Figure 11

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.