TY - JOUR

T1 - Low 5-HT1B receptor binding in the migraine brain

T2 - A PET study

AU - Deen, Marie

AU - Hansen, Hanne D

AU - Hougaard, Anders

AU - da Cunha-Bang, Sofi

AU - Nørgaard, Martin

AU - Svarer, Claus

AU - Keller, Sune H

AU - Thomsen, Carsten

AU - Ashina, Messoud

AU - Knudsen, Gitte M

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Adult

KW - Brain/diagnostic imaging

KW - Female

KW - Humans

KW - Image Interpretation, Computer-Assisted

KW - Magnetic Resonance Imaging

KW - Male

KW - Migraine Disorders/diagnostic imaging

KW - Positron-Emission Tomography

KW - Radioligand Assay

KW - Radiopharmaceuticals

KW - Receptor, Serotonin, 5-HT1B/metabolism

U2 - 10.1177/0333102417698708

DO - 10.1177/0333102417698708

M3 - Journal article

C2 - 28730894

VL - 38

SP - 519

EP - 527

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 3

ER -