Chemogenetic inhibition of the posterior thalamus: Effects on migraine-like phenotypes in mice

Editor’s note: The research described below comes from a recipient of a 2024 MSC Travel Grant supporting travel to the 66th Annual Scientific Meeting of the American Headache Society. These grants reimburse travel expenses for those who have had their abstract for a presentation or poster accepted at a meeting.

By Agatha Greenway, PhD student, University of Iowa, US.

What is the research gap that your study addresses?

There is a gap in understanding of the brain regions involved in migraine. One brain region critical for migraine-like phenotypes in mice is the Posterior Thalamus (PoT). Previous research demonstrated that this brain region is sufficient to induce migraine-like symptoms in mice, including light aversion and touch hypersensitivity. We asked if the PoT is necessary for these migraine-like phenotypes.

What is your research hypothesis?

Inhibition of the PoT will rescue migraine-like symptoms of light aversion and touch hypersensitivity in mice.

What methodology did you use to address your research hypothesis?

We used DREADDs (designer receptors exclusively activated by designer drugs). This involves the injection of the designer receptor into the PoT. This receptor is exclusively activated upon peripheral injection of a designer drug and will inhibit the PoT when activated. We use a known inducer of migraine, CGRP, to induce a migraine-like state in the mice. We ran the mice in a variety of behavior assays that test for migraine-like phenotypes including light aversion and touch hypersensitivity. We chose these because light aversion is the second most bothersome symptom experienced by migraine sufferers, and touch hypersensitivity outside the face is experienced by 60% of migraine sufferers.

What are the main results of your study?

Inhibition of the PoT partially rescues both light aversion and touch hypersensitivity in mice during a migraine-like state.

What conclusions did you reach based on your results?

These results suggest the PoT is necessary for the development of light aversion and touch hypersensitivity. These data demonstrate the PoT is part of a critical brain network involved in migraine-like symptoms.

What are the limitations of your study?

Due to the partial rescues of light aversion and touch hypersensitivity, we infer that migraine-like phenotypes do not exclusively involve the PoT. This highlights the complex circuitry of migraine.

What is the relevance of your study to migraine?

The PoT and its connections could be harnessed for future targeted brain stimulation therapeutics for migraine.