in migraineurs [3]. The effect is stronger for red wine than vodka, as it contains other molecules that may be headache triggers, most importantly histamine [4]. If less toxic food and drink makes it through the stomachs of migraineurs, it makes sense that this would favor their survival, perhaps by reducing cancer risk or preventing acute poisoning [2].

A migraine makes you want to curl up in a quiet, dark room, but why is that? Studies have begun to demonstrate that migraineurs are much more sensitive to visual, auditory, and odor stimuli than healthy controls [2,5,6], not only during migraine attacks but also between them. Interestingly, this seems to lead to an increased ability to process visual stimuli [7]. “This probably results in such behaviors as increased attention to environmental sensory stimuli such as light, noise and odors, an increased ability to detect and avoid threats in the environment, and a preference to avoid novel or unfamiliar (and therefore dangerous) environments” [2]. These behaviors could be advantageous for survival, from primitive scenarios like hunting and avoiding being hunted to modern scenarios like avoiding a car crash.

Common triggers of migraines include lack of sleep, hunger, and stress [8]. It is not hard to imagine how this could induce behavioral changes in a migraineur to include adequate sleep, regular mealtimes, and lower stress levels. It also makes sense how these behavioral changes could improve overall evolutionary fitness, both reproductive and survival. This theory has not been adequately studied, but it makes intuitive sense, so future research on the topic might help elucidate whether trigger avoidance has conferred an evolutionary benefit to migraineurs.

As a Trade-Off

Cystic fibrosis and sickle cell anemia demonstrate a “heterozygote advantage” pattern in which, while homozygotes experience a debilitating disease, heterozygotes experience few symptoms and have the benefit of being immune to malaria. It is thought that “headache heterozygotes” might experience a similar advantage with increased CNS excitability while having few to no headaches [2]. In a study of the family members of migraineurs, visual responsiveness was significantly increased, which could confer a survival advantage [9].

It is also thought that, since evolution is unidirectional, the development of our higher brain could have been constrained by existing structures like the brainstem. This is likely the reason that the brainstem is unable to suppress excessive excitatory inputs from the higher brain [2]. This mismatch between older and newer structures creates the pain that migraineurs feel but was worth the trade-off because we were able to further develop a highly evolved brain. Supporting this theory, only several instances of headaches have ever been described in another species: one great ape, an orangutan, and a dog [2,10].

Considering genetics, a single nucleotide mutation in the TRPM8 gene, a gene encoding a cation channel, has been implicated in migraine. Recently, scientists investigated the distribution of this allele among populations and found that it was much more common in people living at a high latitude – 88% in those living in Finland vs. 5% in those living in Nigeria. It seems that, in addition to increasing propensity for migraine, the mutation also conferred protection from the cold, and as such the gene was positively selected for in northern populations [11]. Scientists still do not understand why the traits became linked in the first place.

Other Theories

A final theory, which focuses on reproductive fitness, supposes that since migraine improves with pregnancy in many cases, it may have incentivized pregnancy and lactation for female migraineurs. This fits with two facts: migraine is much more common in women than men, and the highest prevalence of the disease is between the ages of 25 and 40 — also the peak reproductive period for women [2].

Conclusions & Future Research

While the evolutionary origins of migraine are still poorly understood, multiple compelling theories have emerged to explain why it might have been advantageous either in survival or reproduction. Future research should attempt to elucidate the connections between other migraine-associated genes and populations, more specifically characterize common migraine triggers, and understand the neurochemistry of migraine attacks in order to identify drug targets.

1. Walter, K. (2022). What is Migraine? JAMA, 327(1), 93. https://doi.org/10.1001/jama.2021.21857

2. Loder, E. (2002). What is the Evolutionary Advantage of Migraine? Cephalalgia, 22(8), 624–632. https://doi.org/10.1046/j.1468-2982.2002.00437.x

3. Panconesi, A. (2016, May 15). Alcohol and Migraine. American Migraine Foundation. Retrieved October 30, 2022, from https://americanmigrainefoundation.org/resource-library/alcohol-and-migraine/

4. Panconesi, A. (2008). Alcohol and migraine: Trigger factor, consumption, mechanisms. A Review. The Journal of Headache and Pain, 9(1), 19–27. https://doi.org/10.1007/s10194-008-0006-1

5. Vingen, J. V., Pareja, J. A., Storen, O., White, L. R., & Stovner, L. J. (1998). Phonophobia in Migraine. Cephalalgia, 18(5), 243–249. https://doi.org/10.1046/j.1468-2982.1998.1805243.x

6. Snyder, R. D., & Drummond, P. D. (1997). Olfaction in Migraine. Cephalalgia, 17(7), 729–732. https://doi.org/10.1046/j.1468-2982.1997.1707729.x

7. Wray, S. H., Mijović-Prelec, D., & Kosslyn, S. M. (1995). Visual processing in migraineurs. Brain, 118(1), 25–35. https://doi.org/10.1093/brain/118.1.25

8. Mayo Foundation for Medical Education and Research. (2021, July 2). Migraine. Mayo Clinic. Retrieved October 30, 2022, from https://www.mayoclinic.org/diseases-conditions/migraine-headache/symptoms-causes/syc-20360201

9. Puca, F. M., de Tommaso, M., Tota, P., & Sciruicchio, V. (1996). Photic driving in migraine: Correlations with clinical features. Cephalalgia, 16(4), 246–250. https://doi.org/10.1046/j.1468-2982.1996.1604246.x

10. Plessas, I. N., Volk, H. A., & Kenny, P. J. (2013). Migraine-like episodic pain behavior in a dog: Can dogs suffer from migraines? Journal of Veterinary Internal Medicine, 27(5), 1034–1040. https://doi.org/10.1111/jvim.12167

11. Viganò, A., Manica, A., Di Piero, V., & Leonardi, M. (2019). Did going north give us migraine? an evolutionary approach on understanding latitudinal differences in migraine epidemiology. Headache: The Journal of Head and Face Pain, 59(4), 632–634. https://doi.org/10.1111/head.13520