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Divergent influences of the locus coeruleus on migraine pathophysiology

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)385-394
JournalPain
Volume160
Issue number2
Early online date26 Oct 2018
DOIs
Publication statusE-pub ahead of print - 26 Oct 2018

King's Authors

Abstract

Migraine is a common disabling neurological condition that is associated with several premonitory symptoms that can occur days before the headache onset. The most commonly reported premonitory symptom is abnormal fatigue that has been shown to be highly predictive of an ensuing migraine attack.
The locus coeruleus (LC) is a key nucleus involved in arousal that has also been shown to impact pain processing. It provides one of the major sources of noradrenaline to the dorsal horn of the spinal cord and neocortex. Given the clinical association between migraine, sleep-wake regulation and fatigue we sought to determine if LC modulation could impact migraine-related phenotypes in several validated preclinical models of migraine. To determine its role in migraine-related pain we recorded dural nociceptive-evoked responses in the trigeminocervical complex that receives trigeminal primary afferents from the durovasculature. Additionally, we explored the susceptibility to cortical spreading depression initiation, the presumed underlying phenomenon leading to migraine aura.
Our experiments reveal a potent role for LC disruption in the differential modulation of migraine-related phenotypes, inhibiting dural-evoked activation of wide dynamic neurons in the trigeminocervical complex whilst increasing cortical spreading depression susceptibility. This highlights the potential divergent impact of LC disruption in migraine physiology that may help explain the complex interactions between dysfunctional arousal mechanisms and migraine.

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