New Study Highlights GABAergic Neuron Loss in Chronic Migraine

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PASADENA, Calif. — November 20, 2025 — A new preclinical study led by researchers at Huntington Medical Research Institutes (HMRI) finds that male—but not female—rodents in a chronic migraine model show selective loss of GABA (inhibitory) neurons across key pain- and emotion-related brain regions.

Published in the journal The Journal of Headache and Pain, the study:

  • - Used nitroglycerin-triggered models of chronic migraine in GAD65-GFP transgenic mice and rats, assessing the locus coeruleus, amygdala, hippocampus, and neocortex.

  • - Found a significant reduction of GAD65-GFP positive GABAergic neurons in males treated with NTG compared to saline controls, but no such reduction in females.

  • - Identified elevated neuronal activation marker ΔFosB, increased apoptosis (active caspase-3), and up-regulation of stress-related neuropeptides PACAP/PAC1 and BDNF/TrkB in male subjects.

  • - Observed down-regulation of GABA-signaling genes in the choroid plexus (NKCC1 overexpressed) in males, pointing to broader neuro-immune/ion-homeostasis contributions.

The authors conclude that this sex-specific vulnerability of inhibitory circuits may help explain migraine chronification and associated cognitive/emotional comorbidities in males, and that tailored therapeutic strategies may be warranted.

Full article: The Journal of Headache and Pain, November 2025