The serine/threonine kinase Akt, or protein kinase B (PKB) lies in the crossroads of multiple cellular signaling pathways and acts as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI 3-kinase). In our previous study, we found that PKB/Akt contributes to mechanical hypersensitivity both in spinal cord and periphery. The central sensitization of nociceptive dorsal horn neurons underlies the development of secondary mechanical hypersensitivity. In this study, we use electrophysiological approaches to investigate whether the PKB/Akt in spinal cord is involved in the sensitization of wide dynamic range (WDR) dorsal horn neuron induced by capsaicin. We used microdialysis method to infuse the drug to dorsal spinal cord. The background activity and the responses to innocuous and noxious stimuli of WDR neuron were observed. We found that the background activity and the response to noxious stimuli of WDR neuron significantly increased after intradermal injection of capsaicin. However, SH-6, a PKB/Akt inhibitor pretreatment significantly prevent the sensitization of WDR neuron induced by capsaicin. SH-6 has no effect on the baseline activity of WDR neuron. Collectively, the results suggest that PKB/Akt is involved in the sensitization of WDR dorsal horn neuron induced by noxious stimulation. (Supported by NIH grants NS09743 and NS11255)