Trehalose Reduces Nerve Injury Induced Nociception in Mice but Negatively Affects Alertness

Kraft, Vanessa A N; Schmitz, Katja; Wilken-Schmitz, Annett; Geißlinger, Gerd; Sisignano, Marco; Tegeder, Irmgard

doi:10.3390/nu13092953

Cited by 5 publications

(4 citation statements)

References 66 publications

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“…Nociceptive and motor tests were performed at 8–12 weeks of age (n = 12 and 14) and 40–43 weeks of age (n = 15 and n = 16 for ChR2-flfl and Avil-ChR2) as described [ 50 – 53 ].…”

Section: Methodsmentioning

confidence: 99%

Repetitive and compulsive behavior after Early-Life-Pain associated with reduced long-chain sphingolipid species

Vogel,

Ueberbach,

Wilken-Schmitz

et al. 2023

Cell Biosci

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Background Pain in early life may impact on development and risk of chronic pain. We developed an optogenetic Cre/loxP mouse model of “early-life-pain” (ELP) using mice with transgenic expression of channelrhodopsin-2 (ChR2) under control of the Advillin (Avil) promoter, which drives expression of transgenes predominantly in isolectin B4 positive non-peptidergic nociceptors in postnatal mice. Avil-ChR2 (Cre +) and ChR2-flfl control mice were exposed to blue light in a chamber once daily from P1-P5 together with their Cre-negative mother. Results ELP caused cortical hyperexcitability at P8-9 as assessed via multi-electrode array recordings that coincided with reduced expression of synaptic genes (RNAseq) including Grin2b, neurexins, piccolo and voltage gated calcium and sodium channels. Young adult (8–16 wks) Avil-ChR2 mice presented with nociceptive hypersensitivity upon heat or mechanical stimulation, which did not resolve up until one year of age. The persistent hypersensitivy to nociceptive stimuli was reflected by increased calcium fluxes in primary sensory neurons of aged mice (1 year) upon capsaicin stimulation. Avil-ChR2 mice behaved like controls in maze tests of anxiety, social interaction, and spatial memory but IntelliCage behavioral studies revealed repetitive nosepokes and corner visits and compulsive lickings. Compulsiveness at the behavioral level was associated with a reduction of sphingomyelin species in brain and plasma lipidomic studies. Behavioral studies were done with female mice. Conclusion The results suggest that ELP may predispose to chronic “pain” and compulsive psychopathology in part mediated by alterations of sphingolipid metabolism, which have been previously described in the context of addiction and psychiatric diseases. Graphical Abstract

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“…Nociceptive and motor tests were performed at 8–12 weeks of age (n = 12 and 14) and 40–43 weeks of age (n = 15 and n = 16 for ChR2-flfl and Avil-ChR2) as described [ 50 – 53 ].…”

Section: Methodsmentioning

confidence: 99%

Repetitive and compulsive behavior after Early-Life-Pain associated with reduced long-chain sphingolipid species

Vogel,

Ueberbach,

Wilken-Schmitz

et al. 2023

Cell Biosci

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“…Nociceptive and motor tests were performed at 8-12 weeks of age (n = 12 and 14) and 40-43 weeks of age (n = 15 and n = 16 for ChR2and Avil-ChR2) as described [47][48][49][50].…”

Section: Assessment Of Nociception and Motor Functionmentioning

confidence: 99%

Repetitive and compulsive behavior after Early-Life-Pain in mice

Vogel

Ueberbach

Wilken-Schmitz

et al. 2023

Preprint

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Pain in early life may affect cortical development and risk of chronic pain. We developed an optogenetic Cre/loxP mouse model of "early-life-pain" (ELP) using mice with transgenic expression of channelrhodopsin-2 (ChR2) under control of the Advillin (Avil) promoter, which drives expression of ChR2 in peripheral somatosensory neurons. Avil-ChR2 (Cre+) and ChR2-flfl control mice were exposed to blue light in a chamber once daily from P1-P5 together with their Cre-negative mother. ELP caused cortical hyperexcitability at P8-9 as assessed via multi-electrode array recordings that coincided with reduced expression of synaptic genes (RNAseq) including Grin2b, neurexins, piccolo and voltage gated calcium and sodium channels, suggesting activity-dependent synaptic pruning. Young adult (8-16 wks) Avil-ChR2 mice presented with nociceptive hypersensitivity upon heat or mechanical stimulation, which did not resolve up until one year of age. The persistent "pain" phenotype was reflected by capsaicin hypersensitivity in primary sensory neurons of aged mice (1 year) as assessed by calcium imaging. Adult Avil-ChR2 mice behaved like controls in maze tests of anxiety, social interaction and spatial memory but IntelliCage behavioral studies revealed repetitive nosepokes and corner visits and compulsive lickings. Compulsiveness at the behavioral level was associated with a reduction of sphingomyelin species in brain and plasma lipidomic studies pointing to alterations of sphingolipid metabolisms, which have been previously described in the context of addiction and psychiatric diseases. Hence, ELP may predispose to chronic pain and compulsive psychopathology.

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“…Nociceptive and motor tests were performed at 8-12 weeks of age (n = 12 and 14) and 40-43 weeks of age (n = 15 and n = 16 for ChR2-and Avil-ChR2) as described [41][42][43][44] .…”

Section: Assessment Of Nociception and Motor Functionmentioning

confidence: 99%

Optogenetic Early Life Pain leads to cortical hyperexcitability, nociceptive hypersensitivity and repetitive behavior

Tegeder

Vogel

Ueberbach

et al. 2022

Preprint

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Pain in early life may affect cortical development and risk of chronic pain. We developed an optogenetic Cre/loxP mouse model of "early-life-pain" (ELP) using mice with transgenic expression of channelrhodopsin-2 (ChR2) under control of the Advillin (Avil) promoter, that drives expression of ChR2 in peripheral somatosensory neurons. Avil-ChR2 (Cre+) and ChR2-flfl control mice were exposed to blue light in a chamber once daily from P1-P5 together with their Cre-negative mother. ELP caused cortical hyperexcitability at P8-9 as assessed via multi-electrode array recordings that coincided with reduced expression of synaptic genes (RNAseq) including Grin2b, neurexins, piccolo and voltage gated calcium and sodium channels which would agree with activity-dependent synaptic pruning. Young adult Avil-ChR2 mice presented with nociceptive hypersensitivity upon heat or mechanical stimulation, which did not resolve up until one year of age. The persistent "pain" phenotype was reflected by capsaicin hypersensitivity in primary sensory neurons of aged mice as assessed by calcium imaging. Avil-ChR2 mice had no disadvantages in Maze tests of anxiety, social interaction and spatial memory, and multiple dimensions of cognitive behavior in IntelliCages. But they stood out by a high rate of repetitive nosepokes, and repetitive corner returns irrespective of success, suggesting inflexibility. Hence, optogenetic early life pain leads to pain in adult mice and repetitive behavior but without cognitive or social deficits.

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Trehalose Reduces Nerve Injury Induced Nociception in Mice but Negatively Affects Alertness

Cited by 5 publications

References 66 publications

Repetitive and compulsive behavior after Early-Life-Pain associated with reduced long-chain sphingolipid species

Repetitive and compulsive behavior after Early-Life-Pain associated with reduced long-chain sphingolipid species

Repetitive and compulsive behavior after Early-Life-Pain in mice

Optogenetic Early Life Pain leads to cortical hyperexcitability, nociceptive hypersensitivity and repetitive behavior

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