Low 5-HT1B receptor binding in the migraine brain: A PET study

Marie Deen, Hanne D Hansen, Anders Hougaard, Sofi da Cunha-Bang, Martin Nørgaard, Claus Svarer, Sune H Keller, Carsten Thomsen, Messoud Ashina, Gitte M Knudsen

15 Citationer (Scopus)

Abstract

Background: The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim: To examine the cerebral 5-HT1B receptor binding in interictal migraine patients without aura compared to controls. Methods: Eighteen migraine patients, who had been migraine free for >48 hours, and 16 controls were scanned after injection of the 5-HT1B receptor specific radioligand [11C]AZ10419369 for quantification of cerebral 5-HT1B receptor binding. Patients who reported migraine <48 hours after the PET examination were excluded from the final analysis. We defined seven brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results: Our data support a model wherein group status predicts the latent variable (p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor binding in the dorsal raphe and in the midbrain. Conclusion: We report here for the first time that migraine patients have low 5-HT1B receptor binding in pain modulating regions, reflecting decreased receptor density. This is either a primary constitutive trait of the migraine brain or secondary to repeated exposure to migraine attacks. We also provide indirect support for the dorsal raphe 5-HT1B receptors being temporarily downregulated during the migraine attack, presumably in response to higher cerebral serotonin levels in the ictal phase.

OriginalsprogEngelsk
TidsskriftCephalalgia : an international journal of headache
Vol/bind38
Udgave nummer3
Sider (fra-til)519-527
Antal sider9
ISSN0333-1024
DOI
StatusUdgivet - 1 mar. 2018

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