Schematic representation of the possible mechanisms of PTEN involvement in neuropathic pain. (A) Peripheral nerve injury could downregulate the spinal astrocytic PTEN, which leads to the upregulation of phospho-mTOR and TNF-α and results in neuroinflammation and nociceptive sensitization. In addition, spinal microglia-astrocyte interactions also promote nociceptive responses. (B) Through the upregulation of spinal astrocytic PTEN by i.t. Ad-PTEN, peripheral nerve injury-induced upregulation of phospho-mTOR and TNF-α is inhibited, thereby inhibiting neuroinflammation and nociceptive sensitization. The effect of the upregulation of spinal PTEN by i.t. Ad-PTEN on attenuating peripheral nerve injury-induced microglial activation may be through suppressing the astrocyte-microglia interaction by reducing the astrocytic mediator TNF-α. Ad-PTEN, adenovirus-mediated phosphatase and tensin homolog deleted from chromosome 10; p-mTOR, phosphorylated mammalian target of rapamycin; TNF, tumor necrosis factor.