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Structural and Functional Properties of Spinal Dorsal Horn Neurons After Peripheral Nerve Injury Change Overtime Via Astrocyte Activation

Overview
Journal iScience
Publisher Cell Press
Date 2022 Nov 29
PMID 36444301
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Abstract

Chronic pain remains challenging to treat, despite numerous reports of its pathogenesis, including neuronal plasticity in the spinal dorsal horn (SDH). We hypothesized that understanding plasticity only at a specific time point after peripheral nerve injury (PNI) is insufficient to solve chronic pain. Here, we analyzed the temporal changes in synaptic transmission and astrocyte-neuron interactions in SDH after PNI. We found that synaptic transmission in the SDH after PNI changed in a time-dependent manner, which was accompanied by astrocyte proliferation and loss of inhibitory and excitatory neurons. Furthermore, neuronal loss was accompanied by necroptosis. Short-term inhibition of astrocytes after PNI suppressed these physiological and morphological changes and long-term pain-related behaviors. These results are the first to demonstrate that the inhibition of astrocyte proliferation after PNI contributes to the long-term regulation of plasticity and of necroptosis development in the SDH.

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