Sustained Neuronal Stimulation Activates Paraventricular Thalamus Astrocytes for Chronicity of Neuropathic Pain in Mice

Current treatments for chronic neuropathic pain are limited in efficacy, partly due to the complicated etiology of neuropathic pain chronicity. Ongoing nociceptive inputs from peripheral injuries lead to maladaptive alterations in the central nervous system during the transition from acute to chronic pain, which in turn contribute to the maintenance of chronic pain and reduce the effectiveness of peripheral analgesics. Reactive astrocytes are known to contribute to chronic neuropathic pain in the spinal cord, while how astrocytes contribute to chronic pain in supraspinal nuclei remains unclear. This study reveals that continuous painful stimulation from peripheral injury induces astrocyte reactivity and downregulation of astrocytic Kir4.1 (inward rectifying potassium channel protein 4.1) in the paraventricular thalamus (PVT). In turn, these reactive astrocytes help to maintain neuronal hyperactivity in the PVT and enhance neural projections from PVT to the medial prefrontal cortex (mPFC), which contribute to hyperalgesia in chronic neuropathic pain. Therefore, this study identifies a neuro-glial interaction that mediates chronic pain in supraspinal brain.