Prevalence and characteristics of cutaneous allodynia in probable migraine

Han, Seung Min; Kim, Kyung Min; Cho, Soo-Jin; Yang, Kwang Ik; Kim, Dae-Young; Yun, Chang Ho; Chu, Min Kyung

doi:10.1038/s41598-021-82080-z

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…Furthermore, repeated NTG exposure causes a chronic hypersensitivity that lasts several weeks in murine models 6 . This chronic hypersensitivity is characterized by generalized cutaneous sensitization, which has also been described as a reliable predictor of migraine chronification in humans 7 , 8 that is found more prevalently in women 9 , 10 .…”

Section: Introductionmentioning

confidence: 94%

TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

et al. 2022

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TRPA1 and TRPM8 are transient receptor potential channels expressed in trigeminal neurons that are related to pathophysiology in migraine models. Here we use a mouse model of nitroglycerine-induced chronic migraine that displays a sexually dimorphic phenotype, characterized by mechanical hypersensitivity that develops in males and females, and is persistent up to day 20 in female mice, but disappears by day 18 in male mice. TRPA1 is required for development of hypersensitivity in males and females, whereas TRPM8 contributes to the faster recovery from hypersensitivity in males. TRPM8-mediated antinociception effects required the presence of endogenous testosterone in males. Administration of exogenous testosterone to females and orchidectomized males led to recovery from hypersensitivity. Calcium imaging and electrophysiological recordings in in vitro systems confirmed testosterone activity on murine and human TRPM8, independent of androgen receptor expression. Our findings suggest a protective function of TRPM8 in shortening the time frame of hypersensitivity in a mouse model of migraine.

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Section: Introductionmentioning

confidence: 94%

TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

et al. 2022

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“…The prevalence of CA in migraine is highly variable (8,43) in the literature (Table 1), although it can be considered that between 40 and 70% of the patients with migraine experience this symptom, according to population-based studies (26,36,37). Several factors influence these differences including the heterogeneity of the populations in each study (populationbased nationwide studies, cross-sectional studies or prospective case series) and the methodology used for the identification of CA .…”

Section: Epidemiology Of Allodynia In Migrainementioning

confidence: 99%

Cutaneous Allodynia in Migraine: A Narrative Review

et al. 2022

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ObjectiveIn the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine.BackgroundCA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view.MethodsWe performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search.ResultsThe prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications.ConclusionsCA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.

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“…Given that we also observed anxiety behavior primarily in female mice, it is interesting that allodynia is associated with a higher risk for anxiety and a correlation exists between their severity in migraine patients ( 80 ). Anxiety was more prevalent in patients with migraine and probable migraine with cutaneous allodynia than those without cutaneous allodynia ( 81 ). In animal models, stress elicited higher pain sensitivity ( 82 ).…”

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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Prevalence and characteristics of cutaneous allodynia in probable migraine

Cited by 13 publications

References 48 publications

TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

Cutaneous Allodynia in Migraine: A Narrative Review

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

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