Background: In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2 MAPK and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. This study was conducted to determine if low dose ketamine had an effect on the activation of ERK 1/2 and CREB in the development of neuropathic pain. Methods: This study was conducted to evaluate ERK 1/2 and CREB protein in a sham operated (control) group, neuropathic pain and normal saline (NP+NS) group and neuropathic pain and ketamine (NP+Keta) group. To accomplish this, male Sprague-Dawley rats were anesthetized and then subjected to L5-L6 spinal nerve ligation (SNL, neuropathic rats). The total amounts of ERK 1/2 and CREB protein were then assessed by western blot analysis. In addition, changes in the amounts of ERK 1/2 and CREB mRNA were evaluated by RT-PCR. Results: There was a significant increase in the amount of ERK 1/2 and CREB in the NP+NS group when compared with the sham group. However, the amount of ERK 1/2 and CREB protein induced due to SNL were significantly reduced by continuous infusion with ketamine in the NP+Keta group. Conclusions: The results of this study revealed a positive linkage between NMDA receptors and the ERK-CREB signaling pathway. Therefore, NMDA receptors could be the target of future therapeutic approaches. Additionally, the results of the present study provide additional evidence that low dose ketamine effectively prevents and treats central neuropathic pain following SNL. (Korean J Anesthesiol 2009;57:210∼6)