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Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour

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. Astrocytes may contribute to synaptic remodelling in the cortex in chronic pain states. Here the authors describe modulation of astrocyte activity to drive circuit reorganization in somatosensory cortex in mice, along with peripheral nerve block, which could be a potential therapeutic approach for the treatment of chronic pain.

SUBMITTER: Takeda I

PROVIDER: S-EPMC9283422 | biostudies-literature |

REPOSITORIES: biostudies-literature

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