Chronic migraine causes more severe gut inflammation and CGRP elevation than episodic migraine in mice | Research

The takeaway

Chronic migraine mouse models showed more severe gut-brain axis dysregulation than episodic migraine, with elevated gut CGRP levels, shortened colons, increased inflammatory cytokines, and distinct immune cell infiltration patterns.

CGRP elevated in gut
Chronic migraine mice had elevated gut CGRP alongside colon shortening and immune cell infiltration—linking neuropeptide biology to GI comorbidities

What the researchers found

CM vs EM: CM showed shortened colon length, elevated gut CGRP, increased inflammatory cytokines, and enrichment of T cells, Tregs, and macrophages in distal colon. EM showed increased dendritic and B cell populations. Both reduced food intake and body weight.

Why it matters

CGRP is already the target of major migraine drugs (erenumab, fremanezumab). Finding that CGRP is elevated in the gut during chronic migraine—and that GI damage differs between migraine types—suggests CGRP-targeting drugs may have gut-protective benefits and that gut health could influence migraine management.

How the study worked

NTG-induced mouse models of EM (single injection, N=15) and CM (repeated injections over 9 days, N=15). GI tissue analysis for morphology, cytokines, CGRP levels, and immune cell profiling.

What this study cannot tell us

Mouse model—NTG-induced migraine is a simplified model. CGRP elevation in gut may be a consequence rather than cause of GI damage. Small group sizes. No therapeutic intervention tested.

How to read the evidence

Preclinical mouse study with comprehensive GI analysis. Good mechanistic evidence but limited to NTG-induced migraine model.

When this study was published

Published in 2025.

The bigger picture

This study strengthens the gut-brain axis connection in migraine and suggests that the neuropeptide CGRP plays a role in both brain and gut manifestations of the disease. Anti-CGRP therapies may benefit both symptoms simultaneously.

Questions still open

Do anti-CGRP migraine drugs improve GI symptoms in chronic migraine patients?
Could gut microbiome interventions reduce CGRP-mediated gut inflammation in migraine?
Are GI comorbidities in migraine patients driven by peripheral CGRP?

Common questions

Why do migraine patients often have stomach problems?

This study shows that the neuropeptide CGRP—which causes migraines in the brain—is also elevated in the gut during chronic migraine, causing inflammation, immune changes, and gut damage. This gut-brain connection explains why many migraine patients experience nausea, abdominal pain, and other GI symptoms.

Could migraine drugs help with gut problems too?

Potentially. Since anti-CGRP drugs (like erenumab) block the same peptide that causes gut inflammation in this study, they might improve GI symptoms alongside migraine prevention. This needs to be studied in patients, but the biological rationale is strong.

Read the original research

Distinct Gut-Brain Axis Dysregulation in Episodic Versus Chronic Migraine: Insights from NTG-Induced Mouse Models.

International journal of molecular sciences, 26(21)

View on PubMed ↗Publisher’s paper ↗

Citation

Shin, Dae-Chul; Jung, Harry; Park, Songyi; Song, Dan-Gyeong; Lee, Sang-Hwa; Sohn, Jong-Hee. (2025). Distinct Gut-Brain Axis Dysregulation in Episodic Versus Chronic Migraine: Insights from NTG-Induced Mouse Models.. International journal of molecular sciences, 26(21). https://doi.org/10.3390/ijms262110493