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What do we already know about this topic?

  • Previous studies suggest calcitonin gene-related peptide (CGRP) plays a critical role in migraine pathophysiology, but the location and mechanisms of CGRP in migraine are still unknown.
  • A high number of CGRP binding sites are located in the cerebellum, which serves as a sensory and motor integrative center, and is activated during a migraine attack.1
  • CGRP is densely distributed in the Purkinje cells (PCs) and cerebellum medial nucleus, suggesting that CGRP may act on the cerebellum to induce migraine-like behaviors.

How was this study conducted?

  • CGRP expression was measured in the cerebellum of C57BL/6 mice using qPCR and immunohistochemistry, and in calca-cre mice using a cre-dependent viral reporter (AAV-EF1a-DIO-EYFP).
  • The mice were injected with CGRP into the cerebellar vermis V and fastigial nucleus and tested in the light-dark assay to evaluate light aversion.
  • An open field test was used to evaluate anxiety and locomotion, sensitivity to plantar Von Frey filaments, and a squint test was used to evaluate pain.
  • A cerebellar CGRP sensitized mouse model (L7/hRAMP1) was created to further test the role of cerebellar CGRP in migraine.
  • Rats were injected with CGRP into crus I in the cerebellar cortex and were run in an interval estimation task.