Purkinje cells of vestibulocerebellum play an important role in acute vestibular migraine

Gu, Hongbin; Xu, Jin; Zhang, Zhaohuan; Li, Fēi; Feng, Meiyan; Tian, Qing; Shang, Chen-Yong; Zhuang, Jianhua

doi:10.31083/j.jin.2019.04.1168

Cited by 15 publications

(11 citation statements)

References 51 publications

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“…There is also evidence of otolithic pathway abnormalities in individuals with VM [34]. It is also suggested that Purkinje cells in the paraflocculus could be inhibited after the occurrence of a migraine episode, which may be an important factor leading to vestibular migraine [35]. Magnetic resonance studies have shown an increased thalamic activation in VM patients during vestibular stimulation compared to healthy controls, as well as grey matter volume abnormalities of nociceptive and multisensory vestibular brain areas [36,37].…”

Section: Pathophysiology Of Vmmentioning

confidence: 99%

Vestibular migraine — an underdiagnosed cause of vertigo. Diagnosis and treatment

Nowaczewska

2020

Neurol Neurochir Pol.

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Introduction. Migraine and vertigo are two common conditions. The main disorder connecting both these entities is vestibular migraine (VM). State of the art. VM may affect 1-3% of the general population. It is a disabling disease of recurrent attacks of vestibular symptoms accompanied by migraine features which occur in patients with a current or previous history of migraine. The episodes can last minutes, hours or even days, and may occur without any concurrent headache, which can prompt misdiagnosis. VM often begins several years after a typical migraine, and the delay between onset of headache and vertigo may be long. The diagnosis is based on the patient's clinical history and can be challenging due to the lack of an established confirmatory diagnostic test or biomarkers. The mechanism of vestibular migraine remains unclear and is still under investigation, but it seems to be an interaction between trigeminal and vestibular systems. Due to the lack of specific trials, treatment recommendations are based on migraine guidelines. Several drugs seem to be effective, although there have been few randomised controlled trials in this area. Regardless of the published strict and detailed diagnostic criteria, this condition remains little known, and as a consequence is underdiagnosed and undertreated. Clinical implications. Efforts should be made to educate medical communities and patients about this disease and to encourage neurologists and ENT specialists to cooperate. Every patient with vertigo of unknown origin should be directly asked about a past or present history of migraine, or migraine symptoms experienced during their vertigo episodes. Future directions. There is a growing need for studies regarding the pathophysiology of VM as well as randomised trials to establish clear treatment recommendations and to improve management of this surprisingly common disorder.

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Section: Pathophysiology Of Vmmentioning

confidence: 99%

Vestibular migraine — an underdiagnosed cause of vertigo. Diagnosis and treatment

Nowaczewska

2020

Neurol Neurochir Pol.

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“…Brain imaging studies have reported that the cerebellar sodium concentration and functional connectivity to the insula or anterior cingulate cortex were altered in animal migraine models induced by nitroglycerin or inflammatory soup ( 53 – 55 ). The firing rate of Purkinje cells in the rat paraflocculus was decreased in an animal model induced by trigeminal stimulation ( 56 ), and the organization of parallel fibers to Purkinje cell synapses was abnormal in familial hemiplegic migraine type 1 mouse models ( 57 , 58 ). There are also preclinical behavioral studies investigating the role of the cerebellum in pain modulation ( 41 – 43 , 59 – 64 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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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“…To our knowledge, this is the first preclinical cerebellar migraine study looking at behavioral outcomes. Indeed, there have been few animal studies looking at imaging and electrophysiological links between the cerebellum and migraine (87)(88)(89)(90)(91)(92). Brain imaging studies have reported that the cerebellar sodium concentration and functional connectivity to the insula or anterior cingulate cortex were altered in animal migraine models induced by nitroglycerin or inflammatory soup (87)(88)(89).…”

Section: Discussionmentioning

confidence: 99%

“…Brain imaging studies have reported that the cerebellar sodium concentration and functional connectivity to the insula or anterior cingulate cortex were altered in animal migraine models induced by nitroglycerin or inflammatory soup (87)(88)(89). The firing rate of Purkinje cells in the rat paraflocculus was decreased in an animal model induced by trigeminal stimulation (90), and the organization of parallel fibers to Purkinje cell synapses was abnormal in familial hemiplegic migraine type 1 mouse models (91,92). There are also preclinical behavioral studies investigating the role of the cerebellum in pain modulation (70)(71)(72)(93)(94)(95)(96)(97)(98)(99).…”

Section: Discussionmentioning

confidence: 99%

CGRP Administration into the Cerebellum Evokes Migraine-like Behaviors Predominately in Female Mice

Duong

Rea

Waite

et al. 2022

Preprint

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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 behavioral tests was done to assess migraine-like behaviors. 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. In contrast, significant responses to CGRP were seen only with female mice in the open field assay, von Frey test, and automated squint assay, indicating anxiety, tactile hypersensitivity, and spontaneous pain, respectively. In male mice, the responses had the same trend as females but did not reach statistical significance. No detectable effect of CGRP on gait was observed in either sex. These results suggest that CGRP in the MN causes light aversion in males, while in females, light aversion is 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 pathophysiology and possibly its prevalence in females.

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Purkinje cells of vestibulocerebellum play an important role in acute vestibular migraine

Abstract: J o u r n a l o f I n t e g r a t i v e N e u r o s c i e n c e

Cited by 15 publications

References 51 publications

Vestibular migraine — an underdiagnosed cause of vertigo. Diagnosis and treatment

Vestibular migraine — an underdiagnosed cause of vertigo. Diagnosis and treatment

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

CGRP Administration into the Cerebellum Evokes Migraine-like Behaviors Predominately in Female Mice

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