Low 5-HT 1B receptor binding in the migraine brain: A PET study

Cephalalgia. 2018 Mar;38(3):519-527. doi: 10.1177/0333102417698708. Epub 2017 Mar 15.

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.

Keywords: Headache; neuroimaging; pain modulation; raphe; serotonin; serotonin 1B receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Migraine Disorders / diagnostic imaging
  • Migraine Disorders / metabolism*
  • Positron-Emission Tomography
  • Radioligand Assay
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT1B / metabolism*

Substances

  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT1B