In the nervous system, the PI3K PKB/Akt signal process is activated by growth factors, hormones, o-r neurotransmitters, and participates in cellular exercise that underlies development. Adequate and increasing evidence suggests the PI3K PKB/Akt process is associated with synaptic plasticity such as long term potentiation, long term melancholy and brain derived neurotrophic factor dependent spatial memory formation. Recently, it has been reported that the PI3K and PI3K PKB/Akt path activation mediates the thermal hyperalgesia induced by capsaicin o-r by intradermal injection of NGF, and there is an activity dependent phosphorylation of PKB/Akt in DRG neurons of adult rats. While whether an immediate injury to peripheral buy CAL-101 nerve also induced the activation of PKB/Akt and PI3K in pain related path still remains unexplored. Employing a pain model of L5 SNL, we discovered that PKB/Akt was obviously activated in primary afferent neurons of L4 and L5 DRG, specially in IB4 good little nociceptive neurons, started at 1-2 h after surgery and lasted to the 3rd day. At same time, L5 SNL also induced PKB/Akt activation in ipsilateral L5 spinal dorsal horn from day 1 to day 7 after operation. As the p PKB/Akt is normally Lymph node referred while the sign of PI3K activation, so we further observed the effect of wortmannin, an effective inhibitor of PI3K, to the activation of PKB/Akt in DRG and back after L5 SNL. The outcome showed that wortmannin treatment for 2 days significantly reduced the size of the p PKB/Akt level in L5 DRG. The PKB/Akt activation in L5 spinal dorsal horn was also inhibited by wortmannin therapy for 4 days. It suggested that treated subjects with wortmannin in the manner of current study successfully inhibited the activation of PKB/Akt in DRG and back. It also confirmed the previous research the PKB/Akt may be the downstream effector of PI3K activation. Very recently, several groups noted that intradermal injection of capsaicininduced PKB/Akt service in primary afferent buy Celecoxib started as soon as 5 min and maintained for more than 1 h after the therapy, and wortmannin efficiently blocks the capsaicininduced increase of p PKB/Akt degree. Therefore the answers are in line with our present finding that inhibited the PI3K effectively prevented the activation of PKB/Akt after L5 SNL. But the different time course of PKB/Akt service between our research with that of Zhuang and Sun had reported may be as a result of different pain types used. Previous studies have shown that Wallerian degeneration following axotomy contributes to the development of neuropathic pain via production of cytokines and nerve growth factors. One of them, TNF, IL 1 and NGF have already been proven to play an important role for the suffering hypersensitivity following nerve injury.