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Papers of the Week

2022 Aug-Dec

Neurobiol Pain


Stimulation of CGRP-expressing neurons in the medial cerebellar nucleus induces light and touch sensitivity in mice.


Wang M, Castonguay WC, Duong TL, Huebner MW, Flinn HC, Greenway AM, Russo AF, Sowers LP
Neurobiol Pain. 2022 Aug-Dec; 12:100098.
PMID: 35782531.


Calcitonin gene-related peptide (CGRP) is considered a major player in migraine pathophysiology. However, the location and mechanisms of CGRP actions in migraine are not clearly elucidated. One important question yet to be answered is: Does central CGRP signaling play a role in migraine? One candidate site is the cerebellum, which serves as a sensory and motor integration center and is activated in migraine patients. The cerebellum has the most CGRP binding sites in the central nervous system and a deep cerebellar nucleus, the medial nucleus (MN), expresses CGRP (MN). A previous study demonstrated that CGRP delivery into the cerebellum induced migraine-like behaviors. We hypothesized that stimulation of MN neurons might induce migraine-like behaviors. To test the hypothesis, we used an optogenetic strategy using mice to drive Cre-dependent expression of channelrhodopsin-2 selectively in CGRP neurons in the cerebellar MN. A battery of behavioral tests was done to assess preclinical behaviors that are surrogates of migraine symptoms, including light aversion, cutaneous allodynia, and spontaneous pain when MN neurons were optically stimulated. Motor functions were also assessed. Optical stimulation of MN neurons decreased the time spent in the light, which was coupled to increased time spent resting in the dark, but not the light. These changes were only significant in female mice. Plantar tactile sensitivity was increased in the ipsilateral paws of both sexes, but contralateral paw data were less clear. There was no significant increase in anxiety-like behavior, spontaneous pain (squint), or changes in gait. These discoveries reveal that MN neurons may contribute to migraine-like sensory hypersensitivity to light and touch.