# Astrocytogenic bidirectional plasticity at spinal nociceptive synapses regulates acute nociceptive processing

**Authors:** Sibel Ada, Laura Klinger, Hannah L. Teuchmann, Valeria Mussetto, Viktoria Hadschieff, Mira T. Kronschläger, Anna S.M. Siegert, Lidia Trofimova, Raphael Holzinger, Danijela Kurija, Ruth Drdla-Schutting

PMC · DOI: 10.1097/j.pain.0000000000003805 · Pain · 2025-09-03

## TL;DR

Astrocytes actively regulate spinal pain signals in real time, either reducing or increasing pain transmission based on current conditions.

## Contribution

Astrocytes are shown to dynamically regulate acute nociception through bidirectional plasticity at spinal synapses.

## Key findings

- Astrocytes can suppress nociceptive transmission by enhancing glycinergic tone.
- Astrocytes can amplify synaptic strength at C-fiber synapses via interactions with microglia.
- Astrocytes dynamically regulate spinal nociceptive networks to shape pain perception in real time.

## Abstract

Supplemental Digital Content is Available in the Text.

Astrocytes are key players in chronic pain, driving maladaptive changes in neuronal circuits. Yet, their influence on acute nociception—the body's first line of defense against harmful stimuli—remains poorly understood. Using chemogenetic tools to mimic endogenous astrocytic G-protein–coupled receptor-mediated signaling, we reveal that astrocytes induce bidirectional plasticity at nociceptive synapses in the dorsal horn. Depending on the state of these synapses and on concurrent afferent input, astrocytes can either suppress nociceptive transmission by enhancing glycinergic tone, or amplify synaptic strength at C-fiber synapses through interactions with microglia. This dynamic regulation expands the acute computational capacity of spinal nociceptive networks, enabling precise and adaptive responses to noxious stimuli on a short time scale. Our findings challenge the traditional view of astrocytes as passive supporters of neuronal activity and establish them as active regulators of spinal plasticity, integrating sensory information and network states to shape pain perception in real time.

## Full-text entities

- **Diseases:** nociceptive (MESH:D059226), pain (MESH:D010146), chronic pain (MESH:D059350)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12794346/full.md

## References

84 references — full list in the complete paper: https://tomesphere.com/paper/PMC12794346/full.md

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Source: https://tomesphere.com/paper/PMC12794346