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It is generally-accepted that headaches are a common side effect from receiving the COVID vaccine.

Vaccine recipients with pre-existing immunity experience systemic side effects with a significantly higher frequency than antibody naïve vaccines (e.g., fatigue, headache, chills, fever, muscle or join pains, in order of decreasing frequency, P < 0.001 for all listed symptoms, Fisher’s exact test, two-sided).

— Florian Krammer et al.: "Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine" doi: https://doi.org/10.1101/2021.01.29.21250653

I am trying to understand why. What theories or known biological, immunological or otherwise physiological mechanisms would cause recipients of the vaccine to report headaches as a common side effect?

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  • $\begingroup$ Headaches are a side effect of both vaccinations and infections. Have a look at the effects of cytokines, particularly Interferons. $\endgroup$
    – Polypipe Wrangler
    Mar 31, 2021 at 21:46

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Headache is one of the various side-effects of vaccination. Typically, a person will have pain in the site of injection, muscles throughout your body and head.

The immunological reason is the network of our immune system. Whenever a foreign antigen (vaccine) is detected by our immune system, antigen-presenting-cells (macrophages, dendritic cells) takes the antigen to nearest lymph nodes where it is presented to the adaptive immune system. Due to this invasion, strong immune response starts which leads to the pain.

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Image Source: wikipedia.org/wiki/Lymphatic_system

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  • $\begingroup$ Thanks for the amazing answer @Riq (I would upvote you +1 but I don't have enough rep!) -- one quick followup question for you, if you don't mind. It sounds like you're saying that when cells, such as macrophages, present lymph nodes with antigens (from the vaccine) this initiates an immune system response, which you say leads to "pain". But why headaches? Why is this pain so specific to the head? Thanks for any clarification! $\endgroup$
    – IamYourFaja
    Mar 26, 2021 at 12:43
  • $\begingroup$ BTW I am not the one who gave you a downvote! I am happy with your answer so far! $\endgroup$
    – IamYourFaja
    Mar 26, 2021 at 12:54
  • $\begingroup$ @IamYourFaja You can accept the answer if you think it answered your question. $\endgroup$
    – Riq
    Mar 29, 2021 at 4:19
  • $\begingroup$ Yes thanks again @Riq, do you have any ideas regarding my followup question above ("But why headaches?...") Perhaps something to do with the cytokines and interferons that Polypine mentioned? $\endgroup$
    – IamYourFaja
    Mar 29, 2021 at 11:50
  • $\begingroup$ @IamYourFaja yeah, cytokines are essentially the communicator of our immune system. They help in cell signaling and involved in various side effects of our immune system. Hope this clarifies your follow-up question. $\endgroup$
    – Riq
    Apr 1, 2021 at 21:56

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