CGRP Administration Into the Cerebellum Evokes Light Aversion, Tactile Hypersensitivity, and Nociceptive Squint in Mice.
CGRP Administration Into the Cerebellum Evokes Light Aversion, Tactile Hypersensitivity, and Nociceptive Squint in Mice.
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DOI：
10.3389/fpain.2022.861598
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发表时间：
2022
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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神经肽降钙素基因相关肽（CGRP）是偏头痛病理生理学的主要参与者。先前的临床前研究表明，侧脑室注射CGRP可导致小鼠出现偏头痛样行为，但其在大脑中的作用部位仍未确定。小脑在中枢神经系统中具有最多的CGRP结合位点，并且越来越多地被认为是感觉和运动整合中心。本研究的目的是测试是否小脑，特别是小脑内侧核（MN），可能是CGRP的行动的网站。本研究通过插管将CGRP直接注射到C57BL/6J小鼠的右侧MN中。进行了一系列测试，以评估作为偏头痛样症状替代物的临床前行为。CGRP引起光厌恶，测量为即使在昏暗的光下在光区中的时间减少。小鼠在黑暗区域休息的时间也更长，但在明亮区域休息的时间却不长，沿着的是直立和区域之间的转换减少。这些行为对两性来说是相似的。此外，在旷场试验、von Frey试验和自动斜视试验中观察到对CGRP的显著反应，分别表明焦虑、触觉超敏反应和自发性疼痛。有趣的是，CGRP注射仅在雌性小鼠中引起显著的焦虑和自发性疼痛反应，并且在雌性小鼠中引起更强烈的触觉超敏反应。在两种性别中均未观察到CGRP对步态的可检测影响。这些结果表明，CGRP注射在MN引起光厌恶伴随着增加的焦虑，触觉过敏，和自发性疼痛。需要注意的是，由于注射肽的扩散，我们不能排除除了MN之外的其他小脑区域的贡献。这些结果揭示了小脑作为CGRP作用的新位点，可能有助于偏头痛样超敏反应。
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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影响因子：
12.8
作者：
Babaev O;Piletti Chatain C;Krueger-Burg D
通讯作者：
Krueger-Burg D
影响因子：
7.4
作者：
Abad N;Rosenberg JT;Hike DC;Harrington MG;Grant SC
通讯作者：
Grant SC
影响因子：
3.5
作者：
Baumann, Oliver;Borra, Ronald J.;Bower, James M.;Cullen, Kathleen E.;Habas, Christophe;Ivry, Richard B.;Leggio, Maria;Mattingley, Jason B.;Molinari, Marco;Moulton, Eric A.;Paulin, Michael G.;Pavlova, Marina A.;Schmahmann, Jeremy D.;Sokolov, Arseny A.
通讯作者：
Sokolov, Arseny A.
DOI：
10.1073/pnas.1009500107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Adams, Paul J.;Rungta, Ravi L.;Snutch, Terrance P.
通讯作者：
Snutch, Terrance P.
影响因子：
2.5
作者：
HAYASHI, H;SUMINO, R;SESSLE, BJ
通讯作者：
SESSLE, BJ