Controlled activation of cortical astrocytes can reverse neuropathic chronic pain

Abstract Chronic pain is a major public health problem that currently lacks effective treatment options. Here, we report a novel combination therapy that can effectively reverse chronic pain induced by nerve injury in mice. By combing transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with transient concurrent activation of astrocytes in the somatosensory cortex (S1) by either transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia previously established by partial sciatic nerve ligation (PSL). Activation of astrocytes initiated spine plasticity to reduce synapses formed shortly after PSL. The cure from allodynia persisted long after ceasing active treatment. Thus, our study represents the first report of a robust, readily translatable approach for treating chronic pain that capitalizes on the causative interplay between noxious afferents, sensitized central neuronal circuits and astrocytic-activation induced plasticity.