To judge the result of PI3K and PKB/Akt service on the established neuropathic suffering, the intrathecal injection of wortmannin and Akt inhibitor IV was developed on day 3, day 1 and day 7 after L5 SNL in another three groups of animals, respectively. The outcomes confirmed that the mechanical allodynia and thermal hyperalgesia were plainly alleviated in these rats that received the wortmannin therapy starting at the 1st and the 3rd day, but not at the 7th day, after L5 SNL. Whereas post-treatment with Akt chemical IV as above, the significant inhibitory effect on the neuropathic discomfort behaviors only was seen in the mice that received the drug treatment started at the 1st day after L5 Doxorubicin Adriamycin SNL. We conducted immunofluorescence staining of r PKB/Akt in ipsilateral L5 DRG and L5 spinal cord after the rats had received wortmannin intrathecal injection for 4 days and 2 days, respectively, to verify the result of PI3K about the activation of PKB/Akt after L5 SNL. Weighed against vehicle team, wortmannin treatment significantly decreased the percentage of p PKB/Akt IR positive neurons in DRG, and the percentage of p PKB/Akt IR positive place in L5 spinal dorsal horn. We found a vital position for the activation of PKB/ and PI3K Akt in the Lymphatic system development of neuropathic pain caused by L5 SNL in the present study. Our information showed that L5 SNL induced clear activation of PKB/Akt in ipsilateral L5 and L4 DRG neurons and in L5 spinal dorsal horn. Intrathecal injection of PI3K certain inhibitor wortmannin or LY294002 and PKB/Akt inhibitor Akt inhibitor IV or Deguelin, started before surgery, reduced the thermal hyperalgesia and mechanical allodynia following L5 SNL. Intraperitoneal injection of wortmannin and Deguelin as above also paid off the pain hypersensitivity. Post-treatment with wortmannin, began at the first day or even the 3rd day, but not at the 7th day, after L5 SNL, decreased the unusual pain behaviors. While post-treatment with Akt chemical IV only began at the 1st day after surgery discovered the inhibitory effect to the pain related actions. Immunohistochemistry confirmed that intrathecal injection of wortmannin significantly inhibited the activation of PKB/Akt in L5 DRG and L5 spinal dorsal horn induced order MK-2206 by L5 SNL. It proposed that the PI3K and PI3K PKB/Akt sign path activation may donate to the development of neuropathic pain at an early stage. PI3K and PI3K PKB/Akt transmission pathway is normally activated by some neurotrophin in addition to other physiological stimuli. It has been implicated in various cellular functions, including angiogenesis, transcription, apoptosis, expansion, migration and glucose kcalorie burning involved in the activation of PI3K o-r PI3K PKB/Akt transmission path.