TY  - JOUR
T1  - Chickenpox as An Evolutionary Trigger for Migraine: A Hypothesis 
AU  - Rozen, Ethan M.
AU  - Rozen, Lincoln E.
AU  - Rozen, Todd D.
JF  - Exploratory Research and Hypothesis in Medicine
VL  - 11
IS  - 4
SN  - 2472-0712
SP  - e00055
EP  - e00055
Y1  - 2026-10-30
DO  - 10.14218/ERHM.2026.00055
UR  - https://www.xiahepublishing.com/2472-0712/ERHM-2026-00055
AB  - On the surface there does not appear to be a connection between chickenpox and migraine but, on closer examination, both conditions are associated with neuroinflammation and, because almost every human throughout history was infected with the varicella-zoster virus, it is possible that it could have triggered certain medical disorders in our ancestors. We propose a hypothesis that the acute chickenpox infection may have contributed to the appropriate environment to prime the brains of early humans for migraine. Several inflammatory mediators and immune cells involved in migraine also participate in the immune response to primary varicella infection. This, together with the fact that the virus establishes chronic latency in the trigeminal ganglia, may have contributed to a sensitized trigeminovascular system that could produce migraine if the correct susceptibility genes and exposures were present. These postinfectious neuroinflammatory reactions would also have the capability of producing a hyperexcitable cortex, hypothalamic generator and cortical spreading depression, which are the key components of migraine pathophysiology. Other supporting observations include the coexistence of varicella-zoster virus and migraine in early humans, the fact that chickenpox occurs prior to the age of migraine onset in most individuals, and the recent recognition that the proportion of US migraine patients with moderate-to-severe disability rose from 22.0% to 42.4% following implementation of the varicella vaccination program. We propose that chickenpox may have acted as an evolutionary trigger for migraine.