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Exploring the role of spinal astrocytes in the onset of hyperalgesic priming signals in acid-induced chronic muscle pain.

ABSTRACT: Hyperalgesic priming, a form of pain plasticity initiated by initial injury, leads to heightened sensitivity to subsequent noxious stimuli, contributing to chronic pain development in animals. While astrocytes play active roles in modulating synaptic transmission in various pain models, their specific involvement in hyperalgesic priming remains elusive. Here, we show that spinal astrocytes are essential for hyperalgesic priming formation in a mouse model of acid-induced muscle pain. We observed spinal astrocyte activation 4 h after initial acid injection, and inhibition of this activation prevented chronic pain development upon subsequent acid injection. Chemogenetic activation of spinal astrocytes mimicked the first acid-induced hyperalgesic priming. We also demonstrated that spinal phosphorylated extracellular regulated kinase (pERK)-positive neurons were mainly vesicular glutamate transporter-2 positive (Vglut2⁺) neurons after the first acid injection, and inhibition of spinal pERK prevented astrocyte activation. Furthermore, pharmacological inhibition of astrocytic glutamate transporters glutamate transporter-1 and glutamate-aspartate transporter abolished the hyperalgesic priming. Collectively, our results suggest that pERK activation in Vglut2⁺ neurons activate astrocytes through astrocytic glutamate transporters. This process eventually establishes hyperalgesic priming through spinal D-serine. We conclude that spinal astrocytes play a crucial role in the transition from acute to chronic pain.

SUBMITTER: Abdelaziz MA

PROVIDER: S-EPMC11370897 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Exploring the role of spinal astrocytes in the onset of hyperalgesic priming signals in acid-induced chronic muscle pain.

Abdelaziz Mohamed Abbas MA Chen Wei-Hsin WH Chang Yu-Wang YW Mindaye Selomon Assefa SA Chen Chien-Chang CC

PNAS nexus 20240830 9

Hyperalgesic priming, a form of pain plasticity initiated by initial injury, leads to heightened sensitivity to subsequent noxious stimuli, contributing to chronic pain development in animals. While astrocytes play active roles in modulating synaptic transmission in various pain models, their specific involvement in hyperalgesic priming remains elusive. Here, we show that spinal astrocytes are essential for hyperalgesic priming formation in a mouse model of acid-induced muscle pain. We observed ...[more]

PMID: 39228816

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Dataset Information

Exploring the role of spinal astrocytes in the onset of hyperalgesic priming signals in acid-induced chronic muscle pain.

Publications

Exploring the role of spinal astrocytes in the onset of hyperalgesic priming signals in acid-induced chronic muscle pain.

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