Steroids Increase CGRP Levels in Migraine Nerve Tissue — But Don't Cause Pain | Research

The takeaway

Dexamethasone increased CGRP and its receptor expression in trigeminal ganglia, but this upregulation did not trigger head pain in rodents.

No allodynia
Despite increased CGRP and receptor expression, corticosteroids did not trigger head pain in rodents

What the researchers found

Corticosteroids upregulated CGRP and receptor expression in the trigeminal system but did not induce head pain, challenging simple CGRP-pain assumptions.

Why it matters

This paradoxical finding — more CGRP without more pain — deepens our understanding of what actually triggers migraine and how steroids help.

The numbers in context

Dexamethasone increased CGRP and RAMP1/CLR expression in rat CA77 cells, SHSY-5Y cells, and human PBMCs. Betamethasone 320 mcg/kg for 10 days in rats and mice. No cephalic allodynia despite increased CGRP.

How the study worked

In vitro (cell cultures: CA77, SHSY-5Y, human PBMCs) and in vivo (rat) study examining dexamethasone effects on CGRP/RAMP1/CLR expression.

Who was studied

Cell cultures and rodents treated with corticosteroids

What this study cannot tell us

Rodent model — pain assessment in animals has inherent limitations. Acute steroid exposure may differ from chronic clinical use.

How to read the evidence

Combined in vitro and in vivo preclinical study — robust methodology for mechanistic questions, limited clinical translatability.

When this study was published

Published in 2025, contributing new insights to the CGRP-migraine mechanism debate.

The bigger picture

Challenges the oversimplified view that CGRP elevation equals migraine, suggesting additional factors are needed to translate CGRP signaling into pain.

Questions still open

If steroids increase CGRP, what other mechanism explains their headache benefit?
What cofactors are needed alongside CGRP elevation to trigger migraine?

Common questions

Do steroids affect CGRP levels?

Yes — this study shows dexamethasone increases CGRP and its receptor expression in migraine-relevant nerve tissue.

If CGRP causes migraine, why didn't increased CGRP cause pain?

This finding suggests CGRP elevation alone isn't sufficient for migraine — other factors likely need to be present to trigger pain.

Read the original research

Corticosteroid-dependent increased expression of CGRP and its receptor subunits within the rodent trigeminal ganglion does not prompt cephalic allodynia.

Cephalalgia : an international journal of headache, 45(11), 3331024251367043

View on PubMed ↗Publisher’s paper ↗

Citation

Pistolesi, Alessandra; Tuniz, Simone; Lapucci, Andrea; Molli, Alice; De Cesaris, Francesco; Landini, Lorenzo; Nassini, Romina; Buonvicino, Daniela; Chiarugi, Alberto. (2025). Corticosteroid-dependent increased expression of CGRP and its receptor subunits within the rodent trigeminal ganglion does not prompt cephalic allodynia.. Cephalalgia : an international journal of headache, 45(11), 3331024251367043. https://doi.org/10.1177/03331024251367043