The locus coeruleus is involved in processing pain in migraine

According to an animal study, the brainstem locus coeruleus modulates nociceptive processing and could be involved in a bidirectional sleep-headache relationship.

In a study in laboratory animals, which aimed to assess the role of the locus coeruleus in migraine-related pain processing, C57Bl/6J mice received either a stereotaxic injection with the CAV-PRS-hM3Dq-mCherry canine adenovirus or a control administered directly to the locus coeruleus [1]. “This virus contained a noradrenergic specific PRS promoter in order to drive DREADD [Designer Receptors Exclusively Activated by Designer Drugs] expression exclusively within these noradrenergic neurons,” said Dr Veronica Munday (King’s College London, UK). The DREADD used for the study was hM3Dq, a modified human muscarinic 3 receptor that does not respond to endogenous ligands, “but which can be activated by the designer ligand clozapine N-oxide.”

At the 60- and 90-minute timepoint after administration of clozapine N-oxide, mice in the control group had stable 50% mechanical activation thresholds, while mice who received the excitatory DREADD had significantly increased thresholds (P<0.05 at both timepoints). “This result suggests that activation of the locus coeruleus has a potential nociceptive effect,” said Dr Munday. The results were further assessed in a nitroglycerin model of induced cutaneous allodynia. Following nitroglycerin administration, there was a significant decrease in 50% mechanical activation thresholds, which reverts to baseline values after clozapine N-oxide administration.

“Overall, activation of the locus coeruleus can modulate nociceptive processing and is potentially nociceptive,” said Dr Munday. “This highlights that the locus coeruleus is a key region in migraine processing,” she continued, adding that the next steps involve assessing the role of the locus coeruleus in migraine-related sleep alteration and determining the specific pathways through which the locus coeruleus is involved in migraine and sleep.

1. Munday V, et al. The brainstem locus coeruleus and migraine. 18^th European Headache Congress, 4–7 December 2024, Rotterdam, the Netherlands.

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Posted on 6 January 20256 January 2025