Journal article
Early life stress induces brain-wide electrical network predisposition to migraine
Journal of headache and pain
06/13/2026
DOI: 10.1186/s10194-026-02399-8
PMID: 42288719
Abstract
Migraine is a disorder of severe, recurrent headaches and debilitating sensory, cognitive and affective symptoms, often triggered by stress. Early life stress in childhood has been shown to increase the likelihood of migraine in adulthood in humans. Calcitonin-gene related peptide (CGRP) has been shown to reliably and acutely induce migraine or migraine-like behavior in both humans and rodent models. Here we investigate the impact of early life stress and CGRP on migraine-related neural circuitry in order to better understand the mechanisms by which early life stress predisposes neural circuitry to migraine brain network activity.
We implemented an early life stress paradigm in the outbred strain of mice, CD1. We evaluated the impact of peripheral CGRP on migraine-like behavior and employed multi-site in vivo neurophysiology in freely behaving mice. A changepoint analysis was used to dissect differences in individual CGRP-induced responses.
We found that early life stress exacerbated migraine-related behavioral and network physiology. CGRP alone caused disruptions in neural oscillatory activity across a network of brain regions including the anterior cingulate cortex (ACC), amygdala (AMY), thalamus (Po, VPM, and MDthal), and parabrachial nucleus (PBN). We found that power across the network was lowered within 10 minutes of peripheral CGRP exposure, which was sustained for ~40-50 min. Coherence was mostly disrupted in amygdalar brain region pairings, and took on a shorter timecourse, with partial rescue of these responses by migraine abortive, sumatriptan. We found that early life stress exacerbated most of these responses, especially AMY-thalamic coherence pairings, although early life stress in the absence of CGRP demonstrated no impact on the network overall. We further identified individual mice with brain-network activity hypersusceptible to migraine.
Our findings demonstrate that early life stress confers vulnerability to migraine, simultaneously impacting behavior and brain network activity responses to peripheral CGRP.
Details
- Title: Subtitle
- Early life stress induces brain-wide electrical network predisposition to migraine
- Creators
- Micah Johnson - University of IowaMaureen Eberle - University of IowaIan Hultman - University of IowaXinyu Zhang - Department of Statistics and Actuarial Science, University of Iowa, Iowa City, IA, USAYassine Filali - University of IowaBenjamin Hing - University of Iowa, Molecular Physiology and BiophysicsMolly Matkovich - University of IowaAlli Jimenez - University of IowaSara Mitchell - University of IowaAnjayooluwa Adegboyo - University of Maryland, Baltimore CountyRadha Velamuri - University of IowaJulia Miller - University of IowaKung-Sik Chan - University of Iowa, Statistics and Actuarial ScienceSanvesh Srivastava - University of Iowa, Statistics and Actuarial ScienceRainbo Hultman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of headache and pain
- DOI
- 10.1186/s10194-026-02399-8
- PMID
- 42288719
- NLM abbreviation
- J Headache Pain
- ISSN
- 1129-2377
- eISSN
- 1129-2377
- Publisher
- Springer Nature
- Language
- English
- Electronic publication date
- 06/13/2026
- Academic Unit
- Statistics and Actuarial Science; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Biochemistry and Molecular Biology
- Record Identifier
- 9985175467102771
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