Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour

Ikuko Takeda, Kohei Yoshihara, Dennis L. Cheung, Tomoko Kobayashi, Masakazu Agetsuma, Makoto Tsuda, Kei Eto, Schuichi Koizumi, Hiroaki Wake, Andrew J. Moorhouse and Junichi Nabekura ()
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Ikuko Takeda: National Institute for Physiological Sciences
Kohei Yoshihara: Kyushu University
Dennis L. Cheung: National Institute for Physiological Sciences
Tomoko Kobayashi: National Institute for Physiological Sciences
Masakazu Agetsuma: National Institute for Physiological Sciences
Makoto Tsuda: Kyushu University
Kei Eto: National Institute for Physiological Sciences
Schuichi Koizumi: University of Yamanashi
Hiroaki Wake: Nagoya University
Andrew J. Moorhouse: The University of New South Wales
Junichi Nabekura: National Institute for Physiological Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Chronic pain is a major public health problem that currently lacks effective treatment options. Here, a method that can modulate chronic pain-like behaviour induced by nerve injury in mice is described. By combining a transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with concurrent activation of astrocytes in the somatosensory cortex (S1) by either low intensity transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia-like behaviour previously established by partial sciatic nerve ligation (PSL). Such activation of astrocytes initiated spine plasticity to reduce those synapses formed shortly after PSL. This reversal from allodynia-like behaviour persisted well beyond the active treatment period. Thus, our study demonstrates a robust and potentially translational approach for modulating pain, that capitalizes on the interplay between noxious afferents, sensitized central neuronal circuits, and astrocyte-activation induced synaptic plasticity.

Date: 2022
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DOI: 10.1038/s41467-022-31773-8

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