Publications by authors named "Thomas L Duong"

2 Publications

  • Page 1 of 1

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

Neurobiol Pain 2022 Aug-Dec;12:100098. Epub 2022 Jun 23.

Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.

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.
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http://dx.doi.org/10.1016/j.ynpai.2022.100098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240374PMC
June 2022

CGRP Administration Into the Cerebellum Evokes Light Aversion, Tactile Hypersensitivity, and Nociceptive Squint in Mice.

Front Pain Res (Lausanne) 2022 25;3:861598. Epub 2022 Apr 25.

Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States.

The neuropeptide calcitonin gene-related peptide (CGRP) is a major player in migraine pathophysiology. Previous preclinical studies demonstrated that intracerebroventricular administration of CGRP caused migraine-like behaviors in mice, but the sites of action in the brain remain unidentified. The cerebellum has the most CGRP binding sites in the central nervous system and is increasingly recognized as both a sensory and motor integration center. The objective of this study was to test whether the cerebellum, particularly the medial cerebellar nuclei (MN), might be a site of CGRP action. In this study, CGRP was directly injected into the right MN of C57BL/6J mice via a cannula. A battery of tests was done to assess preclinical behaviors that are surrogates of migraine-like symptoms. CGRP caused light aversion measured as decreased time in the light zone even with dim light. The mice also spent more time resting in the dark zone, but not the light, along with decreased rearing and transitions between zones. These behaviors were similar for both sexes. Moreover, significant responses to CGRP were seen in the open field assay, von Frey test, and automated squint assay, indicating anxiety, tactile hypersensitivity, and spontaneous pain, respectively. Interestingly, CGRP injection caused significant anxiety and spontaneous pain responses only in female mice, and a more robust tactile hypersensitivity in female mice. No detectable effect of CGRP on gait was observed in either sex. These results suggest that CGRP injection in the MN causes light aversion accompanied by increased anxiety, tactile hypersensitivity, and spontaneous pain. A caveat is that we cannot exclude contributions from other cerebellar regions in addition to the MN due to diffusion of the injected peptide. These results reveal the cerebellum as a new site of CGRP actions that may contribute to migraine-like hypersensitivity.
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http://dx.doi.org/10.3389/fpain.2022.861598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082264PMC
April 2022
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