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. 2025 Sep 3.
doi: 10.1097/j.pain.0000000000003805. Online ahead of print.

Astrocytogenic bidirectional plasticity at spinal nociceptive synapses regulates acute nociceptive processing

Sibel Ada  1 , 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
Affiliations

Astrocytogenic bidirectional plasticity at spinal nociceptive synapses regulates acute nociceptive processing

Sibel Ada et al. Pain. .

Abstract

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.

Keywords: Acute nociception; Astrocyte; Gq-DREADDs; Plasticity; Spinal cord.

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References

    1. Agulhon C, Petravicz J, McMullen AB, Sweger EJ, Minton SK, Taves SR, Casper KB, Fiacco TA, McCarthy KD. What is the role of astrocyte calcium in Neurophysiology? Neuron 2008;59:932–46.
    1. Bai H-H, Liu J-P, Yang L, Zhao J-Y, Suo Z-W, Yang X, Hu X-D. Adenosine A1 receptor potentiated glycinergic transmission in spinal cord dorsal horn of rats after peripheral inflammation. Neuropharmacology 2017;126:158–67.
    1. Bazargani N, Attwell D. Astrocyte calcium signaling: the third wave. Nat Neurosci 2016;19:182–9.
    1. Bonin RP, Bories C, De Koninck Y. A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments. Mol Pain 2014;10:26.
    1. Bossuyt J, Van Den Herrewegen Y, Nestor L, Buckinx A, De Bundel D, Smolders I. Chemogenetic modulation of astrocytes and microglia: state-of-the-art and implications in neuroscience. Glia 2023;71:2071–95.

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